Advertisement

Confronting Racism in All Forms of Pain Research: Reframing Study Designs

Published:February 25, 2022DOI:https://doi.org/10.1016/j.jpain.2022.01.010

      Highlights

      • Pain research that seeks to create pain care equity uses an antiracism framework.
      • An antiracism framework requires self-reflection on study design choices.
      • Examples of antiracism reframes for common study design factors are provided.

      Abstract

      This second paper in a 3-part series on antiracism in pain research across the translational spectrum focuses on study design factors. Although objectivity is a cornerstone value of science, subjectivity is embedded in every step of the research process as investigators make choices about who they collaborate with, which research questions they ask, how they recruit participants, which research tools they use, and how they analyze and interpret data. We present theory and evidence from disciplines such as sociology, medical anthropology, statistics, and public health to discuss 4 common study design factors, including 1) the dominant biomedical narrative of pain that restricts funding and exploration of social indicators of pain, 2) low diversity and inclusion in pain research enrollment that restricts generalizability to racialized groups, 3) the use of “race” or “ethnicity” as a statistical variable and proxy for lived experiences (eg, racism, resilience), and 4) limited modeling in preclinical research for the impact of social factors on pain physiology. The information presented in this article is intended to start conversations across stakeholders in the pain field to explore how we can come together to adopt antiracism practices in our work at large to achieve equity for racialized groups.

      Perspective

      This is the second paper in a 3-part series on antiracism in pain research. This part identifies common study design factors that risk hindering progress toward pain care equity. We suggest reframes using an antiracism framework for these factors to encourage all pain investigators to collectively make strides toward equity.

      Key words

      Across healthcare fields, scholars have called for a shift toward antiracism in research praxis to achieve health equity.
      • Crear-Perry J
      • Maybank A
      • Keeys M
      • Mitchell N
      • Godbolt D
      Moving towards anti-racist praxis in medicine.
      ,
      • Ford CL
      • Airhihenbuwa CO
      Critical race theory, race equity, and public health: Toward antiracism praxis.
      ,
      • Noltemeyer A
      • Grapin SL
      Working Together Towards Social Justice, Anti-racism, and Equity: A Joint Commitment From School Psychology International and Journal of Educational and Psychological Consultation.
      ,
      • Truong M
      • Sharif MZ
      We’re in this together: A reflection on how bioethics and public health can collectively advance scientific efforts towards addressing racism.
      This shift calls on us to challenge the fundamental values of science and recognize the historical influences that still loom large over the research enterprise, including the field of pain. One of the fundamental values in science is objectivity.
      • Gordon KR
      Objectivity in science.
      Consequently, researchers often aim to keep their scientific endeavors separate from their personal beliefs (eg, dissociating their role as a scientist from their role as an advocate for patients). Subjectivity, however, is embedded in every step of the research process
      • Williams DR
      • Sternthal M
      Understanding racial-ethnic disparities in health: Sociological contributions.
      – from the choices we make in identifying and conceptualizing scientific questions, designing a study's methods, and describing findings in scientific narratives – making true objectivity in science unattainable. Additionally, advocacy is inherent in all pain research that strives to improve the quality of care and eliminate individuals’ suffering from pain. Our call for a shared commitment to antiracism in pain research is simply an expansion of this existing advocacy so that it actively includes the pain care needs of marginalized communities that have been ignored in our work at large.
      The present article is the second paper in a 3-part series on antiracism in pain research (see Morais et al
      • Morais C
      • Aroke EN
      • Letzen JE
      • Campbell CM
      • Hood AM
      • Janevic MR
      • Mathur VA
      • Merriwether EN
      • Goodin BR
      • Booker SQ
      • Campbell LC
      Confronting Racism in Pain Research: A Call to Action.
      and Hood et al
      • Hood AM
      • Booker SQ
      • Morais CA
      • Goodin BR
      • Letzen JE
      • Campbell LC
      • Merriwether EN
      • Aroke EN
      • Campbell CM
      • Mathur VA
      • Janevic MR
      Confronting racism in pain research: A shared commitment for engagement, diversity, and dissemination.
      for the first and third papers in the series, respectively). We first define key terms that will help investigators adopt an antiracism framework for their research. Second, we discuss concerns related to the tension between subjectivity/advocacy and science. Third, we describe preclinical and clinical study design elements identified by the Antiracism CoaliTION in Pain Research (ACTION-PR) and discussed with 39 pain disparities experts in think tanks held in the Fall of 2020 (see Morais et al
      • Morais C
      • Aroke EN
      • Letzen JE
      • Campbell CM
      • Hood AM
      • Janevic MR
      • Mathur VA
      • Merriwether EN
      • Goodin BR
      • Booker SQ
      • Campbell LC
      Confronting Racism in Pain Research: A Call to Action.
      for details). Topics addressed in this article include: 1) the dominant biomedical metanarrative of pain, 2) significant underrepresentation of study participants from racialized groups, 3) the use of “race”/ethnicity as a statistical variable, and 4) limited modeling of social factors’ impact on pain physiology in preclinical studies. Finally, we provide example methods and scenarios to reframe these study design choices to be consistent with an antiracism framework.

      Key Definitions

      Language shapes individuals’ world views.

      Kelly N, Zetzsche JO: Found in translation: How language shapes our lives and transforms the world. TarcherPerigee; 2012.

      ,
      • Rickford JR
      Raciolinguistics: How Language Shapes Our Ideas About Race.
      Shifting from language that blames individuals to language that holds systems of oppression accountable is a foundational step in the shift toward antiracism in pain research (see Hood et al
      • Hood AM
      • Booker SQ
      • Morais CA
      • Goodin BR
      • Letzen JE
      • Campbell LC
      • Merriwether EN
      • Aroke EN
      • Campbell CM
      • Mathur VA
      • Janevic MR
      Confronting racism in pain research: A shared commitment for engagement, diversity, and dissemination.
      for a detailed explanation) Table 1 defines 5 commonly used terms or approaches in research, provides suggested paradigm shifts, and explains the rationale for these shifts. There are 2 notable replacement terms (ie, racialized groups and social indicators of health) used throughout the present article and warrant additional explanation below.
      Table 1Explanations of Common Language Choices in Scientific Narratives and a Commonly Used Underlying Research Framework in Pain Research With Proposed Shifts Based on an Antiracism Framework
      Common approachProposed shift
      Because semantic change occurs continually, the utility of these proposed shifts should be closely monitored over time. As needed, new terms that hold systems accountable and validate the experiences of racialized individuals should be used.
      Rationale for shift
      Key termDefinitionKey termDefinition
      Common underlying research framework
      NonracismThe passive rejection, opposition, and disassociation from behaviors, discourses, and ideologies that are considered racistAntiracismThe active process of eliminating racism by changing systems, organizational structures, policies and practices, and attitudes, so that power is redistributed and shared equitablyCalls on investigators to actively build cultural humility, self-reflect on study design choices, and engage in power-sharing and other behaviors that will bring the field of pain closer to justice for racialized groups
      Common Language Choices in Scientific Narratives
      Race/RacialSocial classification of individuals based on a mix of physical features (eg, skin tone and hair texture)Racialized identity or racialized group identity when referring to racialized groups; “Race” (in quotations) when referring to White people or the general constructA social process by which racialized meaning is ascribed to a group of individuals that previously did not identify as such; historically, White Europeans racialized individuals who did not have similar physical features to their own, leading to "othering" and differential treatment; because White people initiated the process of racialization, in our series, we do not refer to White people as being racializedIndicates the action of White European societal and structural influences in creating and perpetuating racialized groups and hierarchies based on those groups (ie, acknowledges the sociopolitical process) rather than implying distinct classes of people (ie, might be inferred as biologically based); We use quotation marks around the term “race” where relevant to connote that it is a socially constructed, dynamic phenomenon
      MinorityA distinct group that coexists with, but is subordinate to, a more dominant groupMinoritizedGroup(s) in society that are defined as "minorities" by a dominant groupWhile used by some to denote minority percentage of the population, this term has taken on connotation that that racialized groups are relegated to a "minority" status by White dominant society
      Social Determinants of HealthThe conditions in the environments where people are born, live, work, play, and age that affect health, functioning, and quality of life that ultimately lead to poor health outcomesSocial Indicators of HealthAn imperfect replacement term that seeks to emphasize social factors that contribute to health outcomes while moving away from deterministic language (see Salerno & Bogard, 2019)Indicates that conditions are not fixed and can change across the lifespan, be surpassed because of resilience factors, or change with intervention
      People of Color, BIPOC, non-WhiteNaming conventions typically used to refer to racialized groupsUse individuals' preferred identities or "racialized group(s)"For example, "Black" or "African American" or "Jamaican American" when referring to a particular identity; "Racialized groups" can be used when referring to individuals spanning more than 1 panethnic categoryRather than passively cluster panethnic identities – which erases their heterogeneity – using individuals' preferred identity is a step toward recognizing unique lived experiences, and using "racialized" actively acknowledges the reason for lumping these groups together
      Abbreviation: BIPOC, Black, Indigenous, People of Color.
      low asterisk Because semantic change occurs continually, the utility of these proposed shifts should be closely monitored over time. As needed, new terms that hold systems accountable and validate the experiences of racialized individuals should be used.
      When referring to groups facing societal oppression based on physical characteristics associated with the construct of “race,” this series uses the term racialized groups. Racialization occurs when individuals create social groupings to differentiate among individuals with physical characteristics and/or other perceived behavioral traits that are similar to or different from their own.
      • Hochman A
      Racialization: A defense of the concept.
      Historically, White Europeans racialized individuals who did not have similar physical features to their own as a way of “othering” and ascribing these groups’ inferior positions in society. Evolving “race” categories on the US Census over time demonstrates that racialization is a dynamic, sociopolitical process. Shifting from terms such as people of color to racialized groups emphasizes the action of 1 group's societal oppression of another and is intentional language for why diverse, panethnic communities are grouped together in discussion. Racism is a dominant form of social oppression that impacts racialized groups in Western, educated, industrialized, rich, and democratic (WEIRD) countries. In the Global South, other factors such as colorism, ethnicity, religion, caste, etc., are used to oppress groups. Although this article focuses on racism and its impact on the pain experiences of racialized groups, the study design factors and reframes discussed below are still relevant to how investigators in the Global South can change their work to benefit oppressed groups in their particular society.
      Further, this article reviews foundational theory and evidence to emphasize the need to research the social factors that influence pain. Social determinants of health (SDoH) is a term used by the World Health Organization and US Center for Disease Control to describe the causal effect of social and environmental conditions on health.
      • Braveman P
      • Gottlieb L
      The social determinants of health: It's time to consider the causes of the causes.
      A determinant has been defined as “a determining factor or agent; a ruling antecedent, a conditioning element; a defining word or element.”

      Dictionary OE: “determinant, adj. and n.”. Available at: https://www.oed.com/view/Entry/51232?redirectedFrom=determinant 2022. Accessed March 1, 2021.

      Although the term SDoH has been applied to refer to both mutable and immutable factors,
      • Walker RJ
      • Smalls BL
      • Egede LE
      Social determinants of health in adults with type 2 diabetes–Contribution of mutable and immutable factors.
      it has been criticized for implying fixedness of social/environmental conditions and de-emphasizing the protective role of resilience.
      • Salerno J
      • Bogard K
      What do social determinants of health determine?.
      This series uses social indicators of health as an imperfect step away from deterministic language, given that an indicator has been defined as “anything used in a scientific experiment to indicate the presence of a substance or quality.”

      Dictionary OE: “indicator, n.” Available at: https://www.oed.com/view/Entry/94420?redirectedFrom=indicator 2022. Accessed March 1, 2021.

      No substitute term for SDoH has yet been universally adopted, and we encourage suggestions for an updated term that emphasizes that social/environmental conditions can change across the lifespan, respond to interventions, or be mitigated through resilience factors (eg, social contributors to pain, social predictors of pain, etc.).

      Subjectivity and Advocacy in Science

      Subjectivity and advocacy are often considered sources of bias in science. Underlying this concern is the aspiration for science to be fundamentally devoid of these factors and that introducing subjectivity and advocacy into the research process will influence findings. However, subjectivity and advocacy are inextricable components of science. For example, studies examining peer reviewer agreement highlight the subjective nature of science; inconsistency in ascribing strengths and weaknesses to grant applications among reviewers cannot solely be explained by variability in scale use.
      • Fogelholm M
      • Leppinen S
      • Auvinen A
      • Raitanen J
      • Nuutinen A
      • Väänänen K
      Panel discussion does not improve reliability of peer review for medical research grant proposals.
      ,
      • Pier EL
      • Brauer M
      • Filut A
      • Kaatz A
      • Raclaw J
      • Nathan MJ
      • Ford CE
      • Carnes M
      Low agreement among reviewers evaluating the same NIH grant applications.
      An antiracism framework acknowledges that 1) subjectivity is embedded in the research process, and 2) advocacy makes our work more meaningful to patients and advances health equity.
      First, as an example of subjectivity in data collection, consider the 1790–1810 iterations of the US Census, a decennial survey used to count the US population. During the US's establishment, delegates sought to collect “objective” data on the number of inhabitants within districts to apportion political representation.
      • Riche MF
      Cultural and political dimensions of the U.S. census: Past and present.
      They faced several study design choices, including: 1) how do household members get enumerated? and 2) what is the value of each enumeration? They decided that designated Census enumerators would determine the number of members in each household. Enumerators would code each household member using “race” categories, including “free” persons and “slaves” (applied to Black individuals who were enslaved).
      • Pratt B
      • Hixson L
      • Jones N
      Measuring Race and Ethnicity Across the Decades: 1790-2010.
      Finally, they decided that “free” persons would count as 1 household member, Indigenous individuals would not be included in counts, and “slaves” would count as three-fifths of a household member.

      congress.gov: US Constitution: Article I, section 2, clause 3. Available at: https://constitution.congress.gov/browse/essay/artI_S2_C3_1/ 2022. Accessed March 1, 2021.

      These subjective design choices resulted in “objective” data that helped entrench systemic racism in US society. To this day, aspects of the current Census’ design result in “objective” data that adversely impact racialized groups (eg, prison gerrymandering,
      • Stachulski F
      Prison gerrymandering: Locking up elections and diluting representational equality.
      debate over adding a citizenship question
      • Berry-James RM
      • Gooden ST
      • Johnson III, RG
      Civil rights, social equity, and census 2020.
      ).
      Second, advocacy has been successfully infused into research to improve health equity by pushing for changes in established methods. For example, although cardiovascular disease is one of the leading causes of death worldwide, a societal misperception was that it mostly affects cisgender men. One key driver of this misperception was the prevailing research, which only used male mice/cells or cisgender human men. Scientists highlighted the danger of underdiagnosing cardiovascular disease symptoms among cisgender women.
      • Correa-De-Araujo R
      Serious gaps: How the lack of sex/gender-based research impairs health.
      ,
      • Kim AM
      • Tingen CM
      • Woodruff TK
      Sex bias in trials and treatment must end.
      With research findings that had poor generalizability to cisgender women, calls were made for biomedical research to consider assigned sex at birth and gender identity in study designs. Ultimately, this advocacy led to the creation of policies that include sex- and gender-based analyses in study designs from the US National Institutes of Health, Canadian Institutes of Health Research, and the European Research Council.
      • White J
      • Tannenbaum C
      • Klinge I
      • Schiebinger L
      • Clayton J
      The integration of sex and gender considerations into biomedical research: Lessons from international funding agencies.
      Although future work is needed to understand the presentation of cardiovascular disease symptoms among transgender and gender diverse individuals, this example shows that advocacy does not diminish the rigor or objectivity of science. On the contrary, it improves its rigor, generalizability, and importance.
      An antiracism framework encourages researchers to embrace the subjectivity and advocacy that already exists in science. By embracing these factors, researchers can engage in critical self-reflection on how our training and sociocultural worldview feed into our subjective design choices and who is included in our advocacy. Organizations, such as the US National Pain Advocacy Center and Global Alliance of Partners for Pain Advocacy, exist for the very purpose of bringing together scientists, clinicians, policy makers, and patients to advocate for evidence-based policies that yield equitable pain care.
      Our call for a shared commitment to antiracism in pain research aligns with previous efforts to address health inequities. Whereas nonracism refers to passive opposition to ideologies and behaviors that perpetuate racialized inequities,
      • King L
      Black History as Anti-Racist and Non-Racist BT - But I Don’t See Color.
      antiracism refers to ideologies and behaviors that affirm and seek to enable equity across groups.
      • Bonnett A
      The Americanisation of anti-racism? Global power and hegemony in ethnic equity.
      Ongoing antiracism education, cultural humility, and self-reflection on how the investigative team's actions might perpetuate pain inequities are foundations for antiracism in pain research praxis and can be implemented at every career stage and data collection milestone. As discussed in Morais et al,
      • Morais C
      • Aroke EN
      • Letzen JE
      • Campbell CM
      • Hood AM
      • Janevic MR
      • Mathur VA
      • Merriwether EN
      • Goodin BR
      • Booker SQ
      • Campbell LC
      Confronting Racism in Pain Research: A Call to Action.
      the ACTION-PR intentionally calls for a shared commitment to antiracism rather than guiding principles or regulations. The study design factors and reframes discussed below should not be interpreted as fixed, all-inclusive guidelines or rules, nor are we suggesting that certain study designs should be “forbidden.” Our suggestions are not “all-or-nothing” (ie, they are not intended to suggest that only studies that incorporate all reframes are considered “antiracist”). Instead, the reframes are proposed as a compass for investigators who are committed to improving pain care for marginalized groups and highlight potential areas for growth and change from current dogma. For some researchers, certain reframes proposed below might replace their current practices. For others, these reframes might lead to studies that complement their existing work. We view these study design factors and reframes as starting points for investigators to consider; importantly, the suggestions for antiracism research praxis throughout this series should be revisited regularly to determine their utility.

      Study Design Factor 1: A Dominant Biomedical Metanarrative of Pain Eclipses Research on the Social Indicators of Pain

      Metanarratives are overarching theories or interpretations of circumstances that structure people's beliefs.
      • Lyotard J-F
      The Postmodern Condition: A Report on Knowledge.
      In medicine, metanarratives 1) center on understanding mechanisms of health and disease, 2) are informed by foundational publications, conference proceedings, and/or providers’ case examples, and 3) drive the direction of funding priorities and subsequent research efforts.
      • Kalitzkus V
      • Matthiessen PF
      Narrative-based medicine: Potential, pitfalls, and practice.
      ,
      • Schrewe B
      From history to myth: Productive engagement with the Flexnerian metanarrative in medical education.
      Hansen et al
      • Hansen H
      • Parker C
      • Netherland J
      Race as a ghost variable in (white) opioid research.
      importantly describe how they can also lead to normalized, embedded practices in research that maintain health inequities. In the field of pain, metanarratives in the 19th and 20th centuries applied a traditional biomedical framework to explain pain as a phenomenon solely caused by pathophysiologic and biochemical processes.
      • Gatchel RJ
      • Peng YB
      • Peters ML
      • Fuchs PN
      • Turk DC
      The biopsychosocial approach to chronic pain: Scientific advances and future directions.
      Although the biopsychosocial model of pain
      • Engel GL
      The need for a new medical model: A challenge for biomedicine.
      ,
      • Turk DC
      • Monarch ES
      Biopsychosocial Perspective on Chronic Pain.
      is now broadly accepted, the biomedical metanarrative of pain is still prioritized in our field. For example, across 3 workshops dedicated to developing funding priorities for the US National Institutes of Health (NIH) Helping End Addiction Long-Term (HEAL) Initiative in 2017, attendees identified medication development for opioid use disorder, nonaddictive pain treatments, and neurobiological pain mechanisms as key areas to allocate funds. As a response to feedback on this initial biomedical emphasis, the NIH Office of Behavioral and Social Sciences Research later worked to develop social and behavioral HEAL funding opportunities for fiscal year 2019.
      • Riley WT
      • Greene-Schloesser D
      • Blachman-Demner DR
      • Spittel M
      Twenty-five years of the national institutes of health office of behavioral and social sciences research.
      This example highlights an important drawback to a dominant biomedical metanarrative – it minimizes the importance of psychosocial factors in the pain experience, in turn funneling funding to biomedically-focused studies as a field norm. Our intent in describing this drawback is not to criticize or minimize the numerous, critical contributions from biomedical pain research. However, we cannot deny that it has predominantly enrolled middle-class, non-Hispanic White (NHW) participants from WEIRD countries, inadvertently prioritizing the pain experiences of this sociodemographic group and limiting our knowledge of systematic factors that impact pain experiences beyond this group.
      WEIRD society's structures inequitably benefit White individuals and disenfranchise racialized groups. Globally, social oppression – which may be based on a number of intersecting factors, including colorism, caste systems, and religion – are the drivers of inequities. The experiences of racism, social oppression, and/or political exclusion are chronically stressful. The physiological effects of these factors have been documented in other health fields, including increases in cortisol, changes in neurophysiology, and increased risk of DNA methylation (epigenetic changes).
      • Adam EK
      • Heissel JA
      • Zeiders KH
      • Richeson JA
      • Ross EC
      • Ehrlich KB
      • Levy DJ
      • Kemeny M
      • Brodish AB
      • Malanchuk O
      • Peck SC
      • Fuller-Rowell TE
      • Eccles JS
      Developmental histories of perceived racial discrimination and diurnal cortisol profiles in adulthood: A 20-year prospective study.
      ,
      • Barcelona de Mendoza V
      • Huang Y
      • Crusto CA
      • Sun Y V
      • Taylor JY
      Perceived Racial Discrimination and DNA Methylation Among African American Women in the InterGEN Study.
      ,
      • Bell KA
      • Kobayashi I
      • Akeeb A
      • Lavela J
      • Mellman TA
      Emotional response to perceived racism and nocturnal heart rate variability in young adult African Americans.
      ,
      • Harrell CJP
      • Burford TI
      • Cage BN
      • Nelson TM
      • Shearon S
      • Thompson A
      • Green S
      Multiple pathways linking racism to health outcomes.
      ,
      • Paradies Y
      • Ben J
      • Denson N
      • Elias A
      • Priest N
      • Pieterse A
      • Gupta A
      • Kelaher M
      • Gee G
      Racism as a determinant of health: A systematic review and meta-analysis.
      ,
      • Sullivan S
      Inheriting racist disparities in health: Epigenetics and the transgenerational effects of white racism.
      Without considering the influence of social factors on physiological and psychological processes in a biopsychosocial model, the biomedical metanarrative risks that the field will develop pain biomarkers and treatments that do not apply to socially and politically oppressed groups, exacerbating pain inequities. Further, a biomedical metanarrative conflates “race” with genetic ancestry and explains racialized pain disparities as arising from biological – rather than sociopolitical – factors.
      • Roberts D
      Fatal Invention: How Science, Politics, and Big Business Re-create Race in the Twenty-First Century.

      Antiracism Reframe 1: Design Studies that Reflect a Biopsychosocial Metanarrative of Pain

      Study designs following a biopsychosocial metanarrative of pain consider how interactions among biological, psychological, and social factors contribute to pain outcomes. Psychological components of pain and their interaction with biological functions have been increasingly represented in pain research since the biopsychosocial model was proposed; however, concerted efforts across the field to integrate social indicators of health have lagged. Social indicators of health are considered the “upstream” causes
      • Gehlert S
      • Sohmer D
      • Sacks T
      • Mininger C
      • McClintock M
      • Olopade O
      Targeting health disparities: A model linking upstream determinants to downstream interventions.
      of health disparities that fall along sociopolitically constructed categories. To paraphrase critical scholars, disparities in health are “biological reflections of social inequality.”
      • Herrick C
      • Bell K
      Concepts, disciplines and politics: On ‘structural violence’ and the ‘social determinants of health.’.
      ,
      • Plaut VC
      Diversity science: Why and how difference makes a difference.
      Social indicators are shaped by power structures and result in the avoidable and inequitable distribution of disease burden to members of minoritized groups.
      • Braveman PA
      • Kumanyika S
      • Fielding J
      • Laveist T
      • Borrell LN
      • Manderscheid R
      • Troutman A
      Health disparities and health equity: The issue is justice.
      ,
      • Marmot M
      • Wilkinson R
      Social Determinants of Health.
      Examples of such conditions that have the potential to change across the lifespan include economic instability, limited education opportunities, reduced healthcare access, unfavorable neighborhood conditions, lack of community support, and discriminatory interpersonal exchanges.
      When social indicators of pain have been considered to date, they have largely been conceptualized on an individual or interpersonal level (eg, provider bias)
      • Blyth FM
      • Macfarlane GJ
      • Nicholas MK
      The contribution of psychosocial factors to the development of chronic pain: The key to better outcomes for patients?.
      ,
      • Karran EL
      • Grant AR
      • Moseley GL
      Low back pain and the social determinants of health: A systematic review and narrative synthesis.
      and much less work has been done to understand community and societal conditions. As demonstrated in the US National Institute of Minority Health and Health Disparities (NIMHD) Research Framework, social indicators of health operate at various levels (ie, individual, interpersonal, community, and societal) and domains (ie, biological, behavioral, physical/built environment, sociocultural environment, healthcare system) of influence. Given this multidimensionality, an antiracism framework in pain research still considers biological and psychological factors as important contributors to pain experiences and treatment responses across humans. However, it holds that racialized pain disparities arise from the impact of social indicators (ie, racism) on biological/psychological factors and rejects the notion that they arise from innate differences in genetics/biology or stereotyped group traits. In other words, it sees racism as the fundamental cause of racialized pain inequities. Shifting from a biomedical metanarrative to one that considers how social indicators interact with biological and psychological factors presents new opportunities for uncovering pain mechanisms for a diverse population beyond middle-class, NHW individuals in WEIRD societies.
      An example of this reframe applies to the way metanarratives drive our conceptualization of sickle cell disease (SCD). SCD is the most common genetic disorder worldwide that can affect all individuals but has the highest prevalence among individuals of African ancestry.
      • Campbell AD
      • Colombatti R
      • Andemariam B
      • Strunk C
      • Tartaglione I
      • Piccone CM
      • Manwani D
      • Asare EV
      • Boruchov D
      • Farooq F
      An analysis of racial and ethnic backgrounds within the CASiRe International Cohort of sickle cell disease patients: Implications for disease phenotype and clinical research.
      A Eurocentric biomedical metanarrative often occurs, which conflates the heredity of SCD that is based on genetic ancestry with racialized identity to explain SCD as a condition that “affects Black people” and has been used by some to argue the existence of biological races. An antiracism reframe using a biopsychosocial metanarrative separates racialized identity from ancestry to understand that sickle cell trait served as a protective function in areas where malaria is endemic (eg, sub-Saharan Africa, India)
      • Cyrklaff M
      • Sanchez CP
      • Kilian N
      • Bisseye C
      • Simpore J
      • Frischknecht F
      • Lanzer M
      Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes.
      ,
      • Esoh K
      • Wonkam A
      Evolutionary history of sickle-cell mutation: Implications for global genetic medicine.
      and that people from these regions are racialized in WEIRD countries or experience colorism in the Global South. In WEIRD countries, individuals with SCD who are racialized as Black face the burden of a history of colonization, enslavement, and/or segregation with ongoing social practices that limit access to healthcare, impact psychological wellbeing, and maintain disparities.
      • Farooq F
      • Mogayzel PJ
      • Lanzkron S
      • Haywood C
      • Strouse JJ
      Comparison of US federal and foundation funding of research for sickle cell disease and cystic fibrosis and factors associated with research productivity.
      ,
      • Fraiman YS
      • Wojcik MH
      The influence of social determinants of health on the genetic diagnostic odyssey: Who remains undiagnosed, why, and to what effect?.
      ,
      • Power-Hays A
      • McGann PT
      When actions speak louder than words — Racism and sickle cell disease.
      Inequities in SCD prevalence and care due to social oppression is also observed within India, wherein people from socioeconomically disadvantaged castes – often ranked as such due to skin color – are most burdened.
      • Hockham C
      • Bhatt S
      • Colah R
      • Mukherjee MB
      • Penman BS
      • Gupta S
      • Piel FB
      The spatial epidemiology of sickle-cell anaemia in India.
      An antiracism reframe further considers institutional forces, such as funding disparities that decrease research productivity and limit novel drug development for the SCD population compared to nonracialized health conditions (eg, cystic fibrosis).
      • Farooq F
      • Mogayzel PJ
      • Lanzkron S
      • Haywood C
      • Strouse JJ
      Comparison of US federal and foundation funding of research for sickle cell disease and cystic fibrosis and factors associated with research productivity.
      Due to the broad effects of racism, social indicators covary, are interdependent, and tend to be mutually reinforcing across time.
      • Gee GC
      • Hing A
      • Mohammed S
      • Tabor DC
      • Williams DR
      Racism and the life course: Taking time seriously.
      For the latter reason, research across the translational spectrum on the social indicators of pain would be further advanced by understanding individuals’ lived experiences across the lifespan. Preliminary evidence suggests that the accumulation of social injustice is associated with enhanced laboratory and clinical pain
      • Brooks Holliday S
      • Dubowitz T
      • Ghosh-Dastidar B
      • Beckman R
      • Buysse D
      • Hale L
      • Buman M
      • Troxel W
      Do sleep and psychological distress mediate the association between neighborhood factors and pain?.
      ,
      • Mathur VA
      • Kiley KB
      • Haywood C
      • Bediako SM
      • Lanzkron S
      • Carroll CP
      • Buenaver LF
      • Pejsa M
      • Edwards RR
      • Haythornthwaite JA
      • Campbell CM
      Multiple levels of suffering: Discrimination in health-care settings is associated with enhanced laboratory pain sensitivity in sickle cell disease.
      ,
      • Mathur VA
      • Trost Z
      • Ezenwa MO
      • Sturgeon JA
      • Hood AM
      Mechanisms of injustice: What we (don’t) know about racialized disparities in pain.
      ,
      • Ong AD
      • Goktas S
      • Carrington Reid M
      More than hurt feelings: The wear and tear of day-to-day discrimination in adults with chronic pain.
      ,
      • Waller R
      • Smith AJ
      • O'Sullivan PB
      • Slater H
      • Sterling M
      • Straker LM
      The association of early life stressors with pain sensitivity and pain experience at 22 years.
      ,
      • You DS
      • Albu S
      • Lisenbardt H
      • Meagher MW
      Cumulative childhood adversity as a risk factor for common chronic pain conditions in young adults.
      (potentially through increased allostatic load burden), but there remains a gap in understanding how changes in social indicators from childhood to adulthood influence trajectories of pain and its psychological/biological predictors.
      • Rassu FS
      • Luedke JC
      • Nanavaty N
      • Mathur VA
      • Meagher MW
      Greater mechanical temporal summation of pain in Latinx-Americans and the role of adverse life experiences.
      Scholars criticizing research on the social indicators of health have noted that this work is often unable to be tested in causal paradigms and that it is ideologically motivated.
      • Glymour MM
      • Hamad R
      Causal thinking as a critical tool for eliminating social inequalities in health.
      The field's ability to robustly reframe pain research questions in the context of a biopsychosocial metanarrative, then, first calls on investigators, reviewers, editors, and clinicians to acknowledge the abundant literature documenting the sociopolitical, historical, and physical environmental influences on health, which undercut charges of mere ideological motivation. It also encourages funders to regularly publish opportunities that will shape investigators’ areas of inquiry to those most important to racialized groups (for a recent example, see the US NIH's funding announcement, RFA-NS-22-002).
      Further, it is possible that biomarker discovery and analgesics developed while ignoring the influence of social indicators might not be valid for individuals who are systematically oppressed by such factors, ultimately running a high risk of racialized patients being further denied adequate pain treatment. Although current calls for pain biomarker discovery and validation advocate for the inclusion of participants from diverse populations,
      • Davis KD
      • Aghaeepour N
      • Ahn AH
      • Angst MS
      • Borsook D
      • Brenton A
      • Burczynski ME
      • Crean C
      • Edwards R
      • Gaudilliere B
      • Hergenroeder GW
      • Iadarola MJ
      • Iyengar S
      • Jiang Y
      • Kong J-T
      • Mackey S
      • Saab CY
      • Sang CN
      • Scholz J
      • Segerdahl M
      • Tracey I
      • Veasley C
      • Wang J
      • Wager TD
      • Wasan AD
      • Pelleymounter MA
      Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities.
      these recommendations do not include endpoints or measures that reflect patients’ diverse identities or provide guidance on how to incorporate social indicators into biomarker development. Researchers conducting translational work aimed at developing biomarkers or analgesics are strongly encouraged to consider social indicators and their psychological consequences in study design choices, moving toward a true biopsychosocial metanarrative. For example, sociocultural pain neuroscience has emerged as a subfield that addresses how sociocultural factors (including racism) intersect with individuals’ values/beliefs and modulate pain neurobiology to yield diverse pain experiences.
      • Anderson SR
      • Losin EAR
      A sociocultural neuroscience approach to pain.
      Concerted efforts, such as work in this subfield to integrate diverse psychosocial factors in biomedical pain research, will help us understand how to best intervene on pain inequities.

      Study Design Factor 2: Study Samples Often Have Low Numbers of Participants From Racialized Groups

      The inclusion of racialized groups in pain research is imperative for generalizability beyond NHW individuals. However, these groups have been largely underrepresented in most pain research produced from WEIRD countries. Efforts to encourage more inclusive research in these countries have consequently been implemented. For example, the US NIH Revitalization Act of 1993 was introduced to promote the inclusion of racialized groups in clinical research,

      grants.nih.gov: NIH policy and guidelines on the inclusion of women and minorities as subjects in clinical research., 2001. Available at: https://grants.nih.gov/policy/inclusion/women-andminorities/guidelines.htm#:∼:text=TheNIHRevitalizationActof,andminoritiesinclinicalresearch.&text=Thestatuteincludesaspecific,and%2Cinparticularclinicaltrials. Accessed March 1, 2021.

      and the “Outreach Notebook for the Inclusion, Recruitment, and Retention of Women and Minority Subjects in Clinical Research” is a complementary document designed to help investigators diversify study samples.
      Research NI of H (US). O of E, Committee NIHON
      Committee NIHT: Outreach Notebook for the Inclusion, Recruitment and Retention of Women and Minority Subjects in Clinical Research: Principal Investigators’ Notebook.
      The Revitalization Act requires NIH-funded investigators in the US to report enrolled participants’ sociodemographic characteristics annually. The NIH Research, Condition, and Disease Categories (RCDC) Inclusion Statistics Report (https://report.nih.gov/risr/#/) makes this information across NIH-funded studies publicly available.
      Table 3 lists the median proportions of participants’ identities, based on the US Office of Management and Budget's (OMB) “race” and ethnicity categories, across NIH-funded studies and within pain-related RCDCs during 2018. These data highlight that White and “non-Hispanic/Latino” (language used by OMB) individuals are overwhelmingly represented in US pain-related clinical research. Although the representation of racialized groups in pain-related RCDCs is similar to estimates from the 2010 US Census, the fact that pain inequities persist raises concerns about using Census estimates as an inclusion goal; it guarantees that there will be low generalizability beyond group(s) with the highest Census estimates. Although some degree of diversity is achieved by matching enrollment targets to US Census estimates (ie, who is in the room), this strategy ultimately limits inclusion (ie, whose voice is heard). Further, the US population is projected to change substantially from 2016 to 2060 (eg, an anticipated 101% increase in Asian individuals, 41% increase in Black/African American individuals, and 93.5% increase in Hispanic/Latino/a/e/x individuals).
      • Vespa J
      • Armstrong DM
      • Medina L
      Demographic Turning Points for the United States: Population Projections for 2020 to 2060.
      These projected changes emphasize the need for our field to set new enrollment standards and reframe study designs to proactively address the pain care needs of a diversifying society. Although these examples draw on US estimates, the considerations presented apply to investigators across WEIRD countries.
      Multiple study design choices can act as barriers to recruiting racialized individuals in research
      • Bonevski B
      • Randell M
      • Paul C
      • Chapman K
      • Twyman L
      • Bryant J
      • Brozek I
      • Hughes C
      Reaching the hard-to-reach: A systematic review of strategies for improving health and medical research with socially disadvantaged groups.
      (Fig 1). First, the selection of a study question with poor relevance to racialized individuals can influence initial interest in participation.
      • Corbie-Smith GM
      Minority recruitment and participation in health research.
      ,
      • Ejiogu N
      • Norbeck JH
      • Mason MA
      • Cromwell BC
      • Zonderman AB
      • Evans MK
      Recruitment and retention strategies for minority or poor clinical research participants: Lessons from the healthy aging in neighborhoods of diversity across the life span study.
      Second, strict inclusion/exclusion criteria around health factors particularly impacted by systemic racism (eg, BMI, diabetes
      • Bailey ZD
      • Krieger N
      • Agénor M
      • Graves J
      • Linos N
      • Bassett MT
      Structural racism and health inequities in the USA: Evidence and interventions.
      ,
      • Lukachko A
      • Hatzenbuehler ML
      • Keyes KM
      Structural racism and myocardial infarction in the United States.
      ,
      • Paradies Y
      • Ben J
      • Denson N
      • Elias A
      • Priest N
      • Pieterse A
      • Gupta A
      • Kelaher M
      • Gee G
      Racism as a determinant of health: A systematic review and meta-analysis.
      ) risk the systematic exclusion of individuals who are the targets of racism.
      • Ford JG
      • Howerton MW
      • Lai GY
      • Gary TL
      • Bolen S
      • Gibbons MC
      • Tilburt J
      • Baffi C
      • Tanpitukpongse TP
      • Wilson RF
      • Powe NR
      • Bass EB
      Barriers to recruiting underrepresented populations to cancer clinical trials: A systematic review.
      ,
      • Frierson GM
      • Williams DM
      • Dunsiger S
      • Lewis BA
      • Whiteley JA
      • Albrecht AE
      • Jakicic JM
      • Horowitz SM
      • Marcus BH
      Recruitment of a racially and ethnically diverse sample into a physical activity efficacy trial.
      Third, investigators’ choices of study procedures might inadvertently deter participation among individuals experiencing economic disenfranchisement if participation logistics present a high burden, such as the need to attend multiple in-person visits during work hours or arrange transportation.
      • Ejiogu N
      • Norbeck JH
      • Mason MA
      • Cromwell BC
      • Zonderman AB
      • Evans MK
      Recruitment and retention strategies for minority or poor clinical research participants: Lessons from the healthy aging in neighborhoods of diversity across the life span study.
      ,
      • Ford JG
      • Howerton MW
      • Lai GY
      • Gary TL
      • Bolen S
      • Gibbons MC
      • Tilburt J
      • Baffi C
      • Tanpitukpongse TP
      • Wilson RF
      • Powe NR
      • Bass EB
      Barriers to recruiting underrepresented populations to cancer clinical trials: A systematic review.
      Fourth, study materials designed without considering potential participants’ language fluency, literacy levels, and cultural diversity can further restrict racialized individuals’ participation, particularly for immigrants.
      • George S
      • Duran N
      • Norris K
      A systematic review of barriers and facilitators to minority research participation among African Americans, Latinos, Asian Americans, and Pacific Islanders.
      ,
      • Occa A
      • Morgan SE
      • Potter JE
      Underrepresentation of hispanics and other minorities in Clinical trials: Recruiters’ perspectives.
      Fifth, racialized community members might not be aware of research participation opportunities if recruitment materials are inadequately disseminated.
      • Ceballos RM
      • Knerr S
      • Scott MA
      • Hohl SD
      • Malen RC
      • Vilchis H
      • Thompson B
      Latino beliefs about biomedical research participation: A qualitative study on the U.S.-Mexico border.
      ,
      • Ford JG
      • Howerton MW
      • Lai GY
      • Gary TL
      • Bolen S
      • Gibbons MC
      • Tilburt J
      • Baffi C
      • Tanpitukpongse TP
      • Wilson RF
      • Powe NR
      • Bass EB
      Barriers to recruiting underrepresented populations to cancer clinical trials: A systematic review.
      Finally, the mistreatment of racialized individuals in science and healthcare settings undermines the trustworthiness of research establishments. Trust that is lost must be earned again through the investigative team's actions.
      • Guadagnolo BA
      • Cina K
      • Helbig P
      • Molloy K
      • Reiner M
      • Cook EF
      • Petereit DG
      Medical mistrust and less satisfaction with health care among Native Americans presenting for cancer treatment.
      ,
      • Schmotzer GL
      Barriers and facilitators to participation of minorities in clinical trials.
      Figure 1
      Figure 1Study design choices that act as barriers to diversity and inclusion in research study samples.
      The latter is particularly relevant for translational pain research, or research focused on taking discoveries of biological phenomena “from the bench to the bedside and back again”
      • Fort DG
      • Herr TM
      • Shaw PL
      • Gutzman KE
      • Starren JB
      Mapping the evolving definitions of translational research.
      (see Davis et al,
      • Davis KD
      • Aghaeepour N
      • Ahn AH
      • Angst MS
      • Borsook D
      • Brenton A
      • Burczynski ME
      • Crean C
      • Edwards R
      • Gaudilliere B
      • Hergenroeder GW
      • Iadarola MJ
      • Iyengar S
      • Jiang Y
      • Kong J-T
      • Mackey S
      • Saab CY
      • Sang CN
      • Scholz J
      • Segerdahl M
      • Tracey I
      • Veasley C
      • Wang J
      • Wager TD
      • Wasan AD
      • Pelleymounter MA
      Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities.
      Kraus,
      • Kraus VB
      Biomarkers as drug development tools: Discovery, validation, qualification and use.
      and Zarbin
      • Zarbin M
      What constitutes translational research? Implications for the scope of translational vision science and technology.
      for additional information). Translational research is considered a critical iterative process for biomarker discovery and validation as well as analgesic development and often features large-scale surveillance of physiological processes to identify potential intervention targets via biological fluids, tissues, or bioimages.
      • Kraus VB
      Biomarkers as drug development tools: Discovery, validation, qualification and use.
      This iterative process occurs on a spectrum of research activities that are conducted in phases from biomarker discovery and assay development (T0/T1) to the assessment of the benefit and uptake of analgesics or other therapeutic interventions at the population level.
      • Zarbin M
      What constitutes translational research? Implications for the scope of translational vision science and technology.
      For this reason, racialized groups that have historically experienced exploitation of their biological samples by researchers (discussed in Morais et al
      • Morais C
      • Aroke EN
      • Letzen JE
      • Campbell CM
      • Hood AM
      • Janevic MR
      • Mathur VA
      • Merriwether EN
      • Goodin BR
      • Booker SQ
      • Campbell LC
      Confronting Racism in Pain Research: A Call to Action.
      ) are justified in their mistrust. Without concerted efforts from investigators to build trust, studies that employ the collection of biological samples are particularly at risk of low sample diversity.
      Notably, the barriers described in Figure 1 are not always present from a lack of awareness or attention but might be present because of a lack of resources. As discussed by Hood et al,
      • Hood AM
      • Booker SQ
      • Morais CA
      • Goodin BR
      • Letzen JE
      • Campbell LC
      • Merriwether EN
      • Aroke EN
      • Campbell CM
      • Mathur VA
      • Janevic MR
      Confronting racism in pain research: A shared commitment for engagement, diversity, and dissemination.
      racialized investigators are often under-cited and under-resourced due to structures within academia/biomedical research. Yet, they are most likely to conduct community-engaged research. An antiracism framework would provide more funding opportunities for community-engaged research and would encourage collaborations between investigators from larger institutions with (in the US) investigators from Historically Black Colleges and Universities, Hispanic-Serving Institutions, Tribal Colleges and Universities, and Asian American and Pacific Islander Serving Institutions in a shared principal investigator role. Further, an antiracism framework calls on investigators from WEIRD societies to collaborate with and value the perspectives of investigators from the Global South who can offer alternatives to Eurocentric perspectives. This effort would be facilitated by increased resources and funding opportunities to support cross-cultural collaborations (eg, International Association for the Study of Pain Collaborative Research Grants).

      Antiracism Reframe 2: Adopt New Ideologies and Strategies to Promote Inclusion in Pain Research

      For new data collection, investigators can prioritize partnering with stakeholders from racialized groups to inform the research question, methods, and dissemination approach. Social location is a concept associated with Critical Race Theory (see Morais et al
      • Morais C
      • Aroke EN
      • Letzen JE
      • Campbell CM
      • Hood AM
      • Janevic MR
      • Mathur VA
      • Merriwether EN
      • Goodin BR
      • Booker SQ
      • Campbell LC
      Confronting Racism in Pain Research: A Call to Action.
      for background) that refers to an individual's or group's position in a social hierarchy based on dimensions of privilege and marginalization.
      • Ford CL
      • CO Airhihenbuwa
      The public health critical race methodology: Praxis for antiracism research.
      Metanarratives tend to be propagated by those with privileged social location; however, centering in the margins – or including the viewpoints of individuals with marginalized social location – can enrich metanarratives by balancing perspectives. The result is a research study grounded in scientific theory and evidence that is enriched by valuable perspectives from individuals’ lived experiences.
      • Thomas SB
      • Quinn SC
      • Butler J
      • Fryer CS
      • Garza MA
      Toward a fourth generation of disparities research to achieve health equity.
      We encourage all researchers committed to pain equity to partner with diverse community members to refine their research questions. Shifting to community-engaged research in the field of pain will have a universal benefit for the impact of our collective work. Strategies for partnering with stakeholders from racialized groups are described in Janevic et al
      • Janevic M
      • Mathur V
      • Booker S
      • Morais C
      • Meints S
      • Yeager K
      • Meghani S
      Making pain research more inclusive: Why and How.
      and Hood et al.
      • Hood AM
      • Booker SQ
      • Morais CA
      • Goodin BR
      • Letzen JE
      • Campbell LC
      • Merriwether EN
      • Aroke EN
      • Campbell CM
      • Mathur VA
      • Janevic MR
      Confronting racism in pain research: A shared commitment for engagement, diversity, and dissemination.
      For new or ongoing data collection, investigators can track the recruitment of individuals from racialized groups from the initial phone screen through the end of their participation in the research protocol, as well as collect qualitative data on individuals’ experiences participating in the study. These data can determine the effectiveness of strategies in reaching racialized communities, identify where screening criteria might systematically exclude certain racialized groups, and uncover reasons for individuals’ attrition. This information is often collected as part of the CONSORT approach
      • Boutron I
      • Altman DG
      • Moher D
      • Schulz KF
      • Ravaud P
      CONSORT statement for randomized trials of nonpharmacologic treatments: A 2017 update and a CONSORT extension for nonpharmacologic trial abstracts.
      for reporting recruitment and retention in randomized controlled trials and could be advanced through an antiracism framework by tracking this information across all human participants research and detailing where bias arises. Publishing these data alongside primary outcomes will be valuable information for investigators planning future studies on a similar topic.
      Further, the intended use of biospecimen/images, study objectives, risks, and benefits of participation for all clinical trials should be explicitly stated and translated for participants who are not fluent in the language used to communicate study information.
      • Umscheid CA
      • Margolis DJ
      • Grossman CE
      Key concepts of clinical trials: A narrative review.
      Transparency around biospecimen data collection and usage could be critically important for building and maintaining trust in the biomedical research process/investigators as well as reducing attrition among racialized groups that are already underrepresented and historically mistreated in biomedical research.
      For completed data collection, it is strongly recommended that pain researchers report the study's composition of racialized groups in all associated publications. If the study aimed to produce results that are generalizable across a diverse sample, yet mainly enrolled NHW participants, an antiracism framework encourages researchers to 1) note that a key limitation is the study's risk of perpetuating pain inequities and 2) provide a reflective statement for how the team will incorporate greater diversity/inclusion in future projects. Further, given that studies conducted with a sample of participants with racialized identities are often expected by peer reviewers to report the sample's racialized group identity in the publication's title or abstract, studies conducted with a sample of NHW participants should do the same to model parity. Otherwise, this practice conveys that a study with NHW participants is the accepted “norm” and studies reporting on findings within racialized groups are a deviation.

      Study Design Factor 3: Using “Race” as a Statistical Variable

      Two prevailing notions on the design of pain studies are that 1) pain disparities are measured by comparing 1 or more racialized groups to a NHW group (primary independent variable), and 2) “race” should be controlled for in statistical models (statistical control). These notions run a conditional risk of producing research products that unintentionally harm racialized individuals without ample thought and discussion of what the outcomes of these tests might mean.

      “Race” as a Primary Independent Variable

      Studies using “race” as the primary independent variable are considered a traditional approach to pain disparities research. In WEIRD societies, traditional designs compare 1 or more racialized groups to a NHW group, which is treated as a reference or accepted norm. There are several strengths to this approach: 1) it encourages inclusivity of racialized groups, 2) it elucidates where pain inequities exist and new inequities emerge, and 3) it builds from a rich literature foundation to track progress toward pain care equity. However, investigators should consider several inherent risk factors when applying this model, particularly when examining pain mechanisms.
      First, although comparing groups is effective for highlighting where differences exist, it is less effective for explaining why and how they emerge. In a prevailing biomedical metanarrative, the implied reasoning is that group differences in pain are somehow innate.
      • Plaut VC
      Diversity science: Why and how difference makes a difference.
      Even when biopsychosocial factors are considered in tandem, another assumption is often that group differences result from behavioral choices without recognizing the constraints imposed by a history of systemic oppression.
      • Salter PS
      • Adams G
      • Perez MJ
      Racism in the structure of everyday worlds: A cultural-psychological perspective.
      An examination of why disparities in pain exist and how they persist necessitates awareness of a historical perspective
      • Feagin J
      • Bennefield Z
      Systemic racism and US health care.
      (see Morais et al
      • Morais C
      • Aroke EN
      • Letzen JE
      • Campbell CM
      • Hood AM
      • Janevic MR
      • Mathur VA
      • Merriwether EN
      • Goodin BR
      • Booker SQ
      • Campbell LC
      Confronting Racism in Pain Research: A Call to Action.
      ) as well as recognition of contemporary sociopolitical forces that maintain disparities in lived experience.
      Second, the use of “race” as a primary independent variable has been a long-standing epistemological debate in the fields of epidemiology, nursing, psychology, and sociology,
      • Glymour MM
      • Spiegelman D
      Evaluating public health interventions: 5. Causal inference in public health research-do sex, race, and biological factors cause health outcomes?.
      ,
      • Jones CP
      • LaVeist TA
      • Lillie-Blanton M
      Race” in the epidemiologic literature: An examination of the American Journal of Epidemiology, 1921-1990.
      ,
      • Moscou S
      The conceptualization and operationalization of race and ethnicity by health services researchers.
      among others. Our group is not the first to consider the limitations of using “race” in study designs and aims to bring the expert opinions of those scholars who have critically evaluated this approach to the field of pain. Some scholars in these fields have contested that using “race” as a primary independent variable frames research questions around its effects on outcome distributions
      • Kaufman JS
      • Cooper RS
      Commentary: Considerations for use of racial/ethnic classification in etiologic research.
      (eg, how does “race” impact pain mechanisms?). The scholars on this side of the debate have further noted that the logic that might stem from using “race” in certain statistical tests – particularly those with causal inference – is that this factor is a variable upon which to intervene.
      • Kaufman JS
      • Cooper RS
      Commentary: Considerations for use of racial/ethnic classification in etiologic research.
      They note that this logic is ordinarily not researchers’ intent, and it is instead treated as an immutable factor and/or proxy measure of other explanatory variables,
      • Chandran A
      • Knapp E
      • Liu T
      • Dean LT
      A new era: Improving use of sociodemographic constructs in the analysis of pediatric cohort study data.
      ,
      • Jackson JW
      • VanderWeele TJ
      Decomposition analysis to identify intervention targets for reducing disparities.
      such as experiences of discrimination, access to healthcare resources, or other social indicators. Consequently, some scholars have indicated that progress toward health equity would be facilitated by directly measuring the hypothesized explanatory variables among racialized participants.
      • Chandran A
      • Knapp E
      • Liu T
      • Dean LT
      A new era: Improving use of sociodemographic constructs in the analysis of pediatric cohort study data.
      ,
      • Jones CP
      Invited commentary: “Race,” racism, and the practice of epidemiology.
      Further, questions have been raised about how to best measure “race,”
      • Drevdahl DJ
      • Philips DA
      • Taylor JY
      Uncontested categories: The use of race and ethnicity variables in nursing research.
      and there has been debate on whether “race” should be considered as an immutable factor (ie, characteristic of the person) or a contextual factor in meaning/significance depending on the society in which the individual lives.
      • Jones CP
      Invited commentary: “Race,” racism, and the practice of epidemiology.
      Third, a NHW reference group in studies examining patterns of pain care can help identify areas in which racialized groups are inequitably treated. However, as emphasized by Booker et al
      • Booker SQ
      • Bartley EJ
      • Powell-Roach K
      • Palit S
      • Morais C
      • Thompson OJ
      • Cruz-Almeida Y
      • Fillingim RB
      The imperative for racial equality in pain science: A way forward.
      and Janevic et al,
      • Janevic M
      • Mathur V
      • Booker S
      • Morais C
      • Meints S
      • Yeager K
      • Meghani S
      Making pain research more inclusive: Why and How.
      the use of a NHW reference group can lead to study narratives that portray this group as the accepted “norm” and racialized groups as diverging from this norm (Table 2).
      Table 2Example Scenarios for How to Apply Antiracism Reframes for Common Study Design Factors
      Design factorExample scenarioCommon approachAntiracism approach
      Social Indicators of PainPrevious work has robustly documented sleep as a predictor of pain outcomes. An investigator would like to ask a research question to better understand the mechanisms of this association.Using a biomedical metanarrative, the investigator would ask, “What are the neural pathways and inflammatory mediators of this association?”Using a biopsychosocial metanarrative, the investigator would ask, “Do social factors create conditions by which sleep is unjustly distributed across the population? If so, are there unique psychophysiological pathways by which sleep and pain are associated for individuals who systematically experience sleep disturbance due to certain social factors?”
      Sample DiversityAfter several months of recruitment, an investigator is concerned about the enrollment of mostly NHW participants in their study sample.The investigator expresses a desire to have a diverse study sample. They explain, however, that racialized groups are “hard to reach” and “distrust” the medical system and continue with their current methods.The investigator reflects on ways that their recruitment practices inadvertently exclude certain groups on a systematic basis, include and value coinvestigators with expertise in community-engaged research, and/or partner with racialized community members to implement new recruitment practices.
      “Race” as a Statistical VariableIn seeking to understand children's pain coping styles, an investigator administers questionnaires to NHW and Black school-aged children on pain coping and quality of life.The investigator finds that NHW children are enrolled in Cognitive-Behavioral Therapy at a higher rate than their Black peers, who tend to cope through prayer and community support. They interpret results as greater use of “active” coping strategies among NHW children and greater use of “passive” coping among Black children.The investigator first conducts a qualitative study with Black children/families to identify themes around pain coping. They use this information in a larger follow-up study to quantitatively examine how these themes associate with children's use of coping strategies and quality of life. They do not label coping styles based on NHW American cultural values in their discussion of results.
      Translation of Preclinical Science to Diverse HumansAn investigator seeks to use a mouse model to examine and validate a therapeutic target for an analgesicThe investigator examines this therapeutic target for an analgesic across a strain of mice that have developed under the same living conditions.The investigator appreciates that systemic racism causes unique developmental conditions and aims to model these conditions so that not all mice in their sample are raised equitably. They then examine whether the therapeutic target and analgesic has unique mechanisms of action or efficacy based on these disparate conditions.
      Abbreviation: NHW, Non-Hispanic White.
      Table 3“Race” and Ethnicity Category Data in Pain-Related Topics From the Publicly Available National Institutes of Health Research, Condition, and Disease Categories Inclusion Statistics Report
      Median % across study samples
      US Office of Management and Budget Categories
      Specific category names (eg, “Hispanic, Latino,” “Other Pacific Islander”) are shown as they appear in the online RCDC tables and do not reflect the ACTION-PR's choices.
      RCDCTotal participants across studiesAmerican Indian, Alaska nativeAsianNative Hawaiian, OPIBlack, African American>1 “Race”WhiteUK, URHispanic, LatinoNot Hispanic, LatinoUK, UR
      Arthritis36,146<1%<1%<1%7%<1%72%<1%2%93%<1%
      Back Pain1,518<1%5%<1%16%<1%63%2%8%88%<1%
      Chronic Pain147,997<1%1%<1%11%<1%72%<1%5%93%<1%
      Fibromyalgia1,500<1%<1%<1%5%<1%89%3%3%94%<1%
      Headaches1,659<1%6%<1%7%3%80%1%6%90%<1%
      Migraines1,182<1%9%<1%6%3%77%2%6%90%<1%
      Neck Pain307%7%3%10%<1%73%<1%13%87%<1%
      Neurosciences1,217,529<1%2%<1%8%<1%70%<1%5%92%<1%
      Opioid Misuse and Addiction26,421<1%<1%<1%13%1%67%<1%4%94%<1%
      Osteoarthritis25,837<1%<1%<1%11%<1%74%<1%1%98%<1%
      Pain Research180,452<1%<1%<1%11%<1%71%<1%4%94%<1%
      Rheumatoid Arthritis9,529<1%2%<1%7%<1%69%6%7%85%<1%
      TMJD1,147<1%5%<1%5%5%82%<1%7%91%<1%
      Abbreviations: RCDC, Research, Condition, and Disease Categories; OPI, Other Pacific Islander; UK, UR, Unknown, Unreported; TMJD, Temporomandibular Muscle/Joint Disorder.
      low asterisk Specific category names (eg, “Hispanic, Latino,” “Other Pacific Islander”) are shown as they appear in the online RCDC tables and do not reflect the ACTION-PR's choices.
      Fourth, dichotomizing groups restricts the examination of within-group heterogeneity
      • Levine DS
      • Taylor RJ
      • Nguyen AW
      • Chatters LM
      • Himle JA
      Family and friendship informal support networks and social anxiety disorder among African Americans and Black Caribbeans.
      (also see Booker et al,
      • Booker SQ
      • Bartley EJ
      • Powell-Roach K
      • Palit S
      • Morais C
      • Thompson OJ
      • Cruz-Almeida Y
      • Fillingim RB
      The imperative for racial equality in pain science: A way forward.
      Janevic et al
      • Janevic M
      • Mathur V
      • Booker S
      • Morais C
      • Meints S
      • Yeager K
      • Meghani S
      Making pain research more inclusive: Why and How.
      ). Research in the US often uses panethnic categories specified by the OMB, rather than allowing individuals to self-report their identity. Although there are some shared experiences among individuals with the same panethnic identity, there is also substantial heterogeneity that is missed when collapsing across subidentities.
      • Griffith DM
      • Johnson JL
      • Zhang R
      • Neighbors HW
      • Jackson JS
      Ethnicity, nativity, and the health of American Blacks.
      For example, disaggregating panethnic categories shows unique patterns of disease morbidity and mortality based on factors such as country of origin and age of immigration to the US.
      • Fenelon A
      • Chinn JJ
      • Anderson RN
      A comprehensive analysis of the mortality experience of hispanic subgroups in the United States: Variation by age, country of origin, and nativity.
      ,
      • Fuller-Thomson E
      • Brennenstuhl S
      • Hurd M
      Comparison of disability rates among older adults in aggregated and separate Asian American/Pacific Islander Subpopulations.
      ,
      • Hamilton TG
      • Hummer RA
      Immigration and the health of U.S. black adults: Does country of origin matter?.
      ,
      • Read JG
      • Lynch SM
      • West JS
      Disaggregating heterogeneity among non-Hispanic whites: Evidence and implications for U.S. racial/ethnic health disparities.

      “Race” as a Statistical Control

      Another common use for “race” in statistical models is to apply this factor as a control variable to examine associations between another primary variable and the outcome of interest.
      • Janevic M
      • Mathur V
      • Booker S
      • Morais C
      • Meints S
      • Yeager K
      • Meghani S
      Making pain research more inclusive: Why and How.
      Scholars opine that “race” is a complex and ambiguous sociopolitical concept that lacks specificity.
      • Kaplan JB
      • Bennett T
      Use of race and ethnicity in biomedical publication.
      ,
      • Phinney JS
      When we talk about American ethnic groups, what do we mean?.
      Because investigators rarely justify which definition of “race” is used for deriving this variable, it is often unclear why the statistical adjustment is being made.
      • LaVeist TA
      Beyond dummy variables and sample selection: What health services researchers ought to know about race as a variable.
      In other words, adjusting for “race” provides little insight into the role or meaning of this factor in the model and can lead to inappropriate conclusions.
      • Karran EL
      • Grant AR
      • Moseley GL
      Low back pain and the social determinants of health: A systematic review and narrative synthesis.
      Another disadvantage cited is that conceptualizing “race” as a confounder in the association between a factor and health outcome treats it as something to be discarded or discounted rather than explored to understand why this factor should be adjusted for in the first place.
      • Jones CP
      Invited commentary: “Race,” racism, and the practice of epidemiology.
      Although adjusting for “race” is thought to be less problematic than using it as the primary independent variable, scholars note that specific explanatory variables may reduce bias in models more effectively than using “race” as a proxy for those factors.
      • Kaufman JS
      • Cooper RS
      Commentary: Considerations for use of racial/ethnic classification in etiologic research.

      Antiracism Reframe 3: Measure Lived Experiences Pertinent to Racialized Individuals and Interpret Findings in this Context

      Although there are limitations for the use of a traditional pain disparities design or statistically controlling for “race,” research questions should always dictate study designs. For research seeking to examine inequities in pain referrals, assessment, and treatment, a traditional pain disparities design is imperative to track progress toward equitable pain care. The NHW group serves as a reference in this case because WEIRD societies are unjustly structured to benefit NHW individuals. Therefore, comparing racialized groups to a NHW reference group in a clinical context can highlight bias in pain care.
      To adopt an antiracism reframe, investigators using a traditional disparities design can 1) discuss the rationale for using a NHW reference group, 2) measure and discuss proximal mediators contributing to inequities, and 3) hold oppressive systems accountable where inequities are identified. Studies statistically adjusting for “race” can be intentional about using this variable by explaining how it is expected to associate with the study's primary variables and whether it is serving as a proxy for other unmeasured variables.
      • LaVeist TA
      Beyond dummy variables and sample selection: What health services researchers ought to know about race as a variable.
      A traditional pain disparities design runs a conditionally higher risk of harming racialized groups when examining pain mechanisms. This is not to say that all mechanistic work using a traditional disparities approach has been or will be harmful; in fact, much valuable work has been done to disprove myths about lower pain sensitivity that were used to justify the enslavement of Black individuals in the US.
      • Guillory JD
      The pro-slavery arguments of Dr. Samuel A. Cartwright.
      Traditional pain disparities designs have also helped highlight where group differences might warrant further exploration. However, an antiracism framework advocates for 1) extra care and self-reflection on biases in interpreting why groups are being compared in the first place and what observed differences might mean and 2) framing research questions around root causes of racialized disparities rather than simply continuing to document where disparities exist.
      In an influential paper, Plaut (2010)
      • Plaut VC
      Diversity science: Why and how difference makes a difference.
      defines diversity science as the study of the dynamic process by which observed group differences are constructed, interpreted, and rerepresented across structures, institutions, and cultural understanding. Applying an antiracism, diversity science approach to pain would include a shift from assumptions based on group averages toward an interest in variability. To create this shift, pain researchers can consider the diversity of identities, lived experiences, contexts, and histories that differentially influence pain. In the supplementary materials, Table S1 provides numerous examples of lived experiences that can be examined in pain research to help us move beyond a NHW lens (eg, familism, racism-related stress, discrimination, measures of structural racism). We do not intend for every researcher to include measures of all examples listed in the table in their studies; choosing explanatory factors to include in a study is best done with input from stakeholders from racialized groups. However, we provide an extensive list of potential explanatory variables that, to date, have seldom been considered in pain research.
      This process would be further facilitated by underused research approaches in this area, including qualitative/mixed methods and statistical models that account for racism at multiple levels. Qualitative and mixed-methods approaches align with an antiracism framework when centering the voices of racialized individuals living with pain. However, a study does not need to include qualitative or mixed-methods to be conducted in the spirit of antiracism. Further, preclinical and clinical researchers who acknowledge the lens through which they view their work – a practice often used in qualitative/mixed-methods studies – can help readers understand factors that shaped the authors’ interpretation of their work. Another area of growth is for the field to examine how racism at micro-, meso-, and macro-levels impacts pain experiences, which will help identify areas where intervention might be most critical (see Sewell for additional explanation on multilevel statistical models to understand the impact of racism on racialized health disparities
      • Sewell AA
      ). Additional methods to expand beyond a traditional disparities approach are discussed by Stewart and Sewell.

      Sewell AA, Stewart QT: Quantifying race: On methods for analyzing social inequality, Rethinking Race and Ethnicity in Research Methods, Stanfield JH, II, Routledge; New York, 2021, pp 209–234

      In these updated approaches, the location of the “problem” or “vulnerability” shifts away from an individual (ie, biology and individual choice) to upstream causes at the level of society and structures. Instead of asking, “how does ‘race’ associate with pain outcomes?” an antiracism reframe asks, “how does racism (or other lived experience) associate with pain outcomes among racialized individuals?”
      • Crear-Perry J
      • Maybank A
      • Keeys M
      • Mitchell N
      • Godbolt D
      Moving towards anti-racist praxis in medicine.
      Thirty years ago, David and colleagues
      • David RJ
      • Collins JWJ
      Bad outcomes in black babies: Race or racism?.
      understood this difference and called for a shift in focus from “race” to racism to improve perinatal outcomes, which was ultimately not sufficiently answered by the field. Substantial time and resources have since been invested to continue documenting dangerously high preterm birth and infant mortality rates for Black newborns that have persisted since the Jim Crow era
      • Driscoll AK
      • Ely DM
      Effects of changes in maternal age distribution and maternal age-specific infant mortality rates on infant mortality trends: United States, 2000-2017.
      ; however, limited progress has been made in moving beyond group comparisons to address the mechanisms that perpetuate racialized disparities.
      To illustrate this shift in study design related to pain, we reanalyzed our (Letzen, CM Campbell) published data reporting differences between healthy Black and NHW adults in μ-opioid receptor binding potential during the experience of noxious stimuli.
      • Letzen JE
      • Mun CJ
      • Kuwabara H
      • Burton EF
      • Boring BL
      • Walls T
      • Speed TJ
      • Wong DF
      • Campbell CM
      Ethnic disparities in pain processing among healthy adults: Mu-opioid receptor binding potential as a putative mechanism.
      Although this project was one of the first to examine physiological pathways of heightened pain sensitivity (on average) among Black adults, it could not identify why differences emerged (ie, “the causes of the causes”) Fig 2A shows part of the original group comparison on mean μ-opioid receptor binding potential values in the ventral striatum, a region associated with discrimination in the context of racialized pain disparities.
      • Losin EAR
      • Woo C-W
      • Medina NA
      • Andrews-Hanna JR
      • Eisenbarth H
      • Wager TD
      Neural and sociocultural mediators of ethnic differences in pain.
      On average, binding potential in the bilateral ventral striatum was greater among Black adults. Using an antiracism reframe in the present article, we reanalyzed these data to examine the association between μ-opioid receptor binding potential and severity of experienced ethnic discrimination and social exclusion (Fig 2B). In reflecting on how we wanted to approach this reanalysis, we chose to examine data across the sample, rather than use participants’ reported “race” as a moderator; however, this is just 1 way that an antiracism reframe could have been applied to these data. We found significant, positive associations between binding potential values with experienced ethnic discrimination (r = .30, P = .04) and social exclusion (r = .32, P = .02). This antiracism reframe highlights that discrimination/social exclusion is associated with pain-related neurophysiology, considers a lived experience that is particularly salient to Black individuals living in a racist society, elucidates a mechanism from social experience to physiology, and identifies discrimination/social exclusion as potential intervention targets to reduce the disparate burden on pain-related neurophysiology.
      Figure 2
      Figure 2Example of an antiracism reframe from a traditional pain disparities framework (A) to a measure of lived experience (B).
      Our suggestion to incorporate this particular reframe in the field of pain is not a recommendation to abolish the exploration of racialized differences in pain. Assuming parity between NHW and racialized groups where disparities exist risks maintaining pain inequities. Instead, it emphasizes the importance of self-reflection, cultural humility, and consultation with stakeholders in deciding whether to compare groups, intentionality in the use of “race” as a statistical variable, and consideration of lived experiences that will enhance interpretation of findings from a social contextual perspective as well as lead to more effective and relevant pain interventions for racialized groups. Further, given measurement issues with the construct of “race” (see Ross et al,
      • Ross PT
      • Hart-Johnson T
      • Santen SA
      • Zaidi NLB
      Considerations for using race and ethnicity as quantitative variables in medical education research.
      for recommendations on how to measure and report identity in health research), measuring lived experiences has the potential to lead to more tangible solutions to address health inequities.
      By considering social indicators or developing pain treatments that include the needs of racialized groups, we do not advocate for race-based medicine that relies on a patient's skin tone to make clinical decisions. Rather, we advocate for an improved understanding of the embodiment of systemic oppression on pain physiology and the recognition of multicultural pain expressions. There is an ethical and professional need to develop pain treatments that lead to pain care equity.
      • Narayan MC
      Culture’s effects on pain assessment and management.
      ,

      Perry M, Shahidullah JD, Lynch MK: Moving towards cultural competence in the treatment of pediatric chronic pain, 2019.

      ,
      • Robinson-Lane SG
      • Booker SQ
      Culturally responsive pain management for black older adults.
      The development of analgesics and nonpharmacological therapies within contexts that consider, and are not blind too, the reality of racialized differences in lived experiences will likely accelerate progress toward equity.

      Study Design Factor 4: Preclinical Studies Rarely Model the Effects of Social Factors on Pain Physiology

      The T0/T1 phases of translational research are critical to the development of novel analgesic therapies because of their focus on biomarker discovery, assay development, and rigorous validation of targets in preclinical (animal) models and humans.
      • Davis KD
      • Aghaeepour N
      • Ahn AH
      • Angst MS
      • Borsook D
      • Brenton A
      • Burczynski ME
      • Crean C
      • Edwards R
      • Gaudilliere B
      • Hergenroeder GW
      • Iadarola MJ
      • Iyengar S
      • Jiang Y
      • Kong J-T
      • Mackey S
      • Saab CY
      • Sang CN
      • Scholz J
      • Segerdahl M
      • Tracey I
      • Veasley C
      • Wang J
      • Wager TD
      • Wasan AD
      • Pelleymounter MA
      Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities.
      ,
      • Kraus VB
      Biomarkers as drug development tools: Discovery, validation, qualification and use.
      Although preclinical models rarely focus on how social indicators contribute to pain and analgesia, they offer opportunities to investigate the impact of these indicators on specific cellular and molecular mechanisms with a level of precision that cannot be achieved in human studies.
      • Harnett NG
      Neurobiological consequences of racial disparities and environmental risks: A critical gap in understanding psychiatric disorders.
      In our review of preclinical pain studies, we found few that focused on social mechanisms and were not able to find any studies that have modeled the effects of racism-related stress on pain physiology.
      Racism-related stress is multidimensional and differs from other forms of stress. It includes: 1) racism-related life events (ie, salient racist acts that an individual has experienced), 2) racism microaggressions (ie, insidious racist acts that occur on a more frequent basis), 3) vicarious racism (ie, the observation of racist events impacting members of one's racialized group; eg, a Black child observing police brutality against a Black adult), 4) collective experiences of racism (ie, knowledge of racist events that happened to members of one's racialized group; eg, Japanese internment camps in the US), 5) intergenerational trauma (ie, emotional and behavioral responses to a traumatic event among the descendants of an individual who experienced the event), 6) social role demands and the need to adapt to White or dominant group society, and 7) structural/institutional racism's impact on living conditions, access to resources, and opportunities.
      • Harrell SP
      A multidimensional conceptualization of racism-related stress: Implications for the well-being of people of color.
      Finally, unlike some other forms of stress, the impact of racism-related stress occurs across the lifespan.
      The paucity of research on preclinical modeling of racism-related stress and other social indicators indicates that it will be important to develop best practices for preclinical studies using an antiracism framework, if these studies are to be used as predictive models of diverse human pain experiences. As noted in Morais et al,
      • Morais C
      • Aroke EN
      • Letzen JE
      • Campbell CM
      • Hood AM
      • Janevic MR
      • Mathur VA
      • Merriwether EN
      • Goodin BR
      • Booker SQ
      • Campbell LC
      Confronting Racism in Pain Research: A Call to Action.
      a limitation of the ACTION-PR is that our group includes mostly clinical researchers and the perspectives of 1 translational science researcher (E.M.) and 1 preclinical science researcher (M.B.). Understanding this limitation, we highly encourage preclinical researchers to similarly organize, gather, and brainstorm ways to best model experiences of racism-related stress and other social indicators that lead to inequitable pain experiences, and disseminate these recommendations to the pain field. Moreover, adopting these frameworks could foster earlier engagement with clinical, population health, and implementation science researchers at these critical phases of biomarker identification and therapeutic development. Although adopting new frameworks in established research practices can be challenging, it is not unattainable. As described in the introduction, advocacy for the consideration of sex as a biological variable, for example, has led to the inclusion of female animals in basic science and, in turn, improved the generalizability of findings.
      • Lee SK
      Sex as an important biological variable in biomedical research.

      Antiracism Reframe 4: Develop Translational Research Models for the Impact of Social Indicators on Physiological Pain Processes

      We encourage preclinical researchers to consider how to model constructs of racism-related stress – similar to how they have risen to the challenge of modeling other aspects of human behaviors, cognitive processes, and conditions – and other social indicators. With innovations in paradigm design and animal strain type, this information would help us understand how a systematically added burden of oppression across the lifespan impacts pain, nocifensive behaviors, and/or a candidate analgesic's mechanism of action. It could also more precisely identify neuronal, epigenetic, and cellular pathways that predict susceptibility or resilience to chronic pain across diverse humans. Effective modeling of racism-related stress, in particular, might require a combination of paradigms that manipulate interactions and environmental conditions across the lifespan. Below are examples of existing models that might act as analogues for isolated aspects of racism-related stress that can be combined to emulate the multidimensional impact of racism-related stress. We hope these examples will spark discussions among preclinical researchers and lead to the development of translational pain research using an antiracism framework (Fig 3).
      Figure 3
      Figure 3Integration of antiracism practices in translational research.
      As an analog to racism-related life events and racism microaggressions, interpersonal social stressors can be modeled. Examples of approaches to model such stressors include repeated social defeat stress, chronic social subordination stress, maternal separation, neonatal isolation, and manipulations in postweaning housing conditions.
      • Czéh B
      • Fuchs E
      • Wiborg O
      • Simon M
      Animal models of major depression and their clinical implications.
      ,
      • Golden SA
      • Covington HE
      • Berton O
      • Russo SJ
      A standardized protocol for repeated social defeat stress in mice.
      ,
      • Neisewander JL
      • Peartree NA
      • Pentkowski NS
      Emotional valence and context of social influences on drug abuse-related behavior in animal models of social stress and prosocial interaction.
      Further, given that certain racialized groups are over 3 times more likely to be in solitary confinement when incarcerated in the US
      • Sakoda RT
      • Simes JT
      Solitary confinement and the U.S. prison boom.
      (and are incarcerated at a systematically higher rate due to discriminatory policing), understanding pain responses among single-housed animals as an analog for solitary confinement could highlight pain mechanisms under unmet needs for social contact. Vicarious and intergenerational social stressors have been modeled using vicarious social defeat stress
      • Sial OK
      • Warren BL
      • Alcantara LF
      • Parise EM
      • Bolaños-Guzmán CA
      Vicarious social defeat stress: Bridging the gap between physical and emotional stress.
      and predator stress during pregnancy to examine epigenetics.
      • Bhattacharya S
      • Fontaine A
      • MacCallum PE
      • Drover J
      • Blundell J
      Stress across generations: DNA methylation as a potential mechanism underlying intergenerational effects of stress in both post-traumatic stress disorder and pre-clinical predator stress rodent models.
      ,
      • Blaze J
      • Roth TL
      Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation.
      Inequities in living conditions caused by structural racism can be modeled with manipulations such as fasting or nutrition deprivation, enriched versus deprived housing,
      • Amaro H
      • Sanchez M
      • Bautista T
      • Cox R
      Social vulnerabilities for substance use: Stressors, socially toxic environments, and discrimination and racism.
      and single versus multianimal housing.
      • Gage SH
      • Sumnall HR
      Rat park: How a rat paradise changed the narrative of addiction.
      Environmental toxins, another aspect of structural racism, can also be introduced at systematically different rates into the animals’ environments to determine their impact on pain physiology and analgesic responses.
      • Germolec D
      • Kono DH
      • Pfau JC
      • Pollard KM
      Animal models used to examine the role of the environment in the development of autoimmune disease: Findings from an NIEHS Expert Panel Workshop.
      Finally, resilience factors, such as social support, can be modeled using conspecific pairings prior to or during a manipulation.
      • Fritz M
      • El Rawas R
      • Salti A
      • Klement S
      • Bardo MT
      • Kemmler G
      • Dechant G
      • Saria A
      • Zernig G
      Reversal of cocaine-conditioned place preference and mesocorticolimbic Zif268 expression by social interaction in rats.
      Because racism-related stress is chronic, paradigms might be most impactful when conducted repeatedly rather than acutely. Where appropriate, they should also be administered across development (see Lupien et al
      • Lupien SJ
      • McEwen BS
      • Gunnar MR
      • Heim C
      Effects of stress throughout the lifespan on the brain, behaviour and cognition.
      for a review on animal models of stress from a lifespan perspective) and can be used to determine how changes in these factors over a lifespan influence pain pathways. For example, animal models can help us better understand how having adverse childhood experiences might increase chronic pain risk and/or prosocial support later in development can change the course of symptoms.
      Although racialized identity is a sociopolitical construct, an antiracism framework acknowledges that there is genetic variability across humans based on ancestry. Seeking to understand how pain mechanisms and candidate analgesics function while considering genetic variability will inform whether to anticipate select or widespread translation of findings and will have a universal benefit. A fundamental aspect of preclinical experimental design is to determine the animals’ inbred (similarity in responses) or outbred (genetic variability) strain type. Typically, C57 black background animals are considered the “gold standard” because of their inbred nature, low variability in behavioral output, and responses to various stimuli like alcohol and a high-fat diet. However, there is a debate that outbred animals have a variable genetic background that is more analogous to humans. Determining whether to use similar inbred animals versus more variable outbred animals has implications for the genetic diversity of translational research samples; it cannot and should not be used, however, to make conclusions about specific groups of people based on “race” or ethnicity.
      This reframe can be considered even after therapeutic targets and the uptake of analgesic therapies or other therapeutic interventions have been established. This allows for bidirectional approaches to the refinement of therapeutic targets, dosing, or mode of administration from the preclinical level to diverse humans at the population level. This approach could spawn much needed collaboration between diverse people with lived experience of pain and preclinical, clinical, and population health researchers.

      Conclusions

      The fundamental goal of pain research is to reduce the burden of pain and enhance individuals’ wellbeing. Although our field's intent is to apply this goal across individuals of diverse backgrounds, our study design choices can impact how well this goal is met. Shifting the field of pain toward antiracism research practices will work toward the elimination of long-standing inequities for racialized groups in pain care and create true strides toward equity. As discussed in Part 1 of this series (Morais et al
      • Morais C
      • Aroke EN
      • Letzen JE
      • Campbell CM
      • Hood AM
      • Janevic MR
      • Mathur VA
      • Merriwether EN
      • Goodin BR
      • Booker SQ
      • Campbell LC
      Confronting Racism in Pain Research: A Call to Action.
      ), investigators should strive to build cultural humility to engender self-awareness of the impact of their study design choices as a foundational step toward antiracism in pain research. Table 4 provides self-reflection questions to facilitate the latter process. As discussed in Part 3 of this series (Hood et al
      • Hood AM
      • Booker SQ
      • Morais CA
      • Goodin BR
      • Letzen JE
      • Campbell LC
      • Merriwether EN
      • Aroke EN
      • Campbell CM
      • Mathur VA
      • Janevic MR
      Confronting racism in pain research: A shared commitment for engagement, diversity, and dissemination.
      ), engaging with racialized communities as research partners, diversifying research environments, and expanding dissemination approaches will further progress the field toward this goal. Ongoing discussions about the effectiveness of these proposed antiracism reframes in attaining equity for racialized groups in pain care is encouraged.
      Table 4Reflection Questions for the Research Process to Encourage Antiracism in Pain Research Practices
      Design factorsInvestigator self-reflection questions
      Social Indicators of Pain•Does the study contribute to a biomedical metanarrative of pain more so than a biopsychosocial metanarrative?

      •Do societal inequities mediate or moderate the associations among the research question's biomedical or psychological variables?
      Sample Diversity•Does the research question consider the needs of racialized individuals living with pain?

      •Have diverse stakeholders been consulted in forming the research question, recruitment strategies, and dissemination of results?

      •Is there a collaborator with expertise in community-engaged research who can be included on the project? Will this collaborator be appropriately compensated?

      •Has the investigative team participated in training in antiracism, cultural humility, and multiculturalism?
      “Race” as a Statistical Variable•If “race” is hypothesized as a proxy measure for a set of lived experiences, is it possible to directly measure and test those experiences instead? Have the limitations of using “race” as a proxy for lived experiences been discussed in the scientific narrative?

      •Has “race” been described in the scientific narrative as a sociopolitical construct?

      •If comparing groups, what is the rationale for this comparison? Is 1 group treated as the reference/norm?

      •Has there been an attempt to ask about cultural/national identity within panethnic categories?
      Translation of Preclinical Basic Science to Diverse Humans•Do behavioral assays used in the study account for the diversity of lived experiences based on social indicators? Are social indicators used as explanatory variables?

      •Is biological data appropriately integrated or harmonized with measures of the lived experiences in human participants?

      •Do AI algorithms for prediction models and complex statistical analyses incorporate social indicators?

      •Is there genetic diversity among the animals being used in the study? If not, has the scientific narrative discussed how this factor might limit the findings’ generalization across genetic ancestries?

      Acknowledgments

      In the Fall of 2020, several of our pain disparities colleagues joined us for a virtual think tank about antiracism in pain research. We appreciate their time and valuable insights that shaped the approach to this series. The following individuals have provided written approval to acknowledge their individual role in the think tank: Emily Bartley, PhD; Amber Brooks, MD; Yenisel Cruz-Almeida, PhD; Troy Dildine; Roger Fillingim, PhD; Elizabeth Losin, PhD; Megan Miller, PhD; Chung Jung Mun, PhD; Andrea Newman, PhD; Michael “Alec” Owens, PhD; Fenan Rassu, PhD; Jamie Rhudy, PhD; Keesha Roach, PhD; Sheria Robinson-Lane, PhD, RN; Ellen Terry, PhD; Benjamin Van Dyke, PhD. Additionally, we would like to thank 4 researchers and 8 National Institutes of Health affiliates who will remain anonymous.

      Appendix. Supplementary data

      References

        • Adam EK
        • Heissel JA
        • Zeiders KH
        • Richeson JA
        • Ross EC
        • Ehrlich KB
        • Levy DJ
        • Kemeny M
        • Brodish AB
        • Malanchuk O
        • Peck SC
        • Fuller-Rowell TE
        • Eccles JS
        Developmental histories of perceived racial discrimination and diurnal cortisol profiles in adulthood: A 20-year prospective study.
        Psychoneuroendocrinology. 2015; 62 (Available at:) (Accessed March 1, 2021.): 279-291
        • Amaro H
        • Sanchez M
        • Bautista T
        • Cox R
        Social vulnerabilities for substance use: Stressors, socially toxic environments, and discrimination and racism.
        Neuropharmacology. 2021; 188 (Available at:) (Accessed March 1, 2021.)108518
        • Anderson SR
        • Losin EAR
        A sociocultural neuroscience approach to pain.
        Cult Brain. 2017; 5: 14-35
        • Bailey ZD
        • Krieger N
        • Agénor M
        • Graves J
        • Linos N
        • Bassett MT
        Structural racism and health inequities in the USA: Evidence and interventions.
        Lancet (London, England). 2017; 389: 1453-1463
        • Barcelona de Mendoza V
        • Huang Y
        • Crusto CA
        • Sun Y V
        • Taylor JY
        Perceived Racial Discrimination and DNA Methylation Among African American Women in the InterGEN Study.
        Biol Res Nurs. 2018; 20 (2017/12/19. SAGE Publications. Available at:) (Accessed March 1, 2021.): 145-152
        • Bell KA
        • Kobayashi I
        • Akeeb A
        • Lavela J
        • Mellman TA
        Emotional response to perceived racism and nocturnal heart rate variability in young adult African Americans.
        J Psychosom Res. 2019; 121 (England): 88-92
        • Berry-James RM
        • Gooden ST
        • Johnson III, RG
        Civil rights, social equity, and census 2020.
        Public Adm Rev. 2020; 80 (Wiley Online Library): 1100-1108
        • Bhattacharya S
        • Fontaine A
        • MacCallum PE
        • Drover J
        • Blundell J
        Stress across generations: DNA methylation as a potential mechanism underlying intergenerational effects of stress in both post-traumatic stress disorder and pre-clinical predator stress rodent models.
        Front Behav Neurosci. 2019; 13 (Frontiers Media S.A. Available at:) (Accessed March 1, 2021.): 113
        • Blaze J
        • Roth TL
        Evidence from clinical and animal model studies of the long-term and transgenerational impact of stress on DNA methylation.
        Semin Cell Dev Biol Elsevier. 2015; 43: 76-84
        • Blyth FM
        • Macfarlane GJ
        • Nicholas MK
        The contribution of psychosocial factors to the development of chronic pain: The key to better outcomes for patients?.
        Pain [Internet]. 2007; 129 (Available at:) (Accessed March 1, 2021.): 8-11
        • Bonevski B
        • Randell M
        • Paul C
        • Chapman K
        • Twyman L
        • Bryant J
        • Brozek I
        • Hughes C
        Reaching the hard-to-reach: A systematic review of strategies for improving health and medical research with socially disadvantaged groups.
        BMC Med Res Methodol [Internet]. 2014; 14: 42
        • Bonnett A
        The Americanisation of anti-racism? Global power and hegemony in ethnic equity.
        J Ethn Migr Stud. 2006; 32 (Taylor & Francis): 1083-1103
        • Booker SQ
        • Bartley EJ
        • Powell-Roach K
        • Palit S
        • Morais C
        • Thompson OJ
        • Cruz-Almeida Y
        • Fillingim RB
        The imperative for racial equality in pain science: A way forward.
        J Pain. 2021; 22: 1578-1585
        • Boutron I
        • Altman DG
        • Moher D
        • Schulz KF
        • Ravaud P
        CONSORT statement for randomized trials of nonpharmacologic treatments: A 2017 update and a CONSORT extension for nonpharmacologic trial abstracts.
        Ann Intern Med. 2017; 167 (American College of Physicians): 40-47
        • Braveman P
        • Gottlieb L
        The social determinants of health: It's time to consider the causes of the causes.
        Public Health Rep. 2014; 129: 19-31
        • Braveman PA
        • Kumanyika S
        • Fielding J
        • Laveist T
        • Borrell LN
        • Manderscheid R
        • Troutman A
        Health disparities and health equity: The issue is justice.
        Am J Public Health. 2011; 101 (2011/05/06. American Public Health Association. Available at:) (Accessed March 1, 2021.): S149-S155
        • Brooks Holliday S
        • Dubowitz T
        • Ghosh-Dastidar B
        • Beckman R
        • Buysse D
        • Hale L
        • Buman M
        • Troxel W
        Do sleep and psychological distress mediate the association between neighborhood factors and pain?.
        Pain Med. 2019; 20: 278-289
        • Campbell AD
        • Colombatti R
        • Andemariam B
        • Strunk C
        • Tartaglione I
        • Piccone CM
        • Manwani D
        • Asare EV
        • Boruchov D
        • Farooq F
        An analysis of racial and ethnic backgrounds within the CASiRe International Cohort of sickle cell disease patients: Implications for disease phenotype and clinical research.
        J Racial Ethn Health Disparities. 2021; 8 (Springer): 99-106
        • Ceballos RM
        • Knerr S
        • Scott MA
        • Hohl SD
        • Malen RC
        • Vilchis H
        • Thompson B
        Latino beliefs about biomedical research participation: A qualitative study on the U.S.-Mexico border.
        J Empir Res Hum Res Ethics. 2014; 9 (2014/08/05. Available at:) (Accessed March 1, 2021.): 10-21
        • Chandran A
        • Knapp E
        • Liu T
        • Dean LT
        A new era: Improving use of sociodemographic constructs in the analysis of pediatric cohort study data.
        Pediatr Res [Internet]. 2021; 90: 1132-1138
      1. congress.gov: US Constitution: Article I, section 2, clause 3. Available at: https://constitution.congress.gov/browse/essay/artI_S2_C3_1/ 2022. Accessed March 1, 2021.

        • Corbie-Smith GM
        Minority recruitment and participation in health research.
        N C Med J. 2004; 65 (United States): 385-387
        • Correa-De-Araujo R
        Serious gaps: How the lack of sex/gender-based research impairs health.
        J Womens Health (Larchmt). 2006; 15 (United States): 1116-1122
        • Crear-Perry J
        • Maybank A
        • Keeys M
        • Mitchell N
        • Godbolt D
        Moving towards anti-racist praxis in medicine.
        Lancet. 2020; 396 (Elsevier): 451-453
        • Cyrklaff M
        • Sanchez CP
        • Kilian N
        • Bisseye C
        • Simpore J
        • Frischknecht F
        • Lanzer M
        Hemoglobins S and C interfere with actin remodeling in Plasmodium falciparum-infected erythrocytes.
        Science. 2011; 334 (US): 1283-1286
        • Czéh B
        • Fuchs E
        • Wiborg O
        • Simon M
        Animal models of major depression and their clinical implications.
        Prog Neuro-Psychopharmacol Biol Psychiatry. 2016; 64 (Elsevier): 293-310
        • David RJ
        • Collins JWJ
        Bad outcomes in black babies: Race or racism?.
        Ethn Dis. 1991; 1 (United States): 236-244
        • Davis KD
        • Aghaeepour N
        • Ahn AH
        • Angst MS
        • Borsook D
        • Brenton A
        • Burczynski ME
        • Crean C
        • Edwards R
        • Gaudilliere B
        • Hergenroeder GW
        • Iadarola MJ
        • Iyengar S
        • Jiang Y
        • Kong J-T
        • Mackey S
        • Saab CY
        • Sang CN
        • Scholz J
        • Segerdahl M
        • Tracey I
        • Veasley C
        • Wang J
        • Wager TD
        • Wasan AD
        • Pelleymounter MA
        Discovery and validation of biomarkers to aid the development of safe and effective pain therapeutics: Challenges and opportunities.
        Nat Rev Neurol. 2020; 16 (2020/06/15. Nature Publishing Group UK. Available at:) (Accessed March 1, 2021.): 381-400
      2. Dictionary OE: “determinant, adj. and n.”. Available at: https://www.oed.com/view/Entry/51232?redirectedFrom=determinant 2022. Accessed March 1, 2021.

      3. Dictionary OE: “indicator, n.” Available at: https://www.oed.com/view/Entry/94420?redirectedFrom=indicator 2022. Accessed March 1, 2021.

        • Drevdahl DJ
        • Philips DA
        • Taylor JY
        Uncontested categories: The use of race and ethnicity variables in nursing research.
        Nurs Inq. 2006; 13 (Australia): 52-63
        • Driscoll AK
        • Ely DM
        Effects of changes in maternal age distribution and maternal age-specific infant mortality rates on infant mortality trends: United States, 2000-2017.
        Natl Vital Stat Rep. 2020; 69 (United States): 1-18
        • Ejiogu N
        • Norbeck JH
        • Mason MA
        • Cromwell BC
        • Zonderman AB
        • Evans MK
        Recruitment and retention strategies for minority or poor clinical research participants: Lessons from the healthy aging in neighborhoods of diversity across the life span study.
        Gerontologist [Internet]. 2011; 51 (Oxford University Press. Available at:): S33-S45
        • Engel GL
        The need for a new medical model: A challenge for biomedicine.
        Science. 1977; 196 (US): 129-136
        • Esoh K
        • Wonkam A
        Evolutionary history of sickle-cell mutation: Implications for global genetic medicine.
        Hum Mol Genet [Internet]. 2021; 30: R119-R128
        • Farooq F
        • Mogayzel PJ
        • Lanzkron S
        • Haywood C
        • Strouse JJ
        Comparison of US federal and foundation funding of research for sickle cell disease and cystic fibrosis and factors associated with research productivity.
        JAMA Netw Open [Internet]. 2020; 3: e201737https://doi.org/10.1001/jamanetworkopen.2020.1737
        • Feagin J
        • Bennefield Z
        Systemic racism and US health care.
        Soc Sci Med. 2014; 103: 7-14
        • Fenelon A
        • Chinn JJ
        • Anderson RN
        A comprehensive analysis of the mortality experience of hispanic subgroups in the United States: Variation by age, country of origin, and nativity.
        SSM - Popul Heal [Internet]. 2017; 3 (Available at:) (Accessed March 1, 2021.): 245-254
        • Fogelholm M
        • Leppinen S
        • Auvinen A
        • Raitanen J
        • Nuutinen A
        • Väänänen K
        Panel discussion does not improve reliability of peer review for medical research grant proposals.
        J Clin Epidemiol [Internet]. 2012; 65 (Available at:) (Accessed March 1, 2021.): 47-52
        • Ford CL
        • Airhihenbuwa CO
        Critical race theory, race equity, and public health: Toward antiracism praxis.
        Am J Public Health Am Public Health Assoc;. 2010; 100: S30-S35
        • Ford CL
        • CO Airhihenbuwa
        The public health critical race methodology: Praxis for antiracism research.
        Soc Sci Med [Internet]. 2010; 71 (Available at:) (Accessed March 1, 2021.): 1390-1398
        • Ford JG
        • Howerton MW
        • Lai GY
        • Gary TL
        • Bolen S
        • Gibbons MC
        • Tilburt J
        • Baffi C
        • Tanpitukpongse TP
        • Wilson RF
        • Powe NR
        • Bass EB
        Barriers to recruiting underrepresented populations to cancer clinical trials: A systematic review.
        Cancer. 2008; 112 (United States): 228-242
        • Fort DG
        • Herr TM
        • Shaw PL
        • Gutzman KE
        • Starren JB
        Mapping the evolving definitions of translational research.
        J Clin Transl Sci. 2017; 1 (Cambridge University Press): 60-66
        • Fraiman YS
        • Wojcik MH
        The influence of social determinants of health on the genetic diagnostic odyssey: Who remains undiagnosed, why, and to what effect?.
        Pediatr Res. 2021; 89 (2020/09/15. Available at:) (Accessed March 1, 2021.): 295-300
        • Frierson GM
        • Williams DM
        • Dunsiger S
        • Lewis BA
        • Whiteley JA
        • Albrecht AE
        • Jakicic JM
        • Horowitz SM
        • Marcus BH
        Recruitment of a racially and ethnically diverse sample into a physical activity efficacy trial.
        Clin Trials [Internet]. 2008; 5 (Available at:): 504-516
        • Fritz M
        • El Rawas R
        • Salti A
        • Klement S
        • Bardo MT
        • Kemmler G
        • Dechant G
        • Saria A
        • Zernig G
        Reversal of cocaine-conditioned place preference and mesocorticolimbic Zif268 expression by social interaction in rats.
        Addict Biol. 2011; 16 (Wiley Online Library): 273-284
        • Fuller-Thomson E
        • Brennenstuhl S
        • Hurd M
        Comparison of disability rates among older adults in aggregated and separate Asian American/Pacific Islander Subpopulations.
        Am J Public Health [Internet]. 2011; 101 (American Public Health Association): 94-100https://doi.org/10.2105/AJPH.2009.176784
        • Gage SH
        • Sumnall HR
        Rat park: How a rat paradise changed the narrative of addiction.
        Addiction. 2019; 114 (England): 917-922
        • Gatchel RJ
        • Peng YB
        • Peters ML
        • Fuchs PN
        • Turk DC
        The biopsychosocial approach to chronic pain: Scientific advances and future directions.
        Psychol Bull. 2007; 133 (United States): 581-624
        • Gee GC
        • Hing A
        • Mohammed S
        • Tabor DC
        • Williams DR
        Racism and the life course: Taking time seriously.
        Am J Public Health [Internet]. 2019; 109: S43-S47https://doi.org/10.2105/AJPH.2018.304766
        • Gehlert S
        • Sohmer D
        • Sacks T
        • Mininger C
        • McClintock M
        • Olopade O
        Targeting health disparities: A model linking upstream determinants to downstream interventions.
        Health Aff (Millwood). 2008; 27: 339-349
        • George S
        • Duran N
        • Norris K
        A systematic review of barriers and facilitators to minority research participation among African Americans, Latinos, Asian Americans, and Pacific Islanders.
        Am J Public Health Am Public Health Assoc;. 2014; 104: e16-e31
        • Germolec D
        • Kono DH
        • Pfau JC
        • Pollard KM
        Animal models used to examine the role of the environment in the development of autoimmune disease: Findings from an NIEHS Expert Panel Workshop.
        J Autoimmun. 2012; 39: 285-293
        • Glymour MM
        • Hamad R
        Causal thinking as a critical tool for eliminating social inequalities in health.
        Am J Public Health. 2018; 108: 623
        • Glymour MM
        • Spiegelman D
        Evaluating public health interventions: 5. Causal inference in public health research-do sex, race, and biological factors cause health outcomes?.
        Am J Public Health. 2017; 107 (2016/11/17. American Public Health Association. Available at:): 81-85
        • Golden SA
        • Covington HE
        • Berton O
        • Russo SJ
        A standardized protocol for repeated social defeat stress in mice.
        Nat Protoc [Internet]. 2011; 6: 1183-1191https://doi.org/10.1038/nprot.2011.361
        • Gordon KR
        Objectivity in science.
        Science (80-) [Internet]. 2006; 311 (Available at:): 1240LP-121241
      4. grants.nih.gov: NIH policy and guidelines on the inclusion of women and minorities as subjects in clinical research., 2001. Available at: https://grants.nih.gov/policy/inclusion/women-andminorities/guidelines.htm#:∼:text=TheNIHRevitalizationActof,andminoritiesinclinicalresearch.&text=Thestatuteincludesaspecific,and%2Cinparticularclinicaltrials. Accessed March 1, 2021.

        • Griffith DM
        • Johnson JL
        • Zhang R
        • Neighbors HW
        • Jackson JS
        Ethnicity, nativity, and the health of American Blacks.
        J Health Care Poor Underserved [Internet]. 2011; 22 (Available at:): 142-156
        • Guadagnolo BA
        • Cina K
        • Helbig P
        • Molloy K
        • Reiner M
        • Cook EF
        • Petereit DG
        Medical mistrust and less satisfaction with health care among Native Americans presenting for cancer treatment.
        J Health Care Poor Underserved [Internet]. 2009; 20 (Available at:) (Accessed March 1, 2021.): 210-226
        • Guillory JD
        The pro-slavery arguments of Dr. Samuel A. Cartwright.
        La Hist. 1968; 9 (JSTOR): 209-227
        • Hamilton TG
        • Hummer RA
        Immigration and the health of U.S. black adults: Does country of origin matter?.
        Soc Sci Med [Internet]. 2011; 73 (Available at:): 1551-1560
        • Hansen H
        • Parker C
        • Netherland J
        Race as a ghost variable in (white) opioid research.
        Sci Technol Hum Values. 2020; 45 (SAGE Publications Sage CA: Los Angeles, CA): 848-876
        • Harnett NG
        Neurobiological consequences of racial disparities and environmental risks: A critical gap in understanding psychiatric disorders.
        Neuropsychopharmacol. 2020; 45: 1247-1250
        • Harrell CJP
        • Burford TI
        • Cage BN
        • Nelson TM
        • Shearon S
        • Thompson A
        • Green S
        Multiple pathways linking racism to health outcomes.
        Du Bois Rev [Internet]. 2011; 8 (Available at:): 143-157
        • Harrell SP
        A multidimensional conceptualization of racism-related stress: Implications for the well-being of people of color.
        Am J Orthopsychiatry. 2000; 70 (United States): 42-57
        • Herrick C
        • Bell K
        Concepts, disciplines and politics: On ‘structural violence’ and the ‘social determinants of health.’.
        Crit Public Health. 2020; (Taylor & Francis): 1-14https://doi.org/10.1080/09581596.2020.1810637
        • Hochman A
        Racialization: A defense of the concept.
        Ethn Racial Stud. 2019; 42 (Taylor & Francis): 1245-1262
        • Hockham C
        • Bhatt S
        • Colah R
        • Mukherjee MB
        • Penman BS
        • Gupta S
        • Piel FB
        The spatial epidemiology of sickle-cell anaemia in India.
        Sci Rep [Internet]. 2018; 8: 17685
        • Hood AM
        • Booker SQ
        • Morais CA
        • Goodin BR
        • Letzen JE
        • Campbell LC
        • Merriwether EN
        • Aroke EN
        • Campbell CM
        • Mathur VA
        • Janevic MR
        Confronting racism in pain research: A shared commitment for engagement, diversity, and dissemination.
        J Pain. 2022; 23: 913-928
        • Jackson JW
        • VanderWeele TJ
        Decomposition analysis to identify intervention targets for reducing disparities.
        Epidemiology [Internet]. 2018; 29 (Available at:): 825-835
        • Janevic M
        • Mathur V
        • Booker S
        • Morais C
        • Meints S
        • Yeager K
        • Meghani S
        Making pain research more inclusive: Why and How.
        J Pain. 2022; 23: 707-728
        • Jones CP
        Invited commentary: “Race,” racism, and the practice of epidemiology.
        Am J Epidemiol [Internet]. 2001; 154: 299-304
        • Jones CP
        • LaVeist TA
        • Lillie-Blanton M
        Race” in the epidemiologic literature: An examination of the American Journal of Epidemiology, 1921-1990.
        Am J Epidemiol. 1991; 134 (United States): 1079-1084
        • Kalitzkus V
        • Matthiessen PF
        Narrative-based medicine: Potential, pitfalls, and practice.
        Perm J [Internet]. 2009; 13 (Available at:): 80-86
        • Kaplan JB
        • Bennett T
        Use of race and ethnicity in biomedical publication.
        JAMA [Internet]. 2003; 289: 2709-2716
        • Karran EL
        • Grant AR
        • Moseley GL
        Low back pain and the social determinants of health: A systematic review and narrative synthesis.
        Pain LWW. 2020; 161: 2476-2493
        • Kaufman JS
        • Cooper RS
        Commentary: Considerations for use of racial/ethnic classification in etiologic research.
        Am J Epidemiol [Internet]. 2001; 154: 291-298
      5. Kelly N, Zetzsche JO: Found in translation: How language shapes our lives and transforms the world. TarcherPerigee; 2012.

        • Kim AM
        • Tingen CM
        • Woodruff TK
        Sex bias in trials and treatment must end.
        Nature [Internet]. 2010; 465: 688-689
        • King L
        Black History as Anti-Racist and Non-Racist BT - But I Don’t See Color.
        in: Husband T The Perils, Practices, and Possibilities of Antiracist Education. SensePublishers, Rotterdam2016: 63-79
        • Kraus VB
        Biomarkers as drug development tools: Discovery, validation, qualification and use.
        Nat Rev Rheumatol. 2018; 14: 354-362
        • LaVeist TA
        Beyond dummy variables and sample selection: What health services researchers ought to know about race as a variable.
        Health Serv Res [Internet]. 1994; 29 (Available at:): 1-16
        • Lee SK
        Sex as an important biological variable in biomedical research.
        BMB Rep. 2018; 51 ([Internet] Korean Society for Biochemistry and Molecular Biology. Available at:) (Accessed March 1, 2021.): 167-173
        • Letzen JE
        • Mun CJ
        • Kuwabara H
        • Burton EF
        • Boring BL
        • Walls T
        • Speed TJ
        • Wong DF
        • Campbell CM
        Ethnic disparities in pain processing among healthy adults: Mu-opioid receptor binding potential as a putative mechanism.
        Pain. 2019; 161 (United States): 810-820
        • Levine DS
        • Taylor RJ
        • Nguyen AW
        • Chatters LM
        • Himle JA
        Family and friendship informal support networks and social anxiety disorder among African Americans and Black Caribbeans.
        Soc Psychiatry Psychiatr Epidemiol. 2015; 50 (2015/02/19. Available at:): 1121-1133
        • Losin EAR
        • Woo C-W
        • Medina NA
        • Andrews-Hanna JR
        • Eisenbarth H
        • Wager TD
        Neural and sociocultural mediators of ethnic differences in pain.
        Nat Hum Behav. 2020; 4: 1-14
        • Lukachko A
        • Hatzenbuehler ML
        • Keyes KM
        Structural racism and myocardial infarction in the United States.
        Soc Sci Med [Internet]. 2014; 103 (Available at:): 42-50
        • Lupien SJ
        • McEwen BS
        • Gunnar MR
        • Heim C
        Effects of stress throughout the lifespan on the brain, behaviour and cognition.
        Nat Rev Neurosci. 2009; 10: 434-445
        • Lyotard J-F
        The Postmodern Condition: A Report on Knowledge.
        U of Minnesota Press, 1984
        • Marmot M
        • Wilkinson R
        Social Determinants of Health.
        Oup Oxford, 2005
        • Mathur VA
        • Kiley KB
        • Haywood C
        • Bediako SM
        • Lanzkron S
        • Carroll CP
        • Buenaver LF
        • Pejsa M
        • Edwards RR
        • Haythornthwaite JA
        • Campbell CM
        Multiple levels of suffering: Discrimination in health-care settings is associated with enhanced laboratory pain sensitivity in sickle cell disease.
        Clin J Pain [Internet]. 2016; 32 (Lippincott Williams & Wilkins. Available at:): 1076-1085
        • Mathur VA
        • Trost Z
        • Ezenwa MO
        • Sturgeon JA
        • Hood AM
        Mechanisms of injustice: What we (don’t) know about racialized disparities in pain.
        Pain [Internet]. 2021; (Available at:)
        • Morais C
        • Aroke EN
        • Letzen JE
        • Campbell CM
        • Hood AM
        • Janevic MR
        • Mathur VA
        • Merriwether EN
        • Goodin BR
        • Booker SQ
        • Campbell LC
        Confronting Racism in Pain Research: A Call to Action.
        J Pain. 2022; 23: 878-892
        • Moscou S
        The conceptualization and operationalization of race and ethnicity by health services researchers.
        Nurs Inq. 2008; 15 (Australia): 94-105
        • Narayan MC
        Culture’s effects on pain assessment and management.
        AJN Am J Nurs [Internet]. 2010; 110 (Available at:) (Accessed March 1, 2021.): 38-47
        • Neisewander JL
        • Peartree NA
        • Pentkowski NS
        Emotional valence and context of social influences on drug abuse-related behavior in animal models of social stress and prosocial interaction.
        Psychopharmacology (Berl) [Internet]. 2012; 224: 33-56
        • Noltemeyer A
        • Grapin SL
        Working Together Towards Social Justice, Anti-racism, and Equity: A Joint Commitment From School Psychology International and Journal of Educational and Psychological Consultation.
        SAGE Publications Sage UK, London, England2020
        • Occa A
        • Morgan SE
        • Potter JE
        Underrepresentation of hispanics and other minorities in Clinical trials: Recruiters’ perspectives.
        J Racial Ethn Health Disparities. 2018; 5 (Switzerland): 322-332
        • Ong AD
        • Goktas S
        • Carrington Reid M
        More than hurt feelings: The wear and tear of day-to-day discrimination in adults with chronic pain.
        Pain Med. 2021; (England)
        • Paradies Y
        • Ben J
        • Denson N
        • Elias A
        • Priest N
        • Pieterse A
        • Gupta A
        • Kelaher M
        • Gee G
        Racism as a determinant of health: A systematic review and meta-analysis.
        PLoS One [Internet]. 2015; 10 (Public Library of Science e0138511. Available at:)
      6. Perry M, Shahidullah JD, Lynch MK: Moving towards cultural competence in the treatment of pediatric chronic pain, 2019.

        • Phinney JS
        When we talk about American ethnic groups, what do we mean?.
        Am Psychol Am Psychol Assoc. 1996; 51: 918
        • Pier EL
        • Brauer M
        • Filut A
        • Kaatz A
        • Raclaw J
        • Nathan MJ
        • Ford CE
        • Carnes M
        Low agreement among reviewers evaluating the same NIH grant applications.
        Proc Natl Acad Sci [Internet]. 2018; 115 (Available at:): 2952LP-292957
        • Plaut VC
        Diversity science: Why and how difference makes a difference.
        Psychol Inq [Internet]. 2010; 21: 77-99
        • Power-Hays A
        • McGann PT
        When actions speak louder than words — Racism and sickle cell disease.
        N Engl J Med [Internet]. 2020; 383: 1902-1903
        • Pratt B
        • Hixson L
        • Jones N
        Measuring Race and Ethnicity Across the Decades: 1790-2010.
        US Census Bur, Washington, DC2015 (Accessed March 1, 2021.)
        • Rassu FS
        • Luedke JC
        • Nanavaty N
        • Mathur VA
        • Meagher MW
        Greater mechanical temporal summation of pain in Latinx-Americans and the role of adverse life experiences.
        Pain Rep. 2020; 5: e842
        • Read JG
        • Lynch SM
        • West JS
        Disaggregating heterogeneity among non-Hispanic whites: Evidence and implications for U.S. racial/ethnic health disparities.
        Popul Res Policy Rev [Internet]. 2021; 40: 9-31
        • Research NI of H (US). O of E, Committee NIHON
        Committee NIHT: Outreach Notebook for the Inclusion, Recruitment and Retention of Women and Minority Subjects in Clinical Research: Principal Investigators’ Notebook.
        National Institutes of Health, Office of Research on Women’s Health, 2002
        • Riche MF
        Cultural and political dimensions of the U.S. census: Past and present.
        Am Behav Sci [Internet]. 1999; 42: 933-945
        • Rickford JR
        Raciolinguistics: How Language Shapes Our Ideas About Race.
        Oxford University Press, 2016
        • Riley WT
        • Greene-Schloesser D
        • Blachman-Demner DR
        • Spittel M
        Twenty-five years of the national institutes of health office of behavioral and social sciences research.
        Transl Behav Med [Internet]. 2020; 10: 1243-1248
        • Roberts D
        Fatal Invention: How Science, Politics, and Big Business Re-create Race in the Twenty-First Century.
        New Press/ORIM, 2011
        • Robinson-Lane SG
        • Booker SQ
        Culturally responsive pain management for black older adults.
        J Gerontol Nurs. 2017; : 1-8
        • Ross PT
        • Hart-Johnson T
        • Santen SA
        • Zaidi NLB
        Considerations for using race and ethnicity as quantitative variables in medical education research.
        Perspect Med Educ [Internet]. 2020; 9 (Bohn Stafleu van Loghum. Available at:): 318-323
        • Sakoda RT
        • Simes JT
        Solitary confinement and the U.S. prison boom.
        Crim Justice Policy Rev [Internet]. 2019; 32: 66-102
        • Salerno J
        • Bogard K
        What do social determinants of health determine?.
        J Urban Heal [Internet]. 2019; 96: 793-794
        • Salter PS
        • Adams G
        • Perez MJ
        Racism in the structure of everyday worlds: A cultural-psychological perspective.
        Curr Dir Psychol Sci. 2018; 27 (Sage Publications Sage CA: Los Angeles, CA): 150-155
        • Schmotzer GL
        Barriers and facilitators to participation of minorities in clinical trials.
        Ethn Dis. 2012; 22 (United States): 226-230
        • Schrewe B
        From history to myth: Productive engagement with the Flexnerian metanarrative in medical education.
        Adv Heal Sci Educ [Internet]. 2013; 18: 1121-1138
      7. Sewell AA, Stewart QT: Quantifying race: On methods for analyzing social inequality, Rethinking Race and Ethnicity in Research Methods, Stanfield JH, II, Routledge; New York, 2021, pp 209–234

        • Sewell AA
        The Racism-Race Reification Process: A Mesolevel Political Economic Framework for Understanding Racial Health Disparities. 2. Sociol Race Ethn SAGE Publications Sage CA, Los Angeles, CA2016: 402-432
        • Sial OK
        • Warren BL
        • Alcantara LF
        • Parise EM
        • Bolaños-Guzmán CA
        Vicarious social defeat stress: Bridging the gap between physical and emotional stress.
        J Neurosci Methods. 2016; 258 (Available at:): 94-103
        • Stachulski F
        Prison gerrymandering: Locking up elections and diluting representational equality.
        U Ill L Rev Hein. 2019; 401 (Online): 401-428
        • Sullivan S
        Inheriting racist disparities in health: Epigenetics and the transgenerational effects of white racism.
        Crit Philos Race. 2013; 1 (JSTOR): 190-218
        • Thomas SB
        • Quinn SC
        • Butler J
        • Fryer CS
        • Garza MA
        Toward a fourth generation of disparities research to achieve health equity.
        Annu Rev Public Health. 2011; 32: 399-416
        • Truong M
        • Sharif MZ
        We’re in this together: A reflection on how bioethics and public health can collectively advance scientific efforts towards addressing racism.
        J Bioeth Inq [Internet]. 2021; https://doi.org/10.1007/s11673-020-10069-w
        • Turk DC
        • Monarch ES
        Biopsychosocial Perspective on Chronic Pain.
        Guilford Press, 2002
        • Umscheid CA
        • Margolis DJ
        • Grossman CE
        Key concepts of clinical trials: A narrative review.
        Postgrad Med. 2011; 123: 194-204
        • Vespa J
        • Armstrong DM
        • Medina L
        Demographic Turning Points for the United States: Population Projections for 2020 to 2060.
        US Department of Commerce, Economics and Statistics Administration, US, 2018
        • Walker RJ
        • Smalls BL
        • Egede LE
        Social determinants of health in adults with type 2 diabetes–Contribution of mutable and immutable factors.
        Diabetes Res Clin Pract. 2015; 110 (Available at:) (Accessed March 1, 2021.): 193-201
        • Waller R
        • Smith AJ
        • O'Sullivan PB
        • Slater H
        • Sterling M
        • Straker LM
        The association of early life stressors with pain sensitivity and pain experience at 22 years.
        Pain. 2020; 161 (United States): 220-229
        • White J
        • Tannenbaum C
        • Klinge I
        • Schiebinger L
        • Clayton J
        The integration of sex and gender considerations into biomedical research: Lessons from international funding agencies.
        J Clin Endocrinol Metab. 2021; 106: 3034-3048
        • Williams DR
        • Sternthal M
        Understanding racial-ethnic disparities in health: Sociological contributions.
        J Health Soc Behav [Internet]. 2010; 51 (Suppl. Available at:): S15-S27
        • You DS
        • Albu S
        • Lisenbardt H
        • Meagher MW
        Cumulative childhood adversity as a risk factor for common chronic pain conditions in young adults.
        Pain Med. 2019; 20: 486-494
        • Zarbin M
        What constitutes translational research? Implications for the scope of translational vision science and technology.
        Transl Vis Sci Technol. 2022; 9222020

      Linked Article

      • Confronting Racism in Pain Research: A Call to Action
        The Journal of PainVol. 23Issue 6
        • Preview
          Racism is an established health determinant across the world. In this 3-part series, we argue that a disregard of how racism manifests in pain research practices perpetuates pain inequities and slows the progression of the field. Our goal in part-1 is to provide a historical and theoretical background of racism as a foundation for understanding how an antiracism pain research framework - which focuses on the impact of racism, rather than “race,” on pain outcomes - can be incorporated across the continuum of pain research.
        • Full-Text
        • PDF
      • Confronting Racism in All Forms of Pain Research: A Shared Commitment for Engagement, Diversity, and Dissemination
        The Journal of PainVol. 23Issue 6
        • Preview
          This third paper in the “Confronting Racism in All Forms of Pain Research” series discusses adopting an antiracism framework across all pain research disciplines and highlights the significant benefits of doing so. We build upon the previous call to action and the proposed reframing of study designs articulated in the other papers in the series and seek to confront and eradicate racism through a shared commitment to change current research practices. Specifically, we emphasize the systematic disadvantage created by racialization (ie, the Eurocentric social and political process of ascribing racialized identities to a relationship, social practice, or group) and discuss how engaging communities in partnership can increase the participation of racialized groups in research studies and enrich the knowledge gained.
        • Full-Text
        • PDF