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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

Published:February 15, 2019DOI:https://doi.org/10.1016/j.jpain.2019.02.006

      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

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      References

        • Afifi TO
        • Enns MW
        • Cox BJ
        • Asmundson GJ
        • Stein MB
        • Sareen J
        Population attributable fractions of psychiatric disorders and suicide ideation and attempts associated with adverse childhood experiences.
        Am J Public Health. 2008; 98: 946-952
        • Anda RF
        • Brown DW
        • Felitti VJ
        • Bremner JD
        • Dube SR
        • Giles WH
        Adverse childhood experiences and prescribed psychotropic medications in adults.
        Am J Prev Med. 2007; 32: 389-394
        • 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
        • Anda RF
        • Whitfield CL
        • Felitti VJ
        • Chapman D
        • Edwards VJ
        • Dube SR
        • Williamson DF
        Adverse childhood experiences, alcoholic parents, and later risk of alcoholism and depression.
        Psychiatr Serv. 2002; 53: 1001-1009
        • Arendt-Nielsen L
        • Brennum J
        • Sindrup S
        • Bak P
        Electrophysiological and psychophysical quantification of temporal summation in the human nociceptive system.
        Eur J Appl Physiol. 1994; 68: 266-273
        • Arendt-Nielsen L
        • Petersen-Felix S
        • Fischer M
        • Bak P
        • Bjerring P
        • Zbinden AM
        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
        • Banic B
        • Petersen-Felix S
        • Andersen OK
        • Radanov BP
        • Villiger PM
        • Arendt-Nielsen L
        • Curatolo M
        Evidence for spinal cord hypersensitivity in chronic pain after whiplash injury and in fibromyalgia.
        Pain. 2004; 107: 7-15
        • Barile JP
        • Edwards VJ
        • Dhingra SS
        • Thompson WW
        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
        • Beals J
        • Manson SM
        • Whitesell NR
        • Spicer P
        • Novins DK
        • Mitchell CM
        Prevalence of DSM-IV disorders and attendant help-seeking in 2 American Indian reservation populations.
        Arch Gen Psychiatry. 2005; 62: 99-108
        • Beals J
        • Novins DK
        • Whitesell NR
        • Spicer P
        • Mitchell CM
        • Manson SM
        • American Indian Service Utilization PE, Risk, Team PFP
        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
        • Bebbington P
        • Nayani T
        The psychosis screening questionnaire.
        Int J Methods Psychiatr Res. 1995; 5: 11-19
        • Brennstuhl MJ
        • Tarquinio C
        • Montel S
        Chronic pain and PTSD: Evolving views on their comorbidity.
        Perspect Psychiatr Care. 2015; 51: 295-304
        • Buchwald D
        • Goldberg J
        • Noonan C
        • Beals J
        • Manson S
        Relationship between post-traumatic stress disorder and pain in two American Indian tribes.
        Pain Med. 2005; 6: 72-79
        • Bushnell MC
        • Ceko M
        • Low LA
        Cognitive and emotional control of pain and its disruption in chronic pain.
        Nat Rev Neurosci. 2013; 14: 502-511
        • Casey CY
        • Greenberg MA
        • Nicassio PM
        • Harpin RE
        • Hubbard D
        Transition from acute to chronic pain and disability: A model including cognitive, affective, and trauma factors.
        Pain. 2008; 134: 69-79
        • Chapman DP
        • Wheaton AG
        • Anda RF
        • Croft JB
        • Edwards VJ
        • Liu Y
        • Sturgis SL
        • Perry GS
        Adverse childhood experiences and sleep disturbances in adults.
        Sleep Med. 2011; 12: 773-779
        • Chapman DP
        • Whitfield CL
        • Felitti VJ
        • Dube SR
        • Edwards VJ
        • Anda RF
        Adverse childhood experiences and the risk of depressive disorders in adulthood.
        J Affect Disord. 2004; 82: 217-225
        • Corso PS
        • Edwards VJ
        • Fang X
        • Mercy JA
        Health-related quality of life among adults who experienced maltreatment during childhood.
        Am J Public Health. 2008; 98: 1094-1100
        • DelVentura JL
        • Terry EL
        • Bartley EJ
        • Rhudy JL
        Emotional modulation of pain and spinal nociception in persons with severe insomnia symptoms.
        Ann Behav Med. 2014; 47: 303-315
        • Derogatis LR
        SCL-90-R: Symptom Checklist-90-R: Administration, Scoring & Procedures Manual.
        National Computer Systems, Inc., Minneapolis, MN1994
        • Dube SR
        • Felitti VJ
        • Dong M
        • Chapman DP
        • Giles WH
        • Anda RF
        Childhood abuse, neglect, and household dysfunction and the risk of illicit drug use: The adverse childhood experiences study.
        Pediatrics. 2003; 111: 564-572
        • Edwards RR
        • Fillingim RB
        • Maixner W
        • Sigurdsson A
        • Haythornthwaite J
        Catastrophizing predicts changes in thermal pain responses after resolution of acute dental pain.
        J Pain. 2004; 5: 164-170
        • Edwards VJ
        • Dube SR
        • Felitti VJ
        • Anda RF
        It's ok to ask about past abuse.
        An Psychol. 2007; 62: 327-328
        • Edwards VJ
        • Holden GW
        • Felitti VJ
        • Anda RF
        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
        • Eide PK
        Wind-up and the NMDA receptor complex from a clinical perspective.
        Eur J Pain. 2000; 4: 5-15
        • 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
        • Fields HL
        • Basbaum AI
        • Heinricher MM
        Central nervous system mechanisms of pain modulation.
        in: McMahon SB Koltzenburg M Textbook of Pain. 5th ed. Elsevier/Churchill Livingstone, Philadelphia2006: 125-143
        • Fillingim RB
        • Edwards RR
        Is self-reported childhood abuse history associated with pain perception among healthy young women and men?.
        Clin J Pain. 2005; 21: 387-397
        • France CR
        • France JL
        • al'Absi M
        • Ring C
        • McIntyre D
        Catastrophizing is related to pain ratings, but not nociceptive flexion reflex threshold.
        Pain. 2002; 99: 459-463
        • France CR
        • Keefe FJ
        • Emery CF
        • Affleck G
        • France JL
        • Waters S
        • Caldwell DS
        • Stainbrook D
        • Hackshaw KV
        • Edwards C
        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
        • France CR
        • Rhudy JL
        • McGlone S
        Using normalized EMG to define the Nociceptive Flexion Reflex (NFR) threshold: Further evaluation of standardized scoring criteria.
        Pain. 2009; 145: 211-218
        • George SZ
        • Wittmer VT
        • Fillingim RB
        • Robinson ME
        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
        • Gibson LE
        • Anglin DM
        • Klugman JT
        • Reeves LE
        • Fineberg AM
        • Maxwell SD
        • Kerns CM
        • Ellman LM
        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
        • Granot M
        • Granovsky Y
        • Sprecher E
        • Nir RR
        • Yarnitsky D
        Contact heat-evoked temporal summation: Tonic versus repetitive-phasic stimulation.
        Pain. 2006; 122: 295-305
        • Gray MJ
        • Litz BT
        • Hsu JL
        • Lombardo TW
        Psychometric properties of the life events checklist.
        Assessment. 2004; 11: 330-341
        • Guirimand F
        • Dupont X
        • Brasseur L
        • Chauvin M
        • Bouhassira D
        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
        • Huber FA
        • Kuhn BL
        • Lannon EW
        • Sturycz CA
        • Payne MF
        • Hellman N
        • Toledo TA
        • Guereca YM
        • DeMuth M
        • Palit S
        • Shadlow JO
        • Rhudy JL
        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
        • Imbierowicz K
        • Egle UT
        Childhood adversities in patients with fibromyalgia and somatoform pain disorder.
        Eur J Pain. 2003; 7: 113-119
        • 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
        • Koss MP
        • Yuan NP
        • Dightman D
        • Prince RJ
        • Polacca M
        • Sanderson B
        • Goldman D
        Adverse childhood exposures and alcohol dependence among seven Native American tribes.
        Am J Prev Med. 2003; 25: 238-244
        • Lackner JM
        • Mesmer C
        • Morley S
        • Dowzer C
        • Hamilton S
        Psychological treatments for irritable bowel syndrome: A systematic review and meta-analysis.
        J Consult Clin Psychol. 2004; 72: 1100
        • Libby AM
        • Orton HD
        • Novins DK
        • Beals J
        • Manson SM
        Childhood physical and sexual abuse and subsequent depressive and anxiety disorders for two American Indian tribes.
        Psychol Med. 2005; 35: 329-340
        • Lu MC
        • Chen B
        Racial and ethnic disparities in preterm birth: The role of stressful life events.
        Am J Obstet Gynecol. 2004; 191: 691-699
        • Lumley MA
        • Cohen JL
        • Borszcz GS
        • Cano A
        • Radcliffe AM
        • Porter LS
        • Schubiner H
        • Keefe FJ
        Pain and emotion: A biopsychosocial review of recent research.
        J Clin Psychol. 2011; 67: 942-968
        • Maaranen P
        • Tanskanen A
        • Haatainen K
        • Koivumaa-Honkanen H
        • Hintikka J
        • Viinamäki H
        Somatoform dissociation and adverse childhood experiences in the general population.
        J Nerv Ment Dis. 2004; 192: 337-342
        • Maixner W
        • Fillingim R
        • Sigurdsson A
        • Kincaid S
        • Silva S
        Sensitivity of patients with painful temporomandibular disorders to experimentally evoked pain: Evidence for altered temporal summation of pain.
        Pain. 1998; 76: 71-81
        • Manson SM
        • Beals J
        • Klein SA
        • Croy CD
        • Team A-s
        Social epidemiology of trauma among 2 American Indian reservation populations.
        Am J Public Health. 2005; 95: 851-859
      1. 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

        • McBeth J
        • Macfarlane GJ
        • Benjamin S
        • Morris S
        • Silman AJ
        The association between tender points, psychological distress, and adverse childhood experiences: A community‐based study.
        Arthritis Rheum. 1999; 42: 1397-1404
        • Meagher MW
        • Arnau RC
        • Rhudy JL
        Pain and emotion: Effects of affective picture modulation.
        Psychosom Med. 2001; 63: 79-90
        • Mendell LM
        • Wall PD
        Responses of single dorsal cord cells to peripheral cutaneous unmyelinated fibres.
        Nature. 1965; 206: 97
        • Moeller-Bertram T
        • Strigo IA
        • Simmons AN
        • Schilling JM
        • Patel P
        • Baker DG
        Evidence for acute central sensitization to prolonged experimental pain in posttraumatic stress disorder.
        Pain Med. 2014; 15: 762-771
        • Myers HF
        • Wyatt GE
        • Ullman JB
        • Loeb TB
        • Chin D
        • Prause N
        • Zhang M
        • Williams JK
        • Slavich GM
        • Liu H
        Cumulative burden of lifetime adversities: Trauma and mental health in low-SES African Americans and Latino/as.
        Psychol Trauma. 2015; 7: 243
        • Neugebauer V
        • Lucke T
        • Schaible HG
        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
        • Newsom GC
        • Toledo TA
        • Kuhn BL
        • Sturycz CA
        • Lannon EW
        • Palit S
        • Güereca YM
        • Payne MF
        • Hellman N
        • Shadlow JO
        • Rhudy JL
        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
        • Palit S
        • Kerr KL
        • Kuhn BL
        • DelVentura JL
        • Terry EL
        • Bartley EJ
        • Shadlow JO
        • Rhudy JL
        Examining emotional modulation of pain and spinal nociception in Native Americans: A preliminary investigation.
        Int J Psychophysiol. 2013; 90: 272-281
        • Palit S
        • Kerr KL
        • Kuhn BL
        • Terry EL
        • DelVentura JL
        • Bartley EJ
        • Shadlow JO
        • Rhudy JL
        Exploring pain processing differences in Native Americans.
        Health Psychol. 2013; 32: 1127-1136
        • Peterlin BL
        • Tietjen G
        • Meng S
        • Lidicker J
        • Bigal M
        Post‐traumatic stress disorder in episodic and chronic migraine.
        Headache. 2008; 48: 517-522
        • Piché M
        • Arsenault M
        • Rainville P
        Cerebral and cerebrospinal processes underlying counterirritation analgesia.
        J Neurosci. 2009; 29: 14236-14246
        • Pole N
        • Gone JP
        • Kulkarni M
        Posttraumatic stress disorder among ethnoracial minorities in the United States.
        Clin Psychol. 2008; 15: 35-61
        • Rahim-Williams B
        • Riley III, JL
        • Williams AK
        • Fillingim RB
        A quantitative review of ethnic group differences in experimental pain response: Do biology, psychology, and culture matter?.
        Pain Med. 2012; 13: 522-540
        • Rhudy JL
        • Bartley EJ
        • Williams AE
        Habituation, sensitization, and emotional valence modulation of pain responses.
        Pain. 2010; 148: 320-327
        • 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
        • Lannon EW
        • Kuhn BL
        • Palit S
        • Payne MF
        • Sturycz CA
        • Hellman N
        • Güereca YM
        • Toledo TA
        • Coleman HB
        • Thompson KA
        • Fisher JM
        • Herbig SP
        • Barnoski KB
        • Chee L
        • Shadlow JO
        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
        • Rhudy JL
        • Martin SL
        • Terry EL
        • DelVentura JL
        • Kerr KL
        • Palit S
        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
        • Rhudy JL
        • Martin SL
        • Terry EL
        • France CR
        • Bartley EJ
        • DelVentura JL
        • Kerr KL
        Pain catastrophizing is related to temporal summation of pain, but not temporal summation of the nociceptive flexion reflex.
        Pain. 2011; 152: 794-801
        • Rhudy JL
        • Maynard LJ
        • Russell JL
        Does in-vivo catastrophizing engage descending modulation of spinal nociception?.
        J Pain. 2007; 8: 325-333
        • Rhudy JL
        • Meagher MW
        Fear and anxiety: Divergent effects on human pain thresholds.
        Pain. 2000; 84: 65-75
        • Rhudy JL
        • Meagher MW
        The role of emotion in pain modulation.
        Curr Opin Psychiatry. 2001; 14: 241-245
        • Rhudy JL
        • Williams AE
        • McCabe KM
        • Rambo PL
        • Russell JL
        Emotional modulation of spinal nociception and pain: The impact of predictable noxious stimulation.
        Pain. 2006; 126: 221-233
        • Rhudy JL
        • Williams AE
        • McCabe KM
        • Russell JL
        • Maynard LJ
        Emotional control of nociceptive reactions (ECON): Do affective valence and arousal play a role?.
        Pain. 2008; 136: 250-261
        • Riley III, JL
        • Wade JB
        • Myers CD
        • Sheffield D
        • Papas RK
        • Price DD
        Racial/ethnic differences in the experience of chronic pain.
        Pain. 2002; 100: 291
        • Robin RW
        • Chester B
        • Rasmussen JK
        • Jaranson JM
        • Goldman D
        Prevalence and characteristics of trauma and posttraumatic stress disorder in a southwestern American Indian community.
        Am J Psychiatry. 1997; 154: 1582-1588
        • Robin RW
        • Chester B
        • Rasmussen JK
        • Jaranson JM
        • Goldman D
        Prevalence, characteristics, and impact of childhood sexual abuse in a Southwestern American Indian tribe.
        Child Abuse Negl. 1997; 21: 769-787
        • Roy M
        • Piche M
        • Chen J-I
        • Peretz I
        • Rainville P
        Cerebral and spinal modulation of pain by emotions.
        Proc Natl Acad Sci U S A. 2009; 106: 20900-20905
        • Sachs-Ericsson N
        • Cromer K
        • Hernandez A
        • Kendall-Tackett K
        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
        • Salomons TV
        • Moayedi M
        • Erpelding N
        • Davis KD
        A brief cognitive-behavioural intervention for pain reduces secondary hyperalgesia.
        Pain. 2014; 155: 1446-1452
      2. 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

        • Sandrini G
        • Serrao M
        • Rossi P
        • Romaniello A
        • Cruccu G
        • Willer JC
        The lower limb flexion reflex in humans.
        Prog Neurobiol. 2005; 77: 353-395
        • Sherman AL
        • Morris MC
        • Bruehl S
        • Westbrook TD
        • Walker LS
        Heightened temporal summation of pain in patients with functional gastrointestinal disorders and history of trauma.
        Ann Behav Med. 2015; 49: 785-792
        • Sherman ED
        Sensitivity to pain (with an analysis of 450 cases).
        Can Med Assoc J. 1943; 48: 437
        • Spielberger CD
        State-Trait Anxiety Inventory.
        Consulting Psychologists Press, Palo-Alto, CA1983
        • Sullivan MJL
        • Bishop SR
        • Pivik J
        The Pain Catastrophizing Scale: Development and validation.
        Psychol Assess. 1995; 7: 524-532
        • Teodorescu DS
        • Heir T
        • Hauff E
        • Wentzel‐Larsen T
        • Lien L
        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
        • Terry EL
        • DelVentura JL
        • Bartley EJ
        • Vincent A
        • Rhudy JL
        Emotional modulation of pain and spinal nociception in persons with major depressive disorder (MDD).
        Pain. 2013; 154: 2759-2768
        • Terry EL
        • France CR
        • Bartley EJ
        • DelVentura JL
        • Kerr KL
        • Vincent AL
        • Rhudy JL
        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
        • Terry EL
        • Thompson KA
        • Rhudy JL
        Experimental reduction of pain catastrophizing modulates pain report but not spinal nociception as verified by mediation analyses.
        Pain. 2015; 156: 1477-1488
        • Terry EL
        • Thompson KA
        • Rhudy JL
        Does pain catastrophizing contribute to threat-evoked amplification of pain and spinal nociception?.
        Pain. 2016; 157: 456-465
        • Thieme K
        • Flor H
        • Turk DC
        Psychological pain treatment in fibromyalgia syndrome: Efficacy of operant behavioural and cognitive behavioural treatments.
        Arthrit Res Ther. 2006; 8: R121
        • Tull MT
        • McDermott MJ
        • Gratz KL
        • Coffey SF
        • Lejuez CW
        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
        • Urban L
        • Thompson SW
        • Dray A
        Modulation of spinal excitability: Co-operation between neurokinin and excitatory amino acid neurotransmitters.
        Trends Neurosci. 1994; 17: 432-438
        • Ware JE
        • Snow KK
        • Kosinski M
        • Gandek B
        SF-36 Health Survey Manual and Interpretation Guide.
        The Health Institute New England Medical Center, Boston, MA1993
        • Watson D
        • Clark LA
        • Tellegen A
        Development and validation of brief measures of positive and negative affect: The PANAS scales.
        J Pers Soc Psychol. 1988; 54: 1063
        • Westfall NC
        • Nemeroff CB
        The preeminence of early life trauma as a risk factor for worsened long-term health outcomes in women.
        Curr Psychiatr Rep. 2015; 17
        • Wiech K
        • Tracey I
        The influence of negative emotions on pain: Behavioral effects and neural mechanisms.
        Neuroimage. 2009; 47: 987-994
        • Wilcox RR
        Understanding and applying basic statistical methods using R.
        John Wiley & Sons, New York, NY2016
        • Woolf CJ
        Windup and central sensitization are not equivalent.
        Pain. 1996; 66: 105-108
        • Woolf CJ
        Central sensitization: Implications for the diagnosis and treatment of pain.
        Pain. 2011; 152: S2-S15
        • 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
        • Yarnitsky D
        • Granot M
        • Granovsky Y
        Pain modulation profile and pain therapy: Between pro- and antinociception.
        Pain. 2014; 155: 663-665
        • Yoshimura M
        • Nishi S
        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
        • You DS
        The Impact of Adverse Childhood Events on Temporal Summation of Second Pain.
        Texas A & M University, College Station, TX2012
        • You HJ
        • Dahl Morch C
        • Chen J
        • Arendt-Nielsen L
        Simultaneous recordings of wind-up of paired spinal dorsal horn nociceptive neuron and nociceptive flexion reflex in rats.
        Brain Res. 2003; 960: 235-245
        • You HJ
        • Morch CD
        • Arendt-Nielsen L
        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

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