Abstract
Adverse life experiences (ALEs) are associated with hyperalgesia and chronic pain,
but the underlying mechanisms are poorly understood. One potential mechanism is hyperexcitability
of spinal neurons (ie, central sensitization). Given that Native Americans (NAs) are
more likely to have ALEs and to have a higher prevalence of chronic pain, the relationship
between ALEs and spinal hyperexcitability might contribute to their pain risk. The
present study assessed temporal summation of the nociceptive flexion reflex (TS-NFR;
a correlate of spinal hyperexcitability) and pain (TS-Pain) in 246 healthy, pain-free
non-Hispanic whites and NAs. The Life Events Checklist was used to assess the number
of ALEs. Multilevel growth models were used to predict TS-NFR and TS-Pain, after controlling
for age, perceived stress, psychological problems, negative and positive affect, and
painful stimulus intensity. ALEs and negative affect were significantly associated
with greater pain, but not enhanced TS-Pain. By contrast, ALEs were associated with
enhanced TS-NFR. Race did not moderate these relationships. This finding implies that
ALEs promote hyperalgesia as a result of increased spinal neuron excitability. Although
relationships between ALEs and the nociceptive flexion reflex/pain were not stronger
in NAs, given prior evidence that NAs experience more ALEs, this factor might contribute
to the higher prevalence of chronic pain in NAs.
Perspective
This study found a dose-dependent relationship between ALEs and spinal neuron excitability.
Although the relationship was not stronger in NAs than non-Hispanic whites, given
prior evidence that NAs experience more ALEs, this could contribute to the higher
prevalence of chronic pain in NAs.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to The Journal of PainAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Population attributable fractions of psychiatric disorders and suicide ideation and attempts associated with adverse childhood experiences.Am J Public Health. 2008; 98: 946-952
- Adverse childhood experiences and prescribed psychotropic medications in adults.Am J Prev Med. 2007; 32: 389-394
- The enduring effects of abuse and related adverse experiences in childhood.Eur Arch Psychiatry Clin Neurosci. 2006; 256: 174-186
- Adverse childhood experiences, alcoholic parents, and later risk of alcoholism and depression.Psychiatr Serv. 2002; 53: 1001-1009
- Electrophysiological and psychophysical quantification of temporal summation in the human nociceptive system.Eur J Appl Physiol. 1994; 68: 266-273
- The effect of N-methyl-D-aspartate antagonist (ketamine) on single and repeated nociceptive stimuli: A placebo-controlled experimental human study.Anesth Analg. 1995; 81: 63
- Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia.Pain. 2004; 107: 7-15
- Associations among county-level social determinants of health, child maltreatment, and emotional support on health-related quality of life in adulthood.Psychol Violence. 2015; 5: 183
- Prevalence of DSM-IV disorders and attendant help-seeking in 2 American Indian reservation populations.Arch Gen Psychiatry. 2005; 62: 99-108
- Prevalence of mental disorders and utilization of mental health services in two American Indian reservation populations: Mental health disparities in a national context.Am J Psychiatry. 2005; 162: 1723-1732
- The psychosis screening questionnaire.Int J Methods Psychiatr Res. 1995; 5: 11-19
- Chronic pain and PTSD: Evolving views on their comorbidity.Perspect Psychiatr Care. 2015; 51: 295-304
- Relationship between post-traumatic stress disorder and pain in two American Indian tribes.Pain Med. 2005; 6: 72-79
- Cognitive and emotional control of pain and its disruption in chronic pain.Nat Rev Neurosci. 2013; 14: 502-511
- Transition from acute to chronic pain and disability: A model including cognitive, affective, and trauma factors.Pain. 2008; 134: 69-79
- Adverse childhood experiences and sleep disturbances in adults.Sleep Med. 2011; 12: 773-779
- Adverse childhood experiences and the risk of depressive disorders in adulthood.J Affect Disord. 2004; 82: 217-225
- Health-related quality of life among adults who experienced maltreatment during childhood.Am J Public Health. 2008; 98: 1094-1100
- Emotional modulation of pain and spinal nociception in persons with severe insomnia symptoms.Ann Behav Med. 2014; 47: 303-315
- SCL-90-R: Symptom Checklist-90-R: Administration, Scoring & Procedures Manual.National Computer Systems, Inc., Minneapolis, MN1994
- Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: The adverse childhood experiences study.Pediatrics. 2003; 111: 564-572
- Catastrophizing predicts changes in thermal pain responses after resolution of acute dental pain.J Pain. 2004; 5: 164-170
- It's ok to ask about past abuse.An Psychol. 2007; 62: 327-328
- Relationship between multiple forms of childhood maltreatment and adult mental health in community respondents: Results from the adverse childhood experiences study.Am J Psychiatr. 2003; 160: 1453-1460
- Wind-up and the NMDA receptor complex from a clinical perspective.Eur J Pain. 2000; 4: 5-15
- 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
- Central nervous system mechanisms of pain modulation.in: McMahon SB Koltzenburg M Textbook of Pain. 5th ed. Elsevier/Churchill Livingstone, Philadelphia2006: 125-143
- Is self-reported childhood abuse history associated with pain perception among healthy young women and men?.Clin J Pain. 2005; 21: 387-397
- Catastrophizing is related to pain ratings, but not nociceptive flexion reflex threshold.Pain. 2002; 99: 459-463
- Laboratory pain perception and clinical pain in post-menopausal women and age-matched men with osteoarthritis: Relationship to pain coping and hormonal status.Pain. 2004; 112: 274-281
- Using normalized EMG to define the Nociceptive Flexion Reflex (NFR) threshold: Further evaluation of standardized scoring criteria.Pain. 2009; 145: 211-218
- Sex and pain-related psychological variables are associated with thermal pain sensitivity for patients with chronic low back pain.J Pain. 2007; 8: 2-10
- Stress sensitivity mediates the relationship between traumatic life events and attenuated positive psychotic symptoms differentially by gender in a college population sample.J Psychiatr Res. 2014; 53: 111-118
- Contact heat-evoked temporal summation: Tonic versus repetitive-phasic stimulation.Pain. 2006; 122: 295-305
- Psychometric properties of the life events checklist.Assessment. 2004; 11: 330-341
- The effects of ketamine on the temporal summation (wind-up) of the R(III) nociceptive flexion reflex and pain in humans.Anesth Analg. 2000; 90: 408-414
- 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).in: Presented at the American Pain Society meeting, Milwaukee, WI2019
- Childhood adversities in patients with fibromyalgia and somatoform pain disorder.Eur J Pain. 2003; 7: 113-119
- 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
- Adverse childhood exposures and alcohol dependence among seven Native American tribes.Am J Prev Med. 2003; 25: 238-244
- Psychological treatments for irritable bowel syndrome: A systematic review and meta-analysis.J Consult Clin Psychol. 2004; 72: 1100
- Childhood physical and sexual abuse and subsequent depressive and anxiety disorders for two American Indian tribes.Psychol Med. 2005; 35: 329-340
- Racial and ethnic disparities in preterm birth: The role of stressful life events.Am J Obstet Gynecol. 2004; 191: 691-699
- Pain and emotion: A biopsychosocial review of recent research.J Clin Psychol. 2011; 67: 942-968
- Somatoform dissociation and adverse childhood experiences in the general population.J Nerv Ment Dis. 2004; 192: 337-342
- Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain: Evidence for altered temporal summation of pain.Pain. 1998; 76: 71-81
- Social epidemiology of trauma among 2 American Indian reservation populations.Am J Public Health. 2005; 95: 851-859
Martin SL, Kerr KL, Bartley EJ, Kuhn BL, Palit S, Terry EL, DelVentura JL, Rhudy JL: Respiration-induced hypoalgesia: Exploration of potential mechanisms. J Pain 13:755-763, 212
- The association between tender points, psychological distress, and adverse childhood experiences: A community‐based study.Arthritis Rheum. 1999; 42: 1397-1404
- Pain and emotion: Effects of affective picture modulation.Psychosom Med. 2001; 63: 79-90
- Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres.Nature. 1965; 206: 97
- Evidence for acute central sensitization to prolonged experimental pain in posttraumatic stress disorder.Pain Med. 2014; 15: 762-771
- Cumulative burden of lifetime adversities: Trauma and mental health in low-SES African Americans and Latino/as.Psychol Trauma. 2015; 7: 243
- N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists block the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat's knee joint.J Neurophysiol. 1993; 70: 1365
- Does altered pain sensitivity contribute to pain risk in Native Americans? Preliminary findings from the Oklahoma Study of Native American Pain Risk (OKSNAP) [abstract].in: Paper presented at the 17th IAPS World Congress on Pain 2018 meeting, Boston, MASeptember 2018
- Examining emotional modulation of pain and spinal nociception in Native Americans: A preliminary investigation.Int J Psychophysiol. 2013; 90: 272-281
- Exploring pain processing differences in Native Americans.Health Psychol. 2013; 32: 1127-1136
- Post‐traumatic stress disorder in episodic and chronic migraine.Headache. 2008; 48: 517-522
- Cerebral and cerebrospinal processes underlying counterirritation analgesia.J Neurosci. 2009; 29: 14236-14246
- Posttraumatic stress disorder among ethnoracial minorities in the United States.Clin Psychol. 2008; 15: 35-61
- A quantitative review of ethnic group differences in experimental pain response: Do biology, psychology, and culture matter?.Pain Med. 2012; 13: 522-540
- Habituation, sensitization, and emotional valence modulation of pain responses.Pain. 2010; 148: 320-327
- Defining the nociceptive flexion reflex (NFR) threshold in human participants: A comparison of different scoring criteria.Pain. 2007; 128: 244-253
- Sensory, Affective, and Catastrophizing Reactions to Multiple Stimulus Modalities: Results from the Oklahoma Study of Native American Pain Risk (OK-SNAP).J Pain. 2019; 20: 965-979
- Using multilevel growth curve modeling to examine emotional modulation of temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR).Pain. 2012; 153: 2274-2282
- Pain catastrophizing is related to temporal summation of pain, but not temporal summation of the nociceptive flexion reflex.Pain. 2011; 152: 794-801
- Does in-vivo catastrophizing engage descending modulation of spinal nociception?.J Pain. 2007; 8: 325-333
- Fear and anxiety: Divergent effects on human pain thresholds.Pain. 2000; 84: 65-75
- The role of emotion in pain modulation.Curr Opin Psychiatry. 2001; 14: 241-245
- Emotional modulation of spinal nociception and pain: The impact of predictable noxious stimulation.Pain. 2006; 126: 221-233
- Emotional control of nociceptive reactions (ECON): Do affective valence and arousal play a role?.Pain. 2008; 136: 250-261
- Racial/ethnic differences in the experience of chronic pain.Pain. 2002; 100: 291
- Prevalence and characteristics of trauma and posttraumatic stress disorder in a southwestern American Indian community.Am J Psychiatry. 1997; 154: 1582-1588
- Prevalence, characteristics, and impact of childhood sexual abuse in a Southwestern American Indian tribe.Child Abuse Negl. 1997; 21: 769-787
- Cerebral and spinal modulation of pain by emotions.Proc Natl Acad Sci U S A. 2009; 106: 20900-20905
- A review of childhood abuse, health, and pain-related problems: The role of psychiatric disorders and current life stress.J Trauma Dissociation. 2009; 10: 170-188
- A brief cognitive-behavioural intervention for pain reduces secondary hyperalgesia.Pain. 2014; 155: 1446-1452
Sandkühler J: Spinal cord plasticity and pain. In: McMahon SB, Koltzenburg M, Tracey I, Turk DC, (eds). Wall and Melzack's textbook of pain 6th ed. Vol 6. Philadelphia, PA, Elsevier, 2013, pp 94-110
- The lower limb flexion reflex in humans.Prog Neurobiol. 2005; 77: 353-395
- Heightened temporal summation of pain in patients with functional gastrointestinal disorders and history of trauma.Ann Behav Med. 2015; 49: 785-792
- Sensitivity to pain (with an analysis of 450 cases).Can Med Assoc J. 1943; 48: 437
- State-Trait Anxiety Inventory.Consulting Psychologists Press, Palo-Alto, CA1983
- The Pain Catastrophizing Scale: Development and validation.Psychol Assess. 1995; 7: 524-532
- Mental health problems and post‐migration stress among multi‐traumatized refugees attending outpatient clinics upon resettlement to Norway.Scand J Psychol. 2012; 53: 316-332
- Emotional modulation of pain and spinal nociception in persons with major depressive disorder (MDD).Pain. 2013; 154: 2759-2768
- Standardizing procedures to study sensitization of human spinal nociceptive processes: Comparing parameters for temporal summation of the nociceptive flexion reflex (TS-NFR).Int J Psychophysiol. 2011; 81: 263-274
- Experimental reduction of pain catastrophizing modulates pain report but not spinal nociception as verified by mediation analyses.Pain. 2015; 156: 1477-1488
- Does pain catastrophizing contribute to threat-evoked amplification of pain and spinal nociception?.Pain. 2016; 157: 456-465
- Psychological pain treatment in fibromyalgia syndrome: Efficacy of operant behavioural and cognitive behavioural treatments.Arthrit Res Ther. 2006; 8: R121
- Cocaine‐related attentional bias following trauma cue exposure among cocaine dependent in‐patients with and without post‐traumatic stress disorder.Addiction. 2011; 106: 1810-1818
- Modulation of spinal excitability: Co-operation between neurokinin and excitatory amino acid neurotransmitters.Trends Neurosci. 1994; 17: 432-438
- SF-36 Health Survey Manual and Interpretation Guide.The Health Institute New England Medical Center, Boston, MA1993
- Development and validation of brief measures of positive and negative affect: The PANAS scales.J Pers Soc Psychol. 1988; 54: 1063
- The preeminence of early life trauma as a risk factor for worsened long-term health outcomes in women.Curr Psychiatr Rep. 2015; 17
- The influence of negative emotions on pain: Behavioral effects and neural mechanisms.Neuroimage. 2009; 47: 987-994
- Understanding and applying basic statistical methods using R.John Wiley & Sons, New York, NY2016
- Windup and central sensitization are not equivalent.Pain. 1996; 66: 105-108
- Central sensitization: Implications for the diagnosis and treatment of pain.Pain. 2011; 152: S2-S15
- 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
- Pain modulation profile and pain therapy: Between pro- and antinociception.Pain. 2014; 155: 663-665
- Excitatory amino acid receptors involved in primary afferent-evoked polysynaptic EPSPs of substantia gelatinosa neurons in the adult rat spinal cord slice.Neurosci Lett. 1992; 143: 131-134
- The Impact of Adverse Childhood Events on Temporal Summation of Second Pain.Texas A & M University, College Station, TX2012
- Simultaneous recordings of wind-up of paired spinal dorsal horn nociceptive neuron and nociceptive flexion reflex in rats.Brain Res. 2003; 960: 235-245
- Electrophysiological characterization of facilitated spinal withdrawal reflex to repetitive electrical stimuli and its modulation by central glutamate receptor in spinal anesthetized rats.Brain Res. 2004; 1009: 110-119
Article Info
Publication History
Published online: February 15, 2019
Accepted:
February 11,
2019
Received in revised form:
February 11,
2019
Received:
August 7,
2018
Footnotes
Research reported was supported by the National Institute On Minority Health and Health Disparities of the National Institute of Health under Award Number R01MD007807. Edward Lannon, Shreela Palit, and Yvette Güereca were supported by a National Science Foundation Graduate Research Fellowship Program. 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.
The authors have no conflicts of interest to declare.
Identification
Copyright
© 2019 by the American Pain Society
