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Native Americans (NAs) have higher pain rates than the general U.S. population. It has been found that increased central sensitization and reduced pain inhibition are pronociceptive processes that increase pain risk; yet, little attention has focused on the influence of psychosocial factors. Discrimination is a psychosocial factor associated with increased pain in other minoritized groups; however, it is unclear whether it also promotes pain in NAs. This study analyzed data from 269 healthy, pain-free participants (N = 134 non-Hispanic whites [NHWs], N = 135 NAs) from the Oklahoma Study of Native American Pain Risk. Experienced discrimination was measured using the Everyday Discrimination Scale (EDS). Nociceptive processes were measured via static measures of spinal sensitivity (nociceptive flexion reflex [NFR] threshold, 3-stimulation NFR threshold), temporal summation of pain (TS-Pain) and nociceptive flexion reflex (TS-NFR), and conditioned pain modulation of pain (CPM-Pain) and NFR (CPM-NFR). Results demonstrated that greater discrimination was associated with enhanced TS-NFR and impaired CPM-NFR but not static measures of spinal sensitivity or measures of pain modulation (TS-Pain, CPM-Pain). Although the effects of discrimination on outcomes were similar in both groups (not moderated by ethnicity), NAs experienced higher levels of discrimination and therefore discrimination mediated a relationship between ethnicity and impaired CPM-NFR. This indicates experienced discrimination may promote a pain risk phenotype in NAs that involves spinal sensitization resulting from impaired inhibition of spinal nociception without sensitization of pain experience. PERSPECTIVE: This study found that discrimination was associated with spinal sensitization and impaired descending inhibition of spinal nociception. These findings bolster our understanding of how social stressors experienced disproportionately by minoritized groups can contribute to pain outcomes.

The nociceptive flexion reflex (NFR) is a spinally mediated withdrawal response and is used as an electrophysiological marker of descending modulation of spinal nociception. Chemical and pharmacological modulation of nociceptive neurotransmission at the spinal level has been evidenced by direct effects of neurotransmitters and pharmacological agents on the NFR. Largely unexplored are, however, the effects of nonpharmacological noninvasive conservative interventions on the NFR. Therefore, a systematic review and meta-analysis was performed and reported following the PRISMA guidelines to determine whether and to what extent spinal nociception measured through the assessment of the NFR is modulated by conservative therapy in patients and healthy individuals. Five electronic databases were searched to identify relevant articles. Retrieved articles were screened on eligibility using the predefined inclusion criteria. Risk of bias was investigated according to Version 2 of the Cochrane risk-of-bias assessment tool for randomized trials. The evidence synthesis for this review was conducted in accordance with the Grading of Recommendations Assessment, Development and Evaluation. Thirty-six articles were included. Meta-analyses provided low-quality evidence showing that conservative therapy decreases NFR area and NFR magnitude and moderate-quality evidence for increases in NFR latency. This suggests that conservative interventions can exert immediate central effects by activating descending inhibitory pathways to reduce spinal nociception. Such interventions may help prevent and treat chronic pain characterized by enhanced spinal nociception. Furthermore, given the responsiveness of the NFR to conservative interventions, the NFR assessment seems to be an appropriate tool in empirical evaluations of treatment strategies.PROSPERO registration number: CRD42020164495.

Chronic pain results in considerable suffering, as well as significant economic and societal costs. Previous evidence suggests that Native Americans (NAs) have higher rates of chronic pain than other U.S. racial or ethnic groups, but the mechanisms contributing to this pain disparity are poorly understood. The Oklahoma Study of Native American Pain Risk was developed to address this issue and recruited healthy, pain-free NAs and non-Hispanic Whites. Cross-sectional analyses identified several measures of adversity (eg, trauma and discrimination), cognitive-affective factors (perceived stress and pain-related anxiety/catastrophizing), and cardiometabolic factors (eg, body mass index, blood pressure, and heart rate variability) that were associated with pronociceptive processes (eg, central sensitization, descending inhibition, and hyperalgesia). Every 6-months after enrollment, eligible participants (N = 277) were recontacted and assessed for the onset of chronic pain. This study examines predictors of chronic pain onset in the 222 participants (80%) who responded over the first 2 years. The results show that NAs developed chronic pain at a higher rate than non-Hispanic Whites (OR = 2.902, P0.05), even after controlling for age, sex, income, and education. Moreover, serial mediation models identified several potential pathways to chronic pain onset within the NA group. These paths included perceived discrimination, psychological stress, pain-related anxiety, a composite measure of cardiometabolic risk, and impaired descending inhibition of spinal nociception (assessed from conditioned pain modulation of the nociceptive flexion reflex). These results provide the first prospective evidence for a pain disparity in NAs that seems to be promoted by psychosocial, cardiometabolic, and pronociceptive mechanisms.

Native Americans (NAs) have a higher prevalence of chronic pain than other U.S. racial/ethnic groups, but there have been few attempts to understand the mechanisms of this pain disparity. This study used a comprehensive battery of laboratory tasks to assess peripheral fiber function (cool/warm detection thresholds), pain sensitivity (eg, thresholds/tolerances), central sensitization (eg, temporal summation), and pain inhibition (conditioned pain modulation) in healthy, pain-free adults (N = 155 NAs, N = 150 non-Hispanic Whites [NHWs]). Multiple pain stimulus modalities were used (eg, cold, heat, pressure, ischemic, and electric), and subjective (eg, pain ratings and pain tolerance) and physiological (eg, nociceptive flexion reflex) outcomes were measured. There were no group differences on any measure, except that NAs had lower cold-pressor pain thresholds and tolerances, indicating greater pain sensitivity than NHWs. These findings suggest that there are no group differences between healthy NAs and NHWs on peripheral fiber function, central sensitization, or central pain inhibition, but NAs may have greater sensitivity to cold pain. Future studies are needed to examine potential within-group factors that might contribute to NA pain risk.

Sexual assault (SA) is associated with an increased risk of chronic pain, but the mechanisms for this relationship are poorly understood. To explore whether disrupted descending inhibition is involved, this study used a conditioned pain modulation task to study the inhibition of pain and the nociceptive flexion reflex (NFR; a correlate of spinal nociception) in 32 pain-free SA survivors. This group was compared with 32 pain-free, trauma-exposed persons without SA and a group of 40 pain-free persons who reported no trauma exposure. Conditioned pain modulation was assessed from painful electric stimulations (test stimulus) delivered to the ankle before, during, and after participants submerged their hand in painful 10°C water (conditioning stimulus). Pain ratings and NFR were assessed in response to test stimuli. All groups demonstrated significant inhibition of pain during conditioned pain modulation. However, only the no trauma exposure group demonstrated significant inhibition of NFR. The persons without SA group showed no inhibition of NFR, whereas the SA group showed significant facilitation of the NFR. These findings suggest that trauma exposure may impair inhibitory cerebrospinal circuits, but that SA may specifically promote facilitation of spinal nociception. Perspective: This study suggests that trauma exposure disrupts the cerebrospinal inhibition of spinal nociception, but that exposure to SA further promotes chronic pain risk by facilitating spinal nociception. This finding help may help to elucidate the pain risk mechanisms in trauma survivors.

Native Americans (NAs) have a higher prevalence of chronic pain than any other U.S. racial/ethnic group; however, little is known about the mechanisms for this pain disparity. This study used quantitative sensory testing to assess pain experience in healthy, pain-free adults (n = 137 NAs (87 female), n = 145 non-Hispanic whites (NHW; 68 female)) after painful electric, heat, cold, ischemic, and pressure stimuli. After each stimulus, ratings of pain intensity, sensory pain, affective pain, pain-related anxiety, and situation-specific pain catastrophizing were assessed. The results suggested that NAs reported greater sensory pain in response to suprathreshold electric and heat stimuli, greater pain-related anxiety to heat and ischemic stimuli, and more catastrophic thoughts in response to electric and heat stimuli. Sex differences were also noted; however, with the exception of catastrophic thoughts to cold, these finding were not moderated by race/ethnicity. Together, findings suggest NAs experience heightened sensory, anxiety, and catastrophizing reactions to painful stimuli. This could place NAs at risk for future chronic pain and could ultimately lead to a vicious cycle that maintains pain (eg, pain → anxiety/catastrophizing → pain). Perspective NAs experienced heightened sensory, anxiety, and catastrophizing reactions in response to multiple pain stimuli. Given the potential for anxiety and catastrophic thoughts to amplify pain, this characteristic may place them at risk for pain disorders and could lead to a vicious cycle that maintains pain.

Native Americans (NAs) experience higher rates of chronic pain than the general U.S. population, but the risk factors for this pain disparity are unknown. NAs also experience high rates of stressors and cardiovascular and metabolic health disparities (eg, diabetes, cardiovascular disease) consistent with allostatic load (stress-related wear-and-tear on homeostatic systems). Given that allostatic load is associated with chronic pain, then allostatic load may contribute to their pain disparity. Data from 302 healthy, pain-free men and women (153 NAs, 149 non-Hispanic Whites [NHW]) were analyzed using structural equation modeling to determine whether cardiometabolic allostatic load (body mass index, blood pressure, heart rate variability) mediated the relationship between NA ethnicity and experimental measures of pronociceptive processes: temporal summation of pain (TS-pain) and the nociceptive flexion reflex (TS-NFR), conditioned pain modulation of pain (CPM-pain) and NFR (CPM-NFR), and pain tolerance. Results indicated that NAs experienced greater cardiometabolic allostatic load that was related to enhanced TS-NFR and impaired CPM-NFR. Cardiometabolic allostatic load was unrelated to measures of pain perception (CPM-pain, TS-pain, pain sensitivity). This suggests cardiometabolic allostatic load may promote spinal sensitization in healthy NAs, that is not concomitant with pain sensitization, perhaps representing a unique pain risk phenotype in NAs. Perspective: Healthy, pain-free Native Americans experienced greater cardiometabolic allostatic load that was associated with a pronociceptive pain phenotype indicative of latent spinal sensitization (ie, spinal sensitization not associated with hyperalgesia). This latent spinal sensitization could represent a pain risk phenotype for this population.

Threat-induced pain modulation can increase survival by amplifying physiological and behavioral reactions toward danger. Threat can also modulate spinal nociception, suggesting engagement of endogenous top-down circuitry. A unique method to assess spinal nociception is via reflex receptive fields (RRF) associated with the nociceptive withdrawal reflex (NWR, a protective spinally-mediated reflex). The size of nociceptive RRFs can be modulated by top-down circuitry with the enlargement of RRFs related to increased spinal nociception. Threat has been previously shown to enhance pain and spinal nociception, but the relationship between threat and RRFs has not been investigated. The present study investigated this issue in 25 healthy individuals. RRFs were determined from NWRs measured by electromyography of the tibialis anterior following electrocutaneous stimulations. RRFs and pain were assessed during periods in which participants were under threat of unpredictable painful abdominal stimulations and when they were not under threat. Results indicated that threat periods led to significantly higher pain, larger nociceptive RRFs and NWR magnitudes. These findings imply that threat produces changes in protective reflexes related to spinal nociceptive sensitivity and increased pain perception. This is likely mediated by top-down circuitry that enhances dorsal horn nociceptive neurons by enlarging RRFs and amplifying ascending pain signals. PERSPECTIVE: This article presents the enlargement of RRF during periods of threat. The results from this study may help clarify the mechanism underlining emotional modulation of spinal nociception.

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.

Emotion has a strong modulatory effect on pain perception and spinal nociception. Pleasure inhibits pain and nociception, whereas displeasure facilitates pain and nociception. Dysregulation of this system has been implicated in development and maintenance of chronic pain. The current study sought to examine whether emotional modulation of pain could be altered through the use of transcranial direct current stimulation (tDCS) to enhance (via anodal stimulation) or depress (via cathodal stimulation) cortical excitability in the dorsolateral prefrontal cortex. Thirty-two participants (15 female, 17 male) received anodal, cathodal, and sham tDCS on three separate occasions, followed immediately by testing to examine the impact of pleasant and unpleasant images on pain and nociceptive flexion reflex (NFR) responses to electrocutaneous stimulation. Results indicated that tDCS modulated the effect of image content on NFR, F(2, 2175.06) = 3.20, P= .04, with the expected linear slope following anodal stimulation (ie, pleasantneutralunpleasant) but not cathodal stimulation. These findings provide novel evidence that the dorsolateral prefrontal cortex is critical to emotional modulation of spinal nociception. Moreover, the results suggest a physiological basis for a previously identified phenotype associated with risk for chronic pain and thus a potentially new target for chronic pain prevention efforts. PERSPECTIVE: This study demonstrated that reduction of dorsolateral prefrontal cortical excitability by transcranial direct current stimulation attenuates the impact of emotional image viewing on nociceptive reflex activity during painful electrocutaneous stimulation. This result confirms there is cortical involvement in emotional modulation of spinal nociception and opens avenues for future clinical research.

Habituation (ie, decreases in responding) and sensitization (ie, increases in responding) after prolonged or repeated exposures to a fixed stimulus have been identified as important in adaptation to repeated or prolonged noxious stimulation. Determinants of habituation or sensitization are poorly understood, and experimental investigation of habituation of pain ratings have generally relied on pain reports and statistical techniques that average responses across a group of participants. Using a cross-sectional design, the current study used multilevel growth curve analyses to examine changes in the nociceptive flexion reflex (NFR), a spinal nociceptive withdrawal reflex, and pain ratings in response to 12 repeated, constant intensity, noxious electrocutaneous stimuli. Unconditional growth curve models indicated that, on average, participants evidenced habituation of the NFR and sensitization of pain ratings. However, a substantial subgroup of participants exhibited the opposite pattern of change. In conditional models, behavioral inhibition, b = .10, P = .003, and behavioral activation, b = −.07, P = .07, independently interacted with the growth curve to predict changes in NFR, but not pain ratings, across the 12 stimuli. These findings provide preliminary experimental support for Jensen and colleagues' 2-factor model of pain experience and implicate a role for approach and avoidance motivations in descending modulation of NFR. Perspective Using repeated NFR stimulation, this study showed that most participants exhibited NFR habituation and pain sensitization; however, a substantial subgroup showed an opposite pattern of pain habituation (25.0%) and NFR sensitization (31.4%). Further, NFR habituation was moderated by individual differences in behavioral activation and behavioral inhibition.

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 (i.e., central sensitization). Given that Native Americans (NA) are more likely to have ALEs, and 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; correlate of spinal hyperexcitability) and pain (TS-Pain) in 246 healthy, pain-free non-Hispanic whites (NHW) and Native Americans (NA). The Life Events Checklist (LEC-4) assessed 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 higher pain, but not enhanced TS-Pain. By contrast, ALEs were associated with enhanced TS-NFR. Race did not moderate these relationships. This implies that ALEs promote hyperalgesia as a result of increased spinal neuron excitability. Although relationships between ALEs and NFR/pain were not stronger in NAs, given prior evidence that NAs experience more ALEs, this might contribute to the higher prevalence of chronic pain in NAs. PERSPECTIVE: This study found a dose-dependent relationship between adverse life experiences (ALE) and spinal neuron excitability. Although the relationship was not stronger in Native Americans (NA) than non-Hispanic whites, given prior evidence that NAs experience more ALEs, this could contribute to the higher prevalence of chronic pain in NAs.

Compared to other racial/ethnic minority groups, Native Americans (NAs) are more likely to report experiences of discrimination and also have the highest prevalence of pain conditions. Thus, there is a need to understand how and why these disproportionately high rates occur. Discrimination has been conceptualized within the biopsychosocial model as a chronic psychosocial stressor that can lead to dysfunction of regulatory processes, such as pain. A recent study found that perceived discrimination increased psychological distress that, in turn, led to increased chronic pain. To date, these relationships have not yet been evaluated in NAs. The present study examined perceived discrimination, stress, and pain tolerance in healthy, pain-free NAs (N=112) and NHWs (N=128). Discrimination was measured with the Everyday Discrimination Scale (EDS), stress was measured with the Perceived Stress Scale (PSS), and pain tolerance was measured in reaction to cold, heat, electrocutaneous, and ischemia pain stimuli. Results indicated NAs experienced more discrimination than NHWs (p

Identification of those at risk for chronic pain development may help prevent its onset. The relationship between blood pressure (BP) and pain processing has been studied extensively, but it is unknown whether BP is related to future pain onset. The current study examined whether resting BP predicts the development of chronic pain in participants from the OK-SNAP study who were healthy and pain-free at the time of enrollment. BP was recorded 3 times and averaged at the time of enrollment. Following the OK-SNAP main study, participants were contacted every 6 months to assess for chronic pain. Of the 139 Native American (NA) and 147 non-Hispanic white (NHW) participants enrolled, 208 (73%) responded to at least 1 follow-up. Participants were deemed to have chronic pain if they experienced pain for >3 months that did not remit at subsequent follow-ups (N=35; 17%). These persons were compared to those that reported no persistent pain at any follow-up (N=133; 64%). First, zero-order correlations were conducted between chronic pain onset, BP, and control variables. Systolic BP, diastolic BP, race, general health perception, and age were significantly related to chronic pain onset (ps

The tendency to inhibit anger (anger-in) is associated with increased pain. This relationship may be explained by the negative affectivity hypothesis such that those with high anger-in experience increased negative affectivity and thus increased pain (because negative affect enhances pain). Alternatively, this relationship may be explained by the cognitive resource hypothesis such that anger-in limits attentional resources normally available for pain modulation. The present study examined these competing hypotheses in healthy, pain-free participants using a well-validated picture viewing paradigm (ie, Emotional Controls of Nociception, ECON). ECON is a paradigm in which painful, electrocutaneous stimulations are delivered during and in between pictures of emotional content (mutilation, neutral, and erotica). Pain ratings were assessed in response to electric stimuli. This allows for the assessment of emotional modulation of pain by comparing pain evoked during mutilation and erotic pictures to pain evoked during neutral pictures. Additionally, ECON allows for the assessment of attentional modulation of pain by comparing pain evoked during neutral pictures (distraction) to pain evoked in the absence of pictures (control). Prior to ECON, participants filled out the Anger Expression Inventory to assess their tendency to inhibit anger and 2 groups were formed (high anger-in, N = 71 and low anger-in, N = 27) from their responses (ie, +/- 1SD from the normative mean of anger-in). Results found that both groups demonstrated similar emotional modulation of pain. By contrast, persons in the low anger-in group displayed attentional modulation of pain, whereas persons in the high anger-in group failed to attentionally modulate pain. These findings suggest that cognitive resource deficits in high anger-in individuals may contribute to increased pain risk.

Pain catastrophizing is associated with enhanced pain; however, the mechanisms by which it modulates pain are poorly understood. Evidence suggests that catastrophizing modulates supraspinal processing of pain but does not modulate spinal nociception (as assessed by nociceptive flexion reflex [NFR]). Unfortunately, most NFR studies have been correlational. To address this, this study experimentally reduced catastrophizing to determine whether it modulates spinal nociception (NFR). Healthy pain-free participants (N = 113) were randomly assigned to a brief 30-minute catastrophizing reduction manipulation or a control group that received pain education. Before and after manipulations, 2 types of painful stimuli were delivered to elicit (1) NFR (single trains of stimuli) and (2) temporal summation of NFR (3 stimulations at 2 Hz). After each set of stimuli, participants were asked to report their pain intensity and unpleasantness, as well as their situation-specific catastrophizing. Manipulation checks verified that catastrophizing was effectively reduced. Furthermore, pain intensity and unpleasantness to both stimulation types were reduced by the catastrophizing manipulation, effects that were mediated by catastrophizing. Although NFRs were not affected by the catastrophizing manipulation, temporal summation of NFR was reduced. However, this effect was not mediated by catastrophizing. These results indicate that reductions in catastrophizing lead to reductions in pain perception but do not modulate spinal nociception and provides further evidence that catastrophizing modulates pain at the supraspinal, not the spinal, level.

In healthy individuals, emotions modulate pain and spinal nociception according to a valence linear trend (ie, pain/nociception is highest during negative emotions and lowest during positive emotions). However, emerging evidence suggests that emotional modulation of pain (but not spinal nociception) is disrupted in fibromyalgia and disorders associated with chronic pain risk (eg, major depression, insomnia). The present study attempted to extend this work and to examine whether women with premenstrual dysphoric disorder (PMDD), a cyclical syndrome associated with debilitating affective symptoms during the late-luteal (premenstrual) phase of the menstrual cycle, is also associated with disrupted emotional modulation of pain. To do so, an affective picture-viewing procedure was used to study emotional modulation of pain and spinal nociception in 14 women with PMDD and 14 control women during mid-follicular, ovulatory, and late-luteal phases of the menstrual cycle (verified by salivary hormone levels and luteinizing hormone tests). At each phase, mutilation, neutral, and erotic pictures were presented to manipulate emotion. During picture viewing, suprathreshold electrocutaneous stimuli were presented to evoke pain and the nociceptive flexion reflex (NFR; a physiological measure of spinal nociception). Statistically powerful linear mixed model analyses confirmed that pictures evoked the intended emotional states in both groups across all menstrual phases. Furthermore, emotion modulated pain and NFR according to a valence linear trend in both groups and across all menstrual phases. Thus, PMDD-related affective disturbance is not associated with a failure to emotionally modulate pain, suggesting that PMDD does not share this pain phenotype with major depression, insomnia, and fibromyalgia.

Trauma exposure, especially sexual assault (SA), is highly correlated with pain conditions, in that many chronic pain samples report trauma histories. However, our understanding of the mechanisms behind this relationship is limited. Previous findings from our lab suggest that SA disrupts descending pain modulation. However, to date, no study has used quantitative sensory testing (QST) to comprehensively assess the pain system in SA survivors. 41 healthy, pain-free SA survivors were matched to a group of 41 healthy, pain-free trauma exposed persons without SA (TE). These groups were compared to a group of healthy, pain-free persons with no trauma history (no-TE; N=62). QST included warm, cool, heat, cold, ischemia, and electric thresholds, and heat, cold, ischemia, and electric tolerances. The nociceptive flexion reflex (NFR) threshold was used to assess spinal nociception. Results suggested SA survivors had higher cool thresholds than the TE and no-TE groups. Moreover, SA survivors had lower cold thresholds, cold tolerances, and heat tolerances than no-TE. Surprisingly, SA survivors had higher ischemia tolerances than no-TE and TE groups. The TE group had lower heat and cold tolerances than the no-TE group. None of the other group differences were significant for any pain outcome. These findings suggest that SA is associated with greater sensitivity in A-delta fibers (cool thresholds) and hyperalgesia in response to thermal stimuli (heat, cold). However, hypoalgesia was noted in response to deep tissue pain (ischemia). By contrast, TE is primarily associated with reduced tolerance to heat and cold. These group differences are not likely due to spinal sensitization due to the lack of group differences in NFR. Future studies are needed to replicate these findings and determine whether QST responses can predict negative sequela of SA and non-SA trauma exposure.

Previous research has explored cultural differences concerning the prevalence, response, and treatment preferences of individuals experiencing pain. However, the meaning of these painful experiences has not been comprehensively examined. Research tends to generalize findings from predominantly European American samples and assume universality of their findings across cultures. Numerous studies have demonstrated a significantly higher prevalence of physical pain in Native Americans (NA) compared to non-Hispanic Whites (NHW). Because of this, it is important to consider whether our current understanding of painful experiences is indeed universal. To accomplish this, a semi-structured interview was administered to 156 NAs and 151 NHWs that asked open-ended questions related to: words used to describe physically injurious experiences, the purpose of pain, individual and culture-specific pain meaning, and words for the opposite of pain. Next, themes were generated from transcripts and two raters blind to participants’ racial/ethnic group coded transcripts for the themes. Strong agreement between raters was obtained (Kappa= .75-1.00). Chi-square analyses assessed whether the frequency of responses for themes were different between NHWs and NAs. In general, frequency of themes were similar between groups; nonetheless, a few small group differences were noted. NHWs used the word pain more often to describe physically hurtful experiences (45.3% vs. 42.1%; χ 2 [1, N=309]=4.675, p 2 [1, N=309]=7.320, p 2 [1, N=309]=13.310, p

Chronic pain results in tremendous economic and psychological burden. Thus, an ability to identify individuals at risk for chronic pain onset could be an important first step in reducing this burden. One mechanism that may contribute to pain onset is impaired descending pain inhibition. The present study examined whether the efficiency of descending inhibition (as measured by conditioned pain modulation, CPM) predicted future chronic pain onset in a sample of participants who were healthy and pain-free at the time of enrollment in OK-SNAP. Chronic pain onset was determined prospectively from follow-up surveys administered every 6-months following enrollment. Of the 139 Native American (NA) and 147 non-Hispanic white (NHW) participants enrolled, 208 (73%) responded to ≥1 follow-up. Participants were said to have developed chronic pain if they experienced persistent pain for >3 months and the pain did not remit at subsequent follow-ups (N=34, 16%). 174 persons did not develop chronic pain. CPM was assessed from painful electric stimulations delivered before and during hand/forearm submersion in 10˚C water. Pain ratings and nociceptive flexion reflexes (NFR; correlate of spinal nociception) were assessed in response to electric stimuli. CPM efficiency = change in pain/NFR. CPM of pain and NFR were entered as predictors in a logistic regression that controlled for race (NA vs. NHW), age, BMI, sex, general health, depression, anxiety, and somatization. Interactions between race and CPM efficiency were examined as well. Results found less efficient CPM of NFR (OR=6.53, 95%CI: 1.04, 40.95) and more depressive symptoms (OR=10.22, 95%CI: 1.28, 81.36) at enrollment predicted chronic pain onset. The model explained 34.5% of the variance (Nagelkerke R2=.345). Interactions of CPM variables with race were not significant. These findings imply that impaired descending inhibition of spinal nociception (NFR) may play a role in the development of chronic pain.

Slow breathing is used as a means to reduce pain, yet the mechanisms responsible for respiration-induced hypoalgesia are poorly understood. The present study asked 30 healthy partici- pants (Mage = 21 years, Meducation = 15 years, 80% white non-Hispanic) to breathe at normal, slow (50% normal), and fast (125% normal) rates while constant-intensity, suprathreshold electric stimu- lations were delivered to the sural nerve to elicit pain and the nociceptive flexion reflex (NFR, a mea- sure of spinal nociception). Stimulations were equally balanced across inhalations and exhalations to determine whether parasympathetic activation during exhalations contributes to hypoalgesia. Respi- ration rate, heart rate variability (HRV, a measure of parasympathetic activity), heart rate, and subjec- tive arousal were assessed as manipulation checks. Slow breathing reduced pain relative to normal breathing and fast breathing, but NFR was not influenced by breathing. Further, pain and NFR did not differ between exhalations and inhalations, and changes in HRV did not correlate with changes in pain or NFR. Together, these findings suggest that respiration-induced hypoalgesia does not re- quire gating of spinal nociception or changes in parasympathetic activity. Perspective: Slow breathing reduced pain relative to normal and fast breathing. This respiration- induced hypoalgesia does not appear to be due to gating of spinal nociception or changes in para- sympathetic activity.

Study Objectives: Evidence supports the use of cognitive behavioral therapies for nightmares in trauma-exposed individuals. This randomized clinical trial replicated a study of exposure, relaxation, and rescripting therapy (ERRT) and extended prior research by including broad measures of mental health diffi culties, self-reported physical health problems, and quality of life. Additionally, physiological correlates of treatment-related change assessed from a script-driven imagery paradigm were examined. Methods: Forty-seven individuals were randomized to treatment or waitlist control. Results: The treatment group demonstrated improvements relative to the control group at the one-week post-treatment assessment. At the 6-month follow-up assessment, signifi cant improvements were found for frequency and severity of nightmares, posttraumatic stress disorder symptoms, depression, sleep quality and quantity, physical health symptoms, anger, dissociation, and tension reduction behaviors. Participants also reported improved quality of life. Treatment-related decreases in heart rate to nightmare imagery were correlated with improvements in sleep quality and quantity; treatment-related decreases in skin conductance to nightmare imagery were correlated with improvements in nightmare severity, posttraumatic stress disorder symptom severity, sleep quality, and fear of sleep; and treatment-related decreases in corrugator activity to nightmare imagery were correlated with improved physical health. Conclusions: Findings provide additional support for the use of ERRT in treating nightmares and related diffi culties and im

The August 2010 issue of Journal of Clinical Sleep Medicine (Vol. 6, No. 4) included an article suggesting treatment recommendations for adult nightmare disorder. Although we appreciate the work by the authors, we were left with three basic concerns about the methodology utilized and results found. First, works providing evidence for some of the treatments were not reported in the original article. Second, search methodology in the original article was not used consistently at updated time points. Third, the original article only utilized results obtained from PubMed and did not consider other databases. The current study sought to replicate the methodology and compare findings as well as expand by equalizing search methodology across updated time points. The present study expands the original efforts further by conducting article searches again on PsycINFO. Consequent changes to evidence levels and recommendations are discussed.

The nociceptive flexion reflex (NFR) is a physiological tool to study spinal nociception. However, NFR assessment can take several minutes and expose participants to repeated suprathreshold stimulations. The 4 studies reported here assessed the reliability and validity of a brief method to assess NFR threshold that uses a single ascending series of stimulations (Peak 1 NFR), by comparing it to a well-validated method that uses 3 ascending/descending staircases of stimulations (Staircase NFR). Correlations between the NFR definitions were high, were on par with test-retest correlations of Staircase NFR, and were not affected by participant sex or chronic pain status. Results also indicated the test-retest reliabilities for the 2 definitions were similar. Using larger stimulus increments (4 mAs) to assess Peak 1 NFR tended to result in higher NFR threshold estimates than using the Staircase NFR definition, whereas smaller stimulus increments (2 mAs) tended to result in lower NFR threshold estimates than the Staircase NFR definition. Neither NFR definition was correlated with anxiety, pain catastrophizing, or anxiety sensitivity. In sum, a single ascending series of electrical stimulations results in a reliable and valid estimate of NFR threshold. However, caution may be warranted when comparing NFR thresholds across studies that differ in the ascending stimulus increments. Perspective This brief method to assess NFR threshold is reliable and valid; therefore, it should be useful to clinical pain researchers interested in quickly assessing inter- and intra-individual differences in spinal nociceptive processes.

Pain catastrophizing is associated with enhanced temporal summation of pain (TS-Pain). However, because prior studies have found that pain catastrophizing is not associated with a measure of spinal nociception (nociceptive flexion reflex [NFR] threshold), this association may not result from changes in spinal nociceptive processes. The goal of the present study in healthy participants was to examine the relationship between trait (traditional) and state (situation-specific) pain catastrophizing and temporal summation of NFR (TS-NFR) and TS-Pain. A secondary goal was to replicate prior findings concerning relationships between catastrophizing and NFR threshold, electrocutaneous pain threshold, and sensory and affective ratings of electrocutaneous stimuli. All analyses controlled for depression symptoms, pain-related anxiety, and participant sex. As expected, multiple regression analyses indicated that neither trait nor situation-specific catastrophizing was associated with NFR threshold, but that situation-specific catastrophizing was associated with pain ratings. Multilevel linear growth models of TS data indicated that situation-specific catastrophizing was associated with TS-Pain but not TS-NFR. Trait catastrophizing was not related to TS-Pain or TS-NFR. Together, these results confirm prior studies that indicate that catastrophizing enhances pain via supraspinal processes rather than spinal processes. Moreover, because catastrophizing was associated with TS-Pain but not TS-NFR, caution is warranted when using pain ratings to infer temporal summation of spinal nociceptive processes.

Research indicates pain may be influenced by the menstrual cycle. While the mechanisms underlying these effects are unclear, it is possible that menstrual phase-related changes in endogenous pain modulation contribute. The present study used well-validated methods to study affective modulation of pain and the nociceptive flexion reflex (NFR) in healthy women during two menstrual phases (mid-follicular vs. late-luteal). Women (N = 41) tracked their menstrual phases for three complete cycles and were asked to attend two laboratory testing sessions in the second and third cycles to assess affective modulation of pain and nociception (testing order counterbalanced). Menstrual phase was assessed from daily diaries, luteinizing hormone tests, and basal body temperature. At each session, emotionally charged pictures were presented and suprathreshold electrocutaneous stimulations were delivered during and in between pictures. Subjective and physiological emotional reactions were recorded in response to each picture and pain ratings and NFRs were recorded in response to each suprathreshold stimulus. Results suggested pictures effectively manipulated emotion in both menstrual phases. Moreover, arousing unpleasant pictures enhanced pain and NFR, whereas arousing pleasant pictures inhibited pain and NFR. These modulatory effects were similar in both menstrual phases. Together, these findings suggest that affective engagement of corticospinal mechanisms does not differ across these phases of the menstrual cycle. However, future research is needed to directly assess the relationship between affective modulation of pain/nociception and inter- and intra-individual differences in ovarian hormones and to extend these findings to women who suffer from menstrual cycle-related pain (e.g., premenstrual dysphoric disorder, fibromyalgia).

Fibromyalgia syndrome (FMS) is a chronic pain disorder associated with widespread musculoskeletal pain, tenderness, and fatigue. Additionally, correlational research suggests negative affect (eg, depression, anxiety) and deficits in positive affect may contribute to FMS symptomatology. However, well-controlled, experimental research is necessary to ascertain whether patients with FMS have problems in affective processing. The present study used a well-validated picture-viewing paradigm to evoke emotional responses in 17 patients with FMS and 17 sex- and age-matched healthy control participants. Each participant viewed pleasant (erotica), neutral, and unpleasant (attack related) pictures, and abrupt white noises were delivered during two-thirds of the pictures to evoke startle eyeblinks. Appetitive and defensive responding was assessed from subjective (valence/pleasure and arousal ratings) and physiological (corrugator EMG, heart rate, skin-conductance response, startle-reflex modulation) reactions to pictures. Results suggested FMS was associated with greater defensive activation (displeasure, subjective arousal, corrugator EMG) to the unpleasant, threat-related pictures, but not deficits in appetitive activation to erotic pictures. Although preliminary, these data suggest individuals with FMS have deficits in affective processing, but this dysregulation may be limited to defensive activation. Implications for treatment and future research are discussed. Perspective Fibromyalgia is a debilitating disease associated with affective distress. Results from the present study suggest that FMS is associated with enhanced defensive activation to nonpainful threat-related stimuli, but not deficits in appetitive reactions to erotic stimuli. These findings have implications for the treatment and study of FMS.

Physiological reactions to noxious stimuli are often used to make inferences about pain, but few studies have thoroughly examined the intra- and interindividual relationships between them. In the present study (N=104), multilevel analyses was used to assess relations between physiological (nociceptive flexion reflex magnitude [NFR], blink reflex magnitude, skin conductance response [SCR], heart rate [HR]) and subjective reactions to electrocutaneous stimuli. All physiological reactions were significant predictors of ratings when entered alone, explaining 1% (SCR) to 29% (NFR) of the variance; but only NFR, blink, and HR were significant in a multivariate predictor model. Significant interindividual variability in slopes was found for blink and HR, but not NFR. A final trimmed model that included NFR, blink, and the blink random slope explained 35% of the variance in ratings.

Prior research suggests emotional picture-viewing modulates motoric (nociceptive flexion reflex), autonomic (skin conductance response, heart rate acceleration), and subjective (pain rating) reactions to noxious electrodermal stimulation. The present study sought to determine whether emotional valence and arousal contribute to nociception modulation. To do so, pictures varying in emotional content (erotica, food, neutral, loss, attack) were chosen to manipulate emotional valence (pleasant = erotic and food; unpleasant = loss and attack) and arousal (low = food and loss; moderate = erotica and attack). Pictures were presented in pseudorandom order to elicit emotional processing while noxious electric stimulations were delivered to the sural nerve. Nociceptive flexion reflex (NFR) magnitude, skin conductance response (SCR), heart rate (HR) acceleration, and subjective pain ratings to each stimulation were measured, standardized, averaged by picture content, and analyzed. Results suggested that picture-viewing explained 52% of the variance in the multivariate combination of the nociceptive reactions and modulated them in parallel. Pleasant pictures inhibited reactions, whereas unpleasant pictures enhanced them. However, only erotica and attack pictures elicited significant modulation relative to neutral pictures, suggesting arousal also contributed. An exploratory multilevel analysis also supported this conclusion. Together, these data suggest emotional control of nociceptive reactions (ECON) is associated with a valence-byarousal interaction. Implications of these findings for how emotional picture-viewing can be used to study supraspinal modulation are discussed. � 2007 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Emotionally charged facial expressions (happy, fear) served as conditioned stimuli in a differential fear conditioning procedure. Expressions were presented in pseudo-random order on a computer monitor. For half of the participants, the fear expression was paired with an aversive electric stimulation (UCS), whereas the happy expression was unpaired. The other participants had the opposite pairing. To assess the influence of conditioned fear on pain, expressions were shown again in the absence of the UCS and pain threshold was assessed during each expression. The latency of finger withdrawal from a radiant heat device was used to index pain threshold. Skin conductance response (SCR) and self-reported emotion were measured to assess fear conditioning. Consistent with preparedness theory, differential fear conditioning was only present when the fear expression was paired with the UCS. Moreover, pain threshold was only influenced by fear conditioning in persons for whom the fear expression was paired with the UCS. Specifically, finger withdrawal latencies were lower (suggesting hyperalgesia) during the fear expression than during the happy expression; an effect that was not present before CSUCS pairing. This work suggests that some stimuli are more readily associated with an aversive event and can lead to pain enhancement. Perspective: Although preliminary, these results suggest that fear-relevant environmental stimuli (including facial expressions) may provide important environmental cues during aversive events that influence the level of pain experienced.

Despite the widespread use of the nociceptive flexion reflex (NFR) paradigm in clinical and experimental pain research, there is currently no consensus on how best to define NFR threshold. Accordingly, the present studies were designed to assess the accuracy and reliability of different NFR threshold scoring criteria. Study 1 compared 13 scoring criteria in their accuracy for identifying the presence of the NFR, then generated empirically derived cut-points for the best criteria, and examined the test-retest reliability of NFR thresholds derived from these cut-points. Study 2 evaluated the replicability of these findings in an independent sample. Results from the two studies suggested that standardized peak (NFR Interval Peak z score) and mean (NFR Interval z score) biceps femoris electromyogram (EMG) activity were accurate and reliable criteria for defining NFR threshold. Acknowledging that cut-points may need to be adjusted for different research designs, graphs depicting sensitivity and specificity across a range of cut-points have been provided to facilitate researcher’s decision-making. It is hoped that the results of these studies will promote a standard NFR threshold assessment methodology, and further encourage the application of the NFR paradigm in the investigation of mechanisms and characteristics of both painful and non-painful diseases.

Prior research has found that pain catastrophizing measured before pain testing is not correlated with the nociceptive flexion reflex (NFR) threshold (a measure of spinal nociception), suggesting that catastrophizing does not alter pain through descending modulatory mechanisms. However, recent evidence suggests that in vivo catastrophizing (measured during or after pain testing) is a better predictor of pain outcomes. In the present study, NFR threshold and pain sensation ratings were assessed in 78 healthy participants by delivering electric stimulations to the sural nerve. After pain testing, participants were asked to rate their affective reaction (displeasure, arousal) to electric stimuli and to report on their pain catastrophizing. Hierarchical regression analyses controlling for participant sex, pre-experiment affect, depressive symptoms, and self-efficacy were used to predict pain-related outcomes (NFR threshold, pain sensation, displeasure ratings, arousal ratings) from in vivo catastrophizing scores. Results indicated that in vivo catastrophizing was related to pain sensation but not to NFR thresholds or arousal reactions. The relation between in vivo catastrophizing and displeasure ratings was not significant after other variables were controlled. These data support prior research suggesting that catastrophizing does not alter pain by engaging descending modulatory mechanisms. Perspective Pain catastrophizing is an important psychological predictor of pain and pain-related functioning. The present study confirms prior reports suggesting that catastrophizing does not work by engaging mechanisms that alter pain transmission in the spinal cord before the signal travels to the brain.

Objective.—The primary objectives of the present study were to (1) contrast reproductive hormone levels and ratings of menstrual distress of female migraineurs with those of a control group in each menstrual cycle phase, (2) examine correlations between hormone levels and migraine frequency, severity, and migraine-related disability, and (3) examine correlations between menstrual distress and migraine frequency, severity, and migraine-related disability. A secondary objective was to evaluate the validity of a migraine disability measure modified to reflect 7-day recall. Background.—Further controlled, prospective study is needed regarding the temporal relationships between reproductive hormones at each stage of the menstrual cycle and fluctuations in migraine activity across the cycle. Methods.—Twenty-three women (17 with migraine, 6 control participants) completed laboratory hormone assays and measures of menstrual distress and disability at each phase of one menstrual cycle, and monitored their headache activity daily during the same cycle. Results.—The migraine group evidenced lower premenstrual luteinizing hormone and more menstrual distress symptoms at each phase of the menstrual cycle. Hormones were associated with migraine activity and disability within cycle phases, and across phases in a time-lagged manner. Menstrual distress was associated with ovulatory phase migraine activity and with migraine-related disability across the menstrual cycle. A retrospective 7-day migraine disability measure appeared to be a consistently valid index. Conclusions.—Both reproductive hormones and menstrually related distress appear to predict migraine activity and disability. These associations were evident not only for perimenstrual migraine, but also for migraine at each phase of the menstrual cycle. Ke yw ords: hormones, migraine, menstrual cycle, distress, disability Abbreviations: BBT basal body temperature, HDI headache disability inventory, LH luteinizing hormone, MDQ menstrual distress questionnaire, MIDAS migraine disability assessment, d Cohen’s effect size

Prior research indicates that exposure to fear-inducing stimuli inhibits finger withdrawal to sudden onset and high intensity radiant heat in humans. Although withdrawal latencies to intense heat are thought to reflect changes in spinal nociceptive processing, supraspinal measures are needed to determine whether pain perception is altered. The present study used gradual onset and low intensity radiant heat to induce a finger withdrawal response that depends on supraspinal processes. After baseline pain threshold tests, 57 healthy human participants were randomly assigned to 1 of 2 groups. In the fear group, participants received 3 brief shocks. In the neutral group, participants did not receive shock. Results suggest that finger withdrawal latencies to low intensity heat were increased after shock presentation, providing additional evidence that fear reduces pain on a measure that is influenced by supraspinal processes. Both self-report and physiological (skin conductance level, heart rate, and blood pressure) measures of emotion confirmed that the intended affective states were induced. Finger temperature was unaffected by emotion manipulations; thus, skin cooling does not appear to mediate increased withdrawal latencies. These findings provide additional evidence that fear not only inhibits spinal nociceptive reflexes, it also inhibits supraspinal measures of pain. Perspective From a clinical perspective, these data suggest that patients who experience intense fear in response to unpredictable threatening events will show a reduction in pain perception.

Prior work indicates that exposure to fear-inducing shock inhibits finger-withdrawal to radiant heat in humans (hypoalgesia), whereas anxiety induced by threat of shock enhances reactivity (hyperalgesia; Pain 84 (2000) 65-75). Although finger-withdrawal latencies are thought to reflect changes in pain sensitivity, additional measures of pain are needed to determine whether pain perception is altered. The present study examined the impact of negative affect on visual analog scale (VAS) ratings of fixed duration thermal stimuli. One hundred twenty-seven male and female human subjects were randomly assigned to one of three emotion-induction conditions: (1) negative affect induced by exposure to three brief shocks; (2) negative affect elicited by the threat of shock without presentation; and (3) neutral affect, with no intervention. VAS ratings were tested before and after emotion-induction. Results suggest that both negative affect manipulations reduced pain. Manipulation checks indicated that the emotion-induction treatments induced similar levels of fear but with different arousal levels. Potential mechanisms for affect induced changes in pain are discussed.

Considerable animal research suggests that exposure to noxious and nonnoxious fear-inducing stimuli can produce hypoalgesia. Although this effect is thought to generalize across species, only a few studies have examined the pain modulatory effects of nonnoxious fear-eliciting stimuli in humans. The present study examined whether exposure to a series of loud noise bursts would produce a fear-related hypoalgesia in male and female human subjects. Both subjective and physiologic measures (skin conductance level, heart rate) indicated that noise exposure resulted in fear, sympathetic arousal, and decreased pain reactivity in women (n = 20). In contrast, men (n = 20) did not experience fear or physiologic arousal, but reacted with surprise and increased pain reactivity. These findings provide additional evidence that hypoalgesia is mediated by fear and physiologic arousal. Although future studies should directly manipulate surprise, it appears that surprise without fear and physiologic arousal might enhance pain processing.

Major depressive disorder (MDD) is associated with risk for chronic pain, but the mechanisms contributing to the MDD and pain relationship are unclear. To examine whether disrupted emotional modulation of pain might contribute, this study assessed emotional processing and emotional modulation of pain in healthy controls and unmedicated persons with MDD (14 MDD, 14 controls). Emotionally charged pictures (erotica, neutral, mutilation) were presented in 4 blocks. Two blocks assessed physiological-emotional reactions (pleasure/arousal ratings, corrugator electromyography (EMG), startle modulation, skin conductance) in the absence of pain and 2 blocks assessed emotional modulation of pain and the nociceptive flexion reflex (NFR, a physiological measure of spinal nociception) evoked by suprathreshold electric stimulations. Results indicated pictures generally evoked the intended emotional responses; erotic pictures elicited pleasure, subjective arousal, and smaller startle magnitudes, whereas mutilation pictures elicited displeasure, corrugator EMG activation, and subjective/physiological arousal. However, emotional processing was partially disrupted in MDD, as evidenced by a blunted pleasure response to erotica and a failure to modulate startle according to a valence linear trend. Furthermore, emotional modulation of pain was observed in controls but not MDD, even though there were no group differences in NFR threshold or emotional modulation of NFR. Together, these results suggest supraspinal processes associated with emotion processing and emotional modulation of pain may be disrupted in MDD, but brain to spinal cord processes that modulate spinal nociception are intact. Thus, emotional modulation of pain deficits may be a phenotypic marker for future pain risk in MDD.