Highlights
- •Native Americans (NAs) are at higher risk for chronic pain than other ethnic groups
- •NAs report more adverse life events (ALEs), which are associated with pain risk
- •The mechanism(s) by which ALEs confer pain risk are not fully understood
- •ALEs were associated with impaired descending inhibition of spinal nociception
- •The effect of ALEs was not moderated by ethnicity
Abstract
Adverse life events (ALEs) are a risk factor for chronic pain; however, mechanisms
underlying this association are not understood. This study examined whether cumulative
ALE exposure impairs endogenous inhibition of pain (assessed from pain report) and
spinal nociception (assessed from nociceptive flexion reflex; NFR) in healthy, pain-free
Native Americans (n = 124) and non-Hispanic Whites (n = 129) during a conditioned
pain modulation (CPM) task. Cumulative ALE exposure was assessed prior to testing
by summing the number of potentially traumatic events experienced by each participant
across their lifespan. Multilevel modeling found that ALEs were associated with NFR
modulation during the CPM task even after controlling for general health, body mass
index, sex, age, blood pressure, sleep quality, stimulation intensity, stimulus number,
perceived stress, and psychological distress. Low exposure to ALEs was associated
with NFR inhibition, whereas high exposure to ALEs was associated with NFR facilitation.
By contrast, pain perception was inhibited during the CPM task regardless of the level
of ALE exposure. Race/ethnicity did not moderate these results. Thus, ALEs may be
pronociceptive for both Native Americans and non-Hispanic Whites by impairing descending
inhibition of spinal nociception. This could contribute to a chronic pain risk phenotype
involving latent spinal sensitization.
Perspective
This study found that adverse life events were associated with impaired descending
inhibition of spinal nociception in a sample of Native Americans and non-Hispanic
Whites. These findings expand on previous research linking adversity to chronic pain
risk by identifying a proximate physiological mechanism for this association.
Key words
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References
- The enduring effects of abuse and related adverse experiences in childhood.Eur Arch Psychiatry Clin Neurosci. 2006; 256: 174-186
- Human brain mechanisms of pain perception and regulation in health and disease.Eur J Pain. 2005; 9: 463-484
- Biological embedding of childhood adversity: From physiological mechanisms to clinical implications.BMC Med. 2017; 15: 135
- The development of a clinician-administered PTSD scale.J Trauma Stress. 1995; 8: 75-90
- The pittsburgh sleep quality index (PSQI): A new instrument for psychiatric research and practice.Psychiatry Res. 1989; 28: 193-213
- Ethnic differences in diffuse noxious inhibitory controls.J Pain. 2008; 9: 759-766
- Subjective pain sensation is linearly correlated with the flexion reflex in man.Brain Res. 1989; 479: 145-150
- Perceived stress scale.Meas Stress Guide Health Soc Sci. 1994; 10: 1-2
- Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence.Science. 2013; 341: 1394-1399
- Different strategies of modulation can be operative during hypnotic analgesia: a neurophysiological study.Pain. 1998; 75: 85-92
- SCL-90-R : Symptom Checklist-90-R : Administration, Scoring & Procedures Manual.National Computer Systems, Inc., Minneapolis, Minn.1994
- Effects of conditioned pain modulation on the nociceptive flexion reflex in healthy people.Clin J Pain. 2019; 35: 794-807
- Childhood abuse, household dysfunction, and the risk of attempted suicide throughout the life span findings from the adverse childhood experiences study.JAMA. 2001; 286: 3089-3096
- Effects of progressive muscle relaxation training on nociceptive flexion reflex threshold in healthy young adults: A randomized trial.Pain. 2008; 138: 375-379
- Effects of a brief coping skills training intervention on nociceptive flexion reflex threshold in patients having osteoarthritic knee pain: A preliminary laboratory study of sex differences.J Pain Symptom Manage. 2006; 31: 262-269
- Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: The adverse childhood experiences (ACE) study.Am J Prev Med. 1998; 14: 245-258
- Adverse life events and psychopathology and prosocial behavior in late adolescence: testing the timing, specificity, accumulation, gradient, and moderation of contextual risk.J Am Acad Child Adolesc Psychiatry. 2007; 46: 1651-1659
- How the timing and quality of early experiences influence the development of brain architecture.Child Dev. 2010; 81: 28-40
- Psychometric properties of the life events checklist.Assessment. 2004; 11: 330-341
- High level sportsmen and nociceptive flexion reflex of the lower limb.Can J Neurosci. 1992; 19: 69-71
- Emotional modulation of pain and spinal nociception in sexual assault survivors.Psychosom Med. 2018; 80: 861-868
- Conditioned pain modulation in sexual assault survivors.J Pain. 2019; 20: 1027-1039
- Less efficient endogenous inhibition of spinal nociception predicts chronic pain onset: A prospective analysis from the Oklahoma Study of Native American Pain Risk (OK-SNAP).Am Pain Soc. 2019; 20: S40
- The association between adverse life events, psychological stress, and pain-promoting affect and cognitions in native Americans: Results from the Oklahoma Study of Native American Pain Risk.J Racial Ethn Health Disparities. 2021; https://doi.org/10.1007/s40615-020-00945-x
- A review of the experience, epidemiology, and management of pain among American Indian, Alaska Native, and Aboriginal Canadian Peoples.J Pain. 2011; 12: 511-522
- Reliability of conditioned pain modulation: A systematic review.Pain. 2016; 157: 2410
- An experimental paradigm for the prediction of post-operative pain (PPOP).J Vis Exp Jove. 2010; 35: 1671
- Changes in pain perception and descending inhibitory controls start at middle age in healthy adults.Clin J Pain. 2007; 23: 506-510
- Diffuse noxious inhibitory controls (DNIC).Senses Compr Ref. 2010; 5: 762-773
- Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process.J Pain. 2011; 12: 1069-1079
- Associations of childhood adversity and adulthood trauma with C-reactive protein: A cross-sectional population-based study.Brain Behav Immun. 2016; 53: 105-112
- Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex.PloS One. 2014; 9e100241
- Ai-superpfp team: Social epidemiology of trauma among 2 American Indian reservation populations.Am J Public Health. 2005; 95: 851-859
- Sex differences in the stability of conditioned pain modulation (CPM) among patients with chronic pain.Pain Med. 2013; 14: 1757-1768
- Latent sensitization: a model for stress-sensitive chronic pain.Curr Protoc Neurosci. 2015; 71: 9.50.1-9.50.14
- Trauma exposure and posttraumatic stress disorder in a national sample of adolescents.J Am Acad Child Adolesc Psychiatry. 2013; 52: 815-830
- Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres.Nature. 1965; 206: 97
- Defining racial and ethnic disparities in pain management.Clin Orthop Relat Res. 2011; 469: 1859-1870
- Descending pain modulation and chronification of pain.Curr Opin Support Palliat Care. 2014; 8: 143
- Analgesic effect in humans of subanaesthetic isoflurane concentrations evaluated by experimentally induced pain.Br J Anaesthesiol. 1995; 75: 55-60
- Cerebral and cerebrospinal processes underlying counterirritation analgesia.J Neurosci. 2009; 29: 14236-14246
- Computational tools for probing interactions in multiple linear regression, multilevel modeling, and latent curve analysis.J Educ Behav Stat. 2006; 31 (Sage Publications Sage CA: Los Angeles, CA): 437-448
- Comparative psychometric analyses of the SCL-90-R and its short versions in patients with affective disorders.BMC Psychiatry. 2013; 13: 104
- Critical role of nociceptor plasticity in chronic pain.Trends Neurosci. 2009; 32: 611-618
- Pain in aging community-dwelling adults in the United States: Non-Hispanic whites, non-Hispanic blacks, and Hispanics.J Pain. 2007; 8: 75-84
- Defining the nociceptive flexion reflex (NFR) threshold in human participants: A comparison of different scoring criteria.Pain. 2007; 128: 244-253
- Psychophysiological responses to pain: Further validation of the nociceptive flexion reflex (NFR) as a measure of nociception using multilevel modeling.Psychophysiology. 2009; 46: 939-948
- Modified biofeedback (conditioned biofeedback) promotes antinociception by increasing the nociceptive flexion reflex threshold and reducing temporal summation of pain: A controlled trial.J Pain. 2019; 21: 663-676
- Sensory, affective, and catastrophizing reactions to multiple stimulus modalities: Results from the Oklahoma study of native American pain risk.J Pain. 2019; 20: 965-979
- Assessing peripheral fibers, pain sensitivity, central sensitization, and descending inhibition in Native Americans: Main findings from the Oklahoma Study of Native American Pain Risk.Pain. 2020; 161: 388-404
- Bias effects in three common self-report pain assessment measures.Clin J Pain. 1997; 13: 74-81
- Childhood abuse, chronic pain, and depression in the National Comorbidity Survey.Child Abuse Negl. 2007; 31: 531-547
- Racial disparities in child adversity in the US: Interactions with family immigration history and income.Am J Prev Med. 2016; 50: 47-56
- Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder.Am J Med Genet B Neuropsychiatr Genet. 2011; 156: 700-708
- Race/ethnicity does not moderate the relationship between adverse life experiences and temporal summation of the nociceptive flexion reflex and pain: Results from the Oklahoma Study of Native American Pain Risk (OK-SNAP).J Pain. 2019; 20: 941-955
- Endogenous analgesia, dependence, and latent pain sensitization.Curr Top Behav Neurosci. 2014; 20: 283-325
- The effect of pain catastrophizing on endogenous inhibition of pain and spinal nociception in Native Americans: Results from the Oklahoma Study of Native American Pain Risk.Ann Behav Med. 2020; 54: 575-594
- The cerebral signature for pain perception and its modulation.Neuron. 2007; 55: 377-391
- Mechanisms underlying sexual violence exposure and psychosocial sequelae: A theoretical and empirical review.Clin Psychol Sci Pract. 2012; 19: 260-275
- SF-36 Health Survey Manual and Interpretation Guide.The Health Institute New England Medical Center, Boston1993
- Understanding and Applying Basic Statistical Methods Using R.John Wiley & Sons, 2016
- Patients with chronic pain after abdominal surgery show less preoperative endogenous pain inhibition and more postoperative hyperalgesia: A pilot study.J Pain Palliat Care Pharmacother. 2010; 24: 119-128
- Comparative study of perceived pain and nociceptive flexion reflex in man.Pain. 1977; 3: 69-80
- The induction and maintenance of central sensitization is dependent on N-methyl-D-aspartic acid receptor activation; implications for the treatment of post-injury pain hypersensitivity states.Pain. 1991; 44: 293-299
- Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.Pain. 2008; 138: 22-28
- Pain modulation profile and pain therapy: Between pro-and antinociception.Pain. 2014; 155: 663-665
- Cumulative childhood adversity as a risk factor for common chronic pain conditions in young adults.Pain Med Malden Mass. 2019; 20: 486-494
- Enhanced area of secondary hyperalgesia in women with multiple stressful life events: A pilot study.Pain Med. 2016; 17: 1859-1864
- Childhood adversity and pain facilitation.Psychosom Med. 2018; 80: 869-879
- Childhood adversity and pain sensitization.Psychosom Med. 2016; 78: 1084-1093
Article info
Publication history
Published online: April 02, 2021
Accepted:
March 12,
2021
Received in revised form:
March 9,
2021
Received:
October 29,
2020
Footnotes
This research was supported by the National Institute on Minority Health and Health Disparities of the National Institute of Health under Award Number R01MD007807. Edward Lannon was supported by a National Science Foundation Graduate Research Fellowship Program and is currently funded by a T32 from the National Institute On Drug Abuse (T32DA035165). The content is solely the responsibility of the authors and does not necessarily reflect the views of the National Institutes of Health, National Science Foundation, Indian Health Service, or the Cherokee Nation. Aspects of this research have been presented at the International Association for the 2020 American Psychosomatic Society conference.
The authors report no conflicts of interest.
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© 2021 by United States Association for the Study of Pain, Inc.
