Advertisement

The Relationship Between Adverse Life Events and Endogenous Inhibition of Pain and Spinal Nociception: Findings From the Oklahoma Study of Native American Pain Risk (OK-SNAP)

      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

      To read this article in full you will need to make a payment
      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Anda RF
        • Felitti VJ
        • Bremner JD
        • Walker JD
        • Whitfield C
        • Perry BD
        • Dube SR
        • Giles WH
        The enduring effects of abuse and related adverse experiences in childhood.
        Eur Arch Psychiatry Clin Neurosci. 2006; 256: 174-186
        • Apkarian AV
        • Bushnell MC
        • Treede R-D
        • Zubieta J-K
        Human brain mechanisms of pain perception and regulation in health and disease.
        Eur J Pain. 2005; 9: 463-484
        • Berens AE
        • Jensen SKG
        • Nelson 3rd, CA
        Biological embedding of childhood adversity: From physiological mechanisms to clinical implications.
        BMC Med. 2017; 15: 135
        • Blake DD
        • Weathers FW
        • Nagy LM
        • Kaloupek DG
        • Gusman FD
        • Charney DS
        • Keane TM
        The development of a clinician-administered PTSD scale.
        J Trauma Stress. 1995; 8: 75-90
        • Buysse DJ
        • Reynolds CF
        • Monk TH
        • Berman SR
        • Kupfer DJ
        The pittsburgh sleep quality index (PSQI): A new instrument for psychiatric research and practice.
        Psychiatry Res. 1989; 28: 193-213
        • Campbell CM
        • France CR
        • Robinson ME
        • Logan HL
        • Geffken GR
        • Fillingim RB
        Ethnic differences in diffuse noxious inhibitory controls.
        J Pain. 2008; 9: 759-766
        • Chan CW
        • Dallaire M
        Subjective pain sensation is linearly correlated with the flexion reflex in man.
        Brain Res. 1989; 479: 145-150
        • Cohen S
        • Kamarck T
        • Mermelstein R
        Perceived stress scale.
        Meas Stress Guide Health Soc Sci. 1994; 10: 1-2
        • Corder G
        • Doolen S
        • Donahue RR
        • Winter MK
        • Jutras BL
        • He Y
        • Hu X
        • Wieskopf J
        • Mogil J
        • Storm D
        Constitutive μ-opioid receptor activity leads to long-term endogenous analgesia and dependence.
        Science. 2013; 341: 1394-1399
        • Danziger N
        • Fournier E
        • Bouhassira D
        • Michaud D
        • De Broucker T
        • Santarcangelo E
        • Carli G
        • Chertock L
        • Willer JC
        Different strategies of modulation can be operative during hypnotic analgesia: a neurophysiological study.
        Pain. 1998; 75: 85-92
        • Derogatis LR
        SCL-90-R : Symptom Checklist-90-R : Administration, Scoring & Procedures Manual.
        National Computer Systems, Inc., Minneapolis, Minn.1994
        • Dhondt E
        • Van Oosterwijck S
        • Coppieters I
        • Danneels L
        • Van Oosterwijck J
        Effects of conditioned pain modulation on the nociceptive flexion reflex in healthy people.
        Clin J Pain. 2019; 35: 794-807
        • Dube SR
        • Anda RF
        • Felitti VJ
        • Chapman DP
        • Williamson DF
        • Giles WH
        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
        • Emery CF
        • France CR
        • Harris J
        • Norman G
        • Vanarsdalen C
        Effects of progressive muscle relaxation training on nociceptive flexion reflex threshold in healthy young adults: A randomized trial.
        Pain. 2008; 138: 375-379
        • Emery CF
        • Keefe FJ
        • France CR
        • Affleck G
        • Waters S
        • Fondow MD
        • McKee DC
        • France JL
        • Hackshaw KV
        • Caldwell DS
        • Stainbrook D
        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
        • Felitti VJ
        • Anda RF
        • Nordenberg D
        • Williamson DF
        • Spitz AM
        • Edwards V
        • Koss MP
        • Marks JS
        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
        • Flouri E
        • Kallis C
        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
        • Fox SE
        • Levitt P
        • Nelson III, CA
        How the timing and quality of early experiences influence the development of brain architecture.
        Child Dev. 2010; 81: 28-40
        • Gray MJ
        • Litz BT
        • Hsu JL
        • Lombardo TW
        Psychometric properties of the life events checklist.
        Assessment. 2004; 11: 330-341
        • Guieu R
        • Blin P
        • Pouget J
        • Serratrice G
        High level sportsmen and nociceptive flexion reflex of the lower limb.
        Can J Neurosci. 1992; 19: 69-71
        • Hellman N
        • Kuhn BL
        • Lannon EW
        • Payne MF
        • Sturycz CA
        • Palit S
        • Shadlow JO
        • Rhudy JL
        Emotional modulation of pain and spinal nociception in sexual assault survivors.
        Psychosom Med. 2018; 80: 861-868
        • Hellman N
        • Sturycz CA
        • Lannon EW
        • Kuhn BL
        • Güereca YM
        • Toledo TA
        • Payne MF
        • Huber FA
        • Demuth M
        • Palit S
        • Shadlow JO
        • Rhudy JL
        Conditioned pain modulation in sexual assault survivors.
        J Pain. 2019; 20: 1027-1039
        • Huber F
        • Kuhn B
        • Lannon E
        • Sturycz C
        • Payne M
        • Hellman N
        • Toledo T
        • Guereca Y
        • DeMuth M
        • Palit S
        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
        • Huber FA
        • Kell PA
        • Kuhn BL
        • Lannon EW
        • Palit S
        • Payne MF
        • Hellman N
        • Sturycz CA
        • Güereca YM
        • Toledo TA
        • Demuth MJ
        • Hahn BJ
        • Shadlow JO
        • Rhudy JL
        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
        • Jimenez N
        • Garroutte E
        • Kundu A
        • Morales L
        • Buchwald D
        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
        • Kennedy DL
        • Kemp HI
        • Ridout D
        • Yarnitsky D
        • Rice AS
        Reliability of conditioned pain modulation: A systematic review.
        Pain. 2016; 157: 2410
        • Landau R
        • Kraft JC
        • Flint LY
        • Carvalho B
        • Richebé P
        • Cardoso M
        • Lavand'homme P
        • Granot M
        • Yarnitsky D
        • Cahana A
        An experimental paradigm for the prediction of post-operative pain (PPOP).
        J Vis Exp Jove. 2010; 35: 1671
        • Larivière M
        • Goffaux P
        • Marchand S
        • Julien N
        Changes in pain perception and descending inhibitory controls start at middle age in healthy adults.
        Clin J Pain. 2007; 23: 506-510
        • Le Bars D
        • Willer J-C
        Diffuse noxious inhibitory controls (DNIC).
        Senses Compr Ref. 2010; 5: 762-773
        • Le Roy C
        • Laboureyras E
        • Gavello-Baudy S
        • Chateauraynaud J
        • Laulin J-P
        • Simonnet G
        Endogenous opioids released during non-nociceptive environmental stress induce latent pain sensitization Via a NMDA-dependent process.
        J Pain. 2011; 12: 1069-1079
        • Lin JE
        • Neylan TC
        • Epel E
        • O'Donovan A
        Associations of childhood adversity and adulthood trauma with C-reactive protein: A cross-sectional population-based study.
        Brain Behav Immun. 2016; 53: 105-112
        • Manresa JAB
        • Fritsche R
        • Vuilleumier PH
        • Oehler C
        • Mørch CD
        • Arendt-Nielsen L
        • Andersen OK
        • Curatolo M
        Is the conditioned pain modulation paradigm reliable? A test-retest assessment using the nociceptive withdrawal reflex.
        PloS One. 2014; 9e100241
        • Manson SM
        • Beals J
        • Klein SA
        • Croy CD
        Ai-superpfp team: Social epidemiology of trauma among 2 American Indian reservation populations.
        Am J Public Health. 2005; 95: 851-859
        • Martel MO
        • Wasan AD
        • Edwards RR
        Sex differences in the stability of conditioned pain modulation (CPM) among patients with chronic pain.
        Pain Med. 2013; 14: 1757-1768
        • Marvizon JC
        • Walwyn W
        • Minasyan A
        • Chen W
        • Taylor BK
        Latent sensitization: a model for stress-sensitive chronic pain.
        Curr Protoc Neurosci. 2015; 71: 9.50.1-9.50.14
        • McLaughlin KA
        • Koenen KC
        • Hill ED
        • Petukhova M
        • Sampson NA
        • Zaslavsky AM
        • Kessler RC
        Trauma exposure and posttraumatic stress disorder in a national sample of adolescents.
        J Am Acad Child Adolesc Psychiatry. 2013; 52: 815-830
        • Mendell LM
        • Wall PD
        Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres.
        Nature. 1965; 206: 97
        • Mossey JM
        Defining racial and ethnic disparities in pain management.
        Clin Orthop Relat Res. 2011; 469: 1859-1870
        • Ossipov MH
        • Morimura K
        • Porreca F
        Descending pain modulation and chronification of pain.
        Curr Opin Support Palliat Care. 2014; 8: 143
        • Petersen-Felix S
        • Arendt-Nielsen L
        • Bak P
        • Roth D
        • Fischer M
        • Bjerring P
        • Zbinden AM
        Analgesic effect in humans of subanaesthetic isoflurane concentrations evaluated by experimentally induced pain.
        Br J Anaesthesiol. 1995; 75: 55-60
        • Piché M
        • Arsenault M
        • Rainville P
        Cerebral and cerebrospinal processes underlying counterirritation analgesia.
        J Neurosci. 2009; 29: 14236-14246
        • Preacher KJ
        • Curran PJ
        • Bauer DJ
        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
        • Prinz U
        • Nutzinger DO
        • Schulz H
        • Petermann F
        • Braukhaus C
        • Andreas S
        Comparative psychometric analyses of the SCL-90-R and its short versions in patients with affective disorders.
        BMC Psychiatry. 2013; 13: 104
        • Reichling DB
        • Levine JD
        Critical role of nociceptor plasticity in chronic pain.
        Trends Neurosci. 2009; 32: 611-618
        • Reyes-Gibby CC
        • Aday LA
        • Todd KH
        • Cleeland CS
        • Anderson KO
        Pain in aging community-dwelling adults in the United States: Non-Hispanic whites, non-Hispanic blacks, and Hispanics.
        J Pain. 2007; 8: 75-84
        • Rhudy JL
        • France CR
        Defining the nociceptive flexion reflex (NFR) threshold in human participants: A comparison of different scoring criteria.
        Pain. 2007; 128: 244-253
        • Rhudy JL
        • France CR
        • Bartley EJ
        • McCabe KM
        • Williams AE
        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
        • Rhudy JL
        • Hellman N
        • Sturycz CA
        • Toledo TA
        • Palit S
        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
        • Rhudy JL
        • Lannon EW
        • Kuhn BL
        • Palit S
        • Payne MF
        • Sturycz CA
        • Hellman N
        • Güereca YM
        • Toledo TA
        • Coleman HB
        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
        • Rhudy JL
        • Lannon EW
        • Kuhn BL
        • Palit S
        • Payne MF
        • Sturycz CA
        • Hellman N
        • Güereca YM
        • Toledo TA
        • Huber FA
        • Demuth MJ
        • Hahn BJ
        • Chaney JM
        • Shadlow JO
        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
        • Robinson ME
        • Myers CD
        • Sadler IJ
        • Riley JLI
        • Kvaal SA
        • Geisser ME
        Bias effects in three common self-report pain assessment measures.
        Clin J Pain. 1997; 13: 74-81
        • Sachs-Ericsson N
        • Kendall-Tackett K
        • Hernandez A
        Childhood abuse, chronic pain, and depression in the National Comorbidity Survey.
        Child Abuse Negl. 2007; 31: 531-547
        • Slopen N
        • Shonkoff JP
        • Albert MA
        • Yoshikawa H
        • Jacobs A
        • Stoltz R
        • Williams DR
        Racial disparities in child adversity in the US: Interactions with family immigration history and income.
        Am J Prev Med. 2016; 50: 47-56
        • Smith AK
        • Conneely KN
        • Kilaru V
        • Mercer KB
        • Weiss TE
        • Bradley B
        • Tang Y
        • Gillespie CF
        • Cubells JF
        • Ressler KJ
        Differential immune system DNA methylation and cytokine regulation in post-traumatic stress disorder.
        Am J Med Genet B Neuropsychiatr Genet. 2011; 156: 700-708
        • Sturycz C
        • Hellman N
        • Payne M
        • Kuhn B
        • Hahn B
        • Lannon E
        • Palit S
        • Güereca Y
        • Toledo T
        • Shadlow J
        • Rhudy J
        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
        • Taylor B
        • Corder G
        Endogenous analgesia, dependence, and latent pain sensitization.
        Curr Top Behav Neurosci. 2014; 20: 283-325
        • Toledo TA
        • Kuhn BL
        • Payne MF
        • Lannon EW
        • Palit S
        • Sturycz CA
        • Hellman N
        • Güereca YM
        • Demuth MJ
        • Huber F
        • Shadlow JO
        • Rhudy JL
        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
        • Tracey I
        • Mantyh PW
        The cerebral signature for pain perception and its modulation.
        Neuron. 2007; 55: 377-391
        • Walsh K
        • Galea S
        • Koenen KC
        Mechanisms underlying sexual violence exposure and psychosocial sequelae: A theoretical and empirical review.
        Clin Psychol Sci Pract. 2012; 19: 260-275
        • Ware JE
        • Snow KK
        • Kosinski M
        • Gandek B
        SF-36 Health Survey Manual and Interpretation Guide.
        The Health Institute New England Medical Center, Boston1993
        • Wilcox RR
        Understanding and Applying Basic Statistical Methods Using R.
        John Wiley & Sons, 2016
        • Wilder-Smith OH
        • Schreyer T
        • Scheffer GJ
        • Arendt-Nielsen L
        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
        • Willer JC
        Comparative study of perceived pain and nociceptive flexion reflex in man.
        Pain. 1977; 3: 69-80
        • Woolf CJ
        • Thompson SW
        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
        • Yarnitsky D
        • Crispel Y
        • Eisenberg E
        • Granovsky Y
        Prediction of chronic post-operative pain: pre-operative DNIC testing identifies patients at risk.
        Pain. 2008; 138: 22-28
        • Yarnitsky D
        • Granot M
        • Granovsky Y
        Pain modulation profile and pain therapy: Between pro-and antinociception.
        Pain. 2014; 155: 663-665
        • 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 Malden Mass. 2019; 20: 486-494
        • You DS
        • Creech SK
        • Meagher MW
        Enhanced area of secondary hyperalgesia in women with multiple stressful life events: A pilot study.
        Pain Med. 2016; 17: 1859-1864
        • You DS
        • Meagher MW
        Childhood adversity and pain facilitation.
        Psychosom Med. 2018; 80: 869-879
        • You DS
        • Meagher MW
        Childhood adversity and pain sensitization.
        Psychosom Med. 2016; 78: 1084-1093