Search

Background Opioid analgesics are commonly prescribed for postoperative analgesia following pediatric surgery and often result in leftover opioid analgesics in the home. To reduce the volume of leftover opioids and overall community opioid burden, the State of Tennessee enacted a policy to reduce initial opioid prescribing to a 3-day supply for most acute pain incidents. We aimed to evaluate the extent of leftover opioid analgesics following pediatric ambulatory surgeries in the context of a state-mandated restrictive opioid-prescribing policy. We also aimed to evaluate opioid disposal rates, methods of disposal, and reasons for nondisposal. Methods Study personnel contacted the parents of 300 pediatric patients discharged with an opioid prescription following pediatric ambulatory surgery. Parents completed a retrospective telephone survey regarding opioid use and disposal. Data from the survey were combined with data from the medical record to evaluate proportion of opioid doses prescribed that were left over. Results The final analyzable sample of 185 patients (62% response rate) were prescribed a median of 12 opioid doses (interquartile range [IQR], 12-18), consumed 2 opioid doses (IQR, 0-4), and had 10 opioid doses left over (IQR, 7-13). Over 90% (n = 170 of 185) of parents reported they had leftover opioid analgesics, with 83% of prescribed doses left over. A significant proportion (29%, n = 54 of 185) of parents administered no prescribed opioids after surgery. Less than half (42%, n = 71 of 170) of parents disposed of the leftover opioid medication, most commonly by flushing down the toilet, pouring down the sink, or throwing in the garbage. Parents retaining leftover opioids (53%, n = 90 of 170) were most likely to keep them in an unlocked location (68%, n = 61 of 90). Parents described forgetfulness and worry that their child will experience pain in the future as primary reasons for not disposing of the leftover opioid medication. Conclusions Despite Tennessee's policy aimed at reducing leftover opioids, a significant proportion of prescribed opioids were left over following pediatric ambulatory surgeries. A majority of parents did not engage in safe opioid disposal practices. Given the safety risks related to leftover opioids in the home, further interventions to improve disposal rates and tailor opioid prescribing are warranted after pediatric surgery.

Background Patient-reported opioid use is an important outcome for studies of postoperative pain and opioid use, however the accuracy of patient-reported opioid use is unknown. Objective To evaluate the accuracy of retrospective patient-reported analgesic use versus real-time analgesic use data obtained via electronic medication caps. Study Design This study used a descriptive cross-sectional study design. Data from 132 patients who underwent cesarean delivery at a metropolitan academic medical center were analyzed to compare 2 methods of measuring opioid consumption postoperatively. At discharge, patients received 30 5-mg hydrocodone/325-mg acetaminophen tablets in electronically enabled Smart Cap bottles that recorded medication bottle access. Patients were phoned 2 weeks post-discharge to assess patient-report of opioid use over the post-discharge period. Intra-class correlations (ICCs) were used to assess correspondence between retrospective patient-reported opioid use and Smart Cap data. Likelihood Chi-Square tests assessed differences between demographic and clinical characteristics in persons who accurately, over-, and under-reported opioid use as compared to Smart Cap data. Results Participants ranged from 18-41 years old (mean 30.6), and most (74% [92/124] were Caucasian with private or military insurance (66% [80/122]). Patient-reported opioid use corresponded highly with Smart Cap data (ICC = .85, 95% C.I.=.80-.90, p Conclusions Retrospective self-reporting is a reasonably accurate method to assess opioid use over a 2-week time period after cesarean delivery.

We tested whether aerobic exercise training altered morphine analgesic responses or reduced morphine dosages necessary for adequate analgesia. Patients with chronic back pain were randomized to an 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 45). Before and after the intervention, participants underwent 3 laboratory sessions (double-blinded, crossover) to assess effects of saline placebo, i.v. morphine (0.09 mg/kg), and i.v. naloxone (12 mg) on low back pain and evoked heat pain responses. Differences in evoked and back pain measures between the placebo and morphine conditions indexed morphine analgesia, with pre-post intervention changes the primary outcome. Endogenous opioid analgesia was indexed by differences in evoked and low back pain measures between the naloxone and placebo conditions. A Sex X Intervention interaction on the analgesic effects of morphine on visual analogue scale back pain intensity was observed (P = 0.046), with a similar trend for evoked pain threshold (P = 0.093). Male exercisers showed reduced morphine analgesia pre-post intervention, whereas male controls showed increased analgesia (with no differences in females). Of clinical significance were findings that relative to the control group, aerobic exercise produced analgesia more similar to that observed after receiving ≈7 mg morphine preintervention (P < 0.045). Greater pre-post intervention increases in endogenous opioid function (from any source) were significantly associated with larger pre-post intervention decreases in morphine analgesia (P < 0.046). The overall pattern of findings suggests that regular aerobic exercise has limited direct effects on morphine responsiveness, reducing morphine analgesia in males only.

Migraine headache is a pain condition characterized by severe and recurrent unilateral head pain. Among other mechanisms, central pain sensitization processes seem to be involved in the disorder. An experimental protocol based on slowly repeated evoked pain (SREP) has been shown to indicate pain sensitization in fibromyalgia patients and differentiate these patients from healthy individuals and rheumatoid arthritis patients. This study examined SREP sensitization in migraine patients and explored its potential usefulness as a central sensitization marker. The SREP protocol was administered to 40 episodic migraine (EM) patients not currently experiencing a headache and 40 healthy controls. SREP consisted of a series of 9 suprathreshold painful pressure stimuli of 5 s duration and a 30 s interstimulus interval. SREP sensitization was indexed by the increase in pain ratings across the stimuli. Pain threshold, pain tolerance and temporal summation of pain were also assessed. SREP sensitization was observed in EM, but not in healthy individuals (p

Objective Fibromyalgia is a chronic pain syndrome characterized by central sensitization. A novel protocol based on slowly repeated evoked pain (SREP) appears to be a useful marker of pain sensitization in fibromyalgia patients. Whether SREP enhances diagnostic accuracy beyond key clinical symptoms that characterize fibromyalgia has not been examined. Methods Fifty fibromyalgia patients, 30 rheumatoid arthritis patients, and 50 healthy individuals were evaluated to assess clinical pain, as well as fatigue, insomnia, pain catastrophizing, and negative mood. The SREP protocol consisted of a series of nine low-intensity painful pressure stimuli of five seconds’ duration with 30-second interstimulus intervals. SREP sensitization was indexed by increases in pain intensity ratings across stimuli. Results SREP sensitization was observed in fibromyalgia but not in rheumatoid arthritis or healthy individuals. As expected, fibromyalgia patients exhibited a more negative psychosocial profile than did rheumatoid arthritis patients and healthy individuals. SREP was positively associated with clinical pain, fatigue, insomnia, and catastrophizing, but not with negative mood. SREP discriminated fibromyalgia cases from rheumatoid arthritis and healthy individuals even when current clinical pain was included in the analysis. Combining fatigue, insomnia, and SREP led to near perfect diagnostic accuracy (99%) in differentiating fibromyalgia from healthy individuals and 86.3% accuracy in discriminating fibromyalgia from rheumatoid arthritis. Conclusions These results provide further evidence of SREP as a marker of pain sensitization in fibromyalgia and suggest that it captures aspects of fibromyalgia not fully captured by clinical features. Combining SREP with assessment of clinical features could potentially improve fibromyalgia diagnosis.

BACKGROUND/OBJECTIVES: Inner-city Black women may be more susceptible to post-traumatic stress disorder (PTSD) than White women, although mechanisms underlying this association are unclear. Living in urban neighborhoods distinguished by higher chronic stress may contribute to racial differences in women’s cognitive, affective, and social vulnerabilities, leading to greater trauma-related distress including PTSD. Yet social support could buffer the negative effects of psychosocial vulnerabilities on women’s health. METHODS/DESIGN: Mediation and moderated mediation models were tested with 371 inner-city women, including psychosocial vulnerability (i.e., catastrophizing, anger, social undermining) mediating the pathway between race and PTSD, and social support moderating psychosocial vulnerability and PTSD. RESULTS: Despite comparable rates of trauma, Black women reported higher vulnerability and PTSD symptoms, and lower support compared to White Hispanic and non-Hispanic women. Psychosocial vulnerability mediated the pathway between race and PTSD, and social support moderated vulnerability, reducing negative effects on PTSD. When examining associations by race, the moderation effect remained significant for Black women only. CONCLUSIONS: Altogether these psychosocial vulnerabilities represent one potential mechanism explaining Black women’s greater risk of PTSD, although cumulative psychosocial vulnerability may be buffered by social support. Despite higher support, inner-city White women’s psychosocial vulnerability may actually outweigh support’s benefits for reducing trauma-related distress.

We sought to determine whether women with overactive bladder who required third line therapy would demonstrate greater central sensitization, indexed by temporal summation to heat pain stimuli, than those with overactive bladder.We recruited 39 women with overactive bladder from the urology clinic who were planning to undergo interventional therapy for medication refractory overactive bladder with onabotulinumtoxinA bladder injection or sacral neuromodulation. We also recruited 55 women with overactive bladder who were newly seen at our urology clinic or who responded to advertisements for study participation. Participants underwent quantitative sensory testing using a thermal temporal summation protocol. The primary study outcome was the degree of temporal summation as reflected in the magnitude of positive slope of the line fit to the series of 10 stimuli at a 49C target temperature. We compared the degree of temporal summation between the study groups using linear regression.Women in the group undergoing third line therapy showed significantly higher standardized temporal summation slopes than those in the nontreatment group (β = 1.57, 95% CI 0.18-2.96, t = 2.25, p = 0.027). On exploratory analyses a history of incontinence surgery or hysterectomy was associated with significantly greater temporal summation.In this study the degree of temporal summation was elevated in women undergoing third line overactive bladder therapy compared to women with overactive bladder who were not undergoing that therapy. These findings suggest there may be pathophysiological differences, specifically in afferent nerve function and processing, in some women with overactive bladder.

Women may be disproportionately vulnerable to acute pain, potentially due to their social landscape. We examined whether positive and negative social processes (social support and social undermining) are associated with acute pain and if the processes are linked to pain via negative cognitive appraisal and emotion (pain catastrophizing, hyperarousal, anger). Psychosocial variables were assessed in inner-city women ( N = 375) presenting to an Emergency Department with acute pain. The latent cognitive-emotion variable fully mediated social undermining and support effects on pain, with undermining showing greater impact. Pain may be alleviated by limiting negative social interactions, mitigating risks of alternative pharmacological interventions.

Background: People with Alzheimer’s disease (AD) report pain less frequently and receive less pain medication than people without AD. Recent studies have begun to elucidate how pain may be altered in those with AD. However, potential sex differences in pain responsiveness have never been explored in these patients. It is unclear whether sex differences found in prior studies of healthy young and older individuals extend to people with AD. Objective: The purpose of this study was to examine sex differences in the psychophysical response to experimental thermal pain in people with AD. Methods: Cross-sectional analysis of 14 male and 14 female age-matched (≥65 years of age, median = 74) and AD severity-matched (Mini-Mental State Exam score 0.05). Conclusions: Results suggest experimental pain-related sex differences persist in older adults with AD in a different manner than those previously demonstrated in cognitively intact older adults. These findings could potentially aid in developing targeted pain management approaches in this vulnerable population. Further studies are warranted to replicate the findings from this pilot work.

Complex regional pain syndrome (CRPS) is a persistent pain condition that remains incompletely understood and challenging to treat. Historically, a wide range of different outcome measures have been used to capture the multidimensional nature of CRPS. This has been a significant limiting factor in the advancement of our understanding of the mechanisms and management of CRPS. In 2013, an international consortium of patients, clinicians, researchers, and industry representatives was established, to develop and agree on a minimum core set of standardised outcome measures for use in future CRPS clinical research, including but not limited to clinical trials within adult populations. The development of a core measurement set was informed through workshops and supplementary work, using an iterative consensus process. "What is the clinical presentation and course of CRPS, and what factors influence it?" was agreed as the most pertinent research question that our standardised set of patient-reported outcome measures should be selected to answer. The domains encompassing the key concepts necessary to answer the research question were agreed as follows: pain, disease severity, participation and physical function, emotional and psychological function, self-efficacy, catastrophizing, and patient's global impression of change. The final core measurement set included the optimum generic or condition-specific patient-reported questionnaire outcome measures, which captured the essence of each domain, and 1 clinician-reported outcome measure to capture the degree of severity of CRPS. The next step is to test the feasibility and acceptability of collecting outcome measure data using the core measurement set in the CRPS population internationally.

Objective Newborns requiring hospitalisation frequently undergo painful procedures. Prevention of pain in infants is of prime concern because of adverse associations with physiological and neurological development. However, pain mitigation is currently guided by behavioural observation assessments that have not been validated against direct evidence of pain processing in the brain. The aim of this study was to determine whether cry presence or amplitude is a valid indicator of pain processing in newborns. Design Prospective observational cohort. Setting Newborn nursery. Patients Healthy infants born at >37 weeks and Interventions We prospectively studied newborn cortical responses to light touch, cold and heel stick, and the amplitude of associated infant vocalisations using our previously published paradigms of time-locked electroencephalogram (EEG) with simultaneous audio recordings. Results Latencies of cortical peak responses to each of the three stimuli type were significantly different from each other. Of 54 infants, 13 (24%), 19 (35%) and 35 (65%) had cries in response to light touch, cold and heel stick, respectively. Cry in response to non-painful stimuli did not predict cry in response to heel stick. All infants with EEG data had measurable pain responses to heel stick, whether they cried or not. There was no association between presence or amplitude of cries and cortical nociceptive amplitudes. Conclusions In newborns with distinct brain responses to light touch, cold and pain, cry presence or amplitude characteristics do not provide adequate behavioural markers of pain signalling in the brain. New bedside assessments of newborn pain may need to be developed using brain-based methodologies as benchmarks in order to provide optimal pain mitigation.

Objective With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (e.g., pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain. Setting Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM). Methods As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions. Perspective The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Conclusions Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

OBJECTIVE: With the increasing societal awareness of the prevalence and impact of acute pain, there is a need to develop an acute pain classification system that both reflects contemporary mechanistic insights and helps guide future research and treatment. Existing classifications of acute pain conditions are limiting, with a predominant focus on the sensory experience (eg, pain intensity) and pharmacologic consumption. Consequently, there is a need to more broadly characterize and classify the multidimensional experience of acute pain.SETTING: Consensus report following expert panel involving the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), American Pain Society (APS), and American Academy of Pain Medicine (AAPM).METHODS: As a complement to a taxonomy recently developed for chronic pain, the ACTTION public-private partnership with the US Food and Drug Administration, the APS, and the AAPM convened a consensus meeting of experts to develop an acute pain taxonomy using prevailing evidence. Key issues pertaining to the distinct nature of acute pain are presented followed by the agreed-upon taxonomy. The ACTTION-APS-AAPM Acute Pain Taxonomy will include the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms. Future efforts will consist of working groups utilizing this taxonomy to develop diagnostic criteria for a comprehensive set of acute pain conditions.PERSPECTIVE: The ACTTION-APS-AAPM Acute Pain Taxonomy (AAAPT) is a multidimensional acute pain classification system designed to classify acute pain along the following dimensions: 1) core criteria, 2) common features, 3) modulating factors, 4) impact/functional consequences, and 5) putative pathophysiologic pain mechanisms.CONCLUSIONS: Significant numbers of patients still suffer from significant acute pain, despite the advent of modern multimodal analgesic strategies. Mismanaged acute pain has a broad societal impact as significant numbers of patients may progress to suffer from chronic pain. An acute pain taxonomy provides a much-needed standardization of clinical diagnostic criteria, which benefits clinical care, research, education, and public policy. For the purposes of the present taxonomy, acute pain is considered to last up to seven days, with prolongation to 30 days being common. The current understanding of acute pain mechanisms poorly differentiates between acute and chronic pain and is often insufficient to distinguish among many types of acute pain conditions. Given the usefulness of the AAPT multidimensional framework, the AAAPT undertook a similar approach to organizing various acute pain conditions.

Clinical diagnosis of complex regional pain syndrome (CRPS) is a dichotomous (yes/no) categorization, a format necessary for clinical decision making. Such dichotomous diagnostic categories do not convey an individual's subtle gradations in the severity of the condition over time and have poor statistical power when used as an outcome measure in research. This prospective, international, multicenter study slightly modified and further evaluated the validity of the CRPS Severity Score (CSS), a continuous index of CRPS severity. Using a prospective design, medical evaluations were conducted in 156 patients with CRPS to compare changes over time in CSS scores between patients initiating a new treatment program and patients on stable treatment regimens. New vs stable categorizations were supported by greater changes in pain and function in the former. Results indicated that CSS values in the stable CRPS treatment group exhibited much less change over time relative to the new treatment group, with intraclass correlations nearly twice as large in the former. A calculated smallest real difference value revealed that a change in the CSS of ≥4.9 scale points would indicate real differences in CRPS symptomatology (with 95% confidence). Across groups, larger changes in CRPS features on the CSS over time were associated in the expected direction with greater changes in pain intensity, fatigue, social functioning, ability to engage in physical roles, and general well-being. The overall pattern of findings further supports the validity of the CSS as a measure of CRPS severity and suggests it may prove useful in clinical monitoring and outcomes research.

BACKGROUND: It is currently unknown why people with Alzheimer’s disease (AD) receive less pain medication and report pain less frequently. OBJECTIVE: The purpose of this study was to determine the impact of AD on thermal psychophysics and resting-state functional connectivity (RSFC) among sensory, affective, descending modulatory, and default mode structures. METHODS: Controls (n = 23, 13 = female) and age-matched people with AD (n = 23, 13 = females) underwent psychophysical testing to rate perceptions of warmth, mild, and moderate pain and then completed resting-state fMRI. Between groups analysis in psychophysics and RSFC were conducted among pre-defined regions of interest implicated in sensory and affective dimensions of pain, descending pain modulation, and the default mode network. RESULTS: People with AD displayed higher thermal thresholds for warmth and mild pain but similar moderate pain thresholds to controls. No between-group differences were found for unpleasantness at any percept. Relative to controls, people with AD demonstrated reduced RSFC between the right posterior insula and left anterior cingulate and also between right amygdala and right secondary somatosensory cortex. Moderate pain unpleasantness reports were associated with increased RSFC between right dorsolateral prefrontal cortex and left ACC in controls only. CONCLUSIONS: While AD had little effect on unpleasantness, people with AD had increased thermal thresholds, altered RSFC, and no association of psychophysics with RSFC in pain regions. Findings begin to elucidate that in people with AD, altered integration of pain sensation, affect, and descending modulation may, in part, contribute to decreased verbal pain reports and thus decreased analgesic administration.

Chronic postsurgical pain impacts most amputees, with more than half experiencing neuralgic residual limb pain. The transition from normal acute postamputation pain to chronic residual limb pain likely involves both peripheral and central inflammatory mechanisms. As part of the Veterans Integrated Pain Evaluation Research study, we investigated links between systemic inflammatory mediator levels and chronic residual limb pain. Subjects included 36 recent active duty military traumatic amputees with chronic residual limb pain and 40 without clinically significant pain. Blood samples were obtained and plasma concentrations of an array of inflammatory mediators were analyzed. Residual limb pain intensity and pain catastrophizing were assessed to examine associations with inflammatory mediators. Pro-inflammatory mediators including tumor necrosis factor (TNF)-α, TNF-β, interleukin (IL)-8, ICAM-1, Tie2, CRP, and SAA were elevated in patients with chronic residual limb pain. Across all patients, residual limb pain intensity was associated positively with levels of several proinflammatory mediators (IL-8, TNF-α, IL-12, TNF-β, PIGF, Tie2, SAA, and ICAM-1), and inversely with concentrations of the anti-inflammatory mediator IL-13, as well as IL-2 and Eotaxin-3. Pain catastrophizing correlated positively with IL-8, IL-12, TNF-β, PIGF, and ICAM-1, and inversely with IL-13. Significant associations between catastrophizing and residual limb pain intensity were partially mediated by TNF-α, TNF- β, SAA, and ICAM-1 levels. Results suggest that chronic postamputation residual limb pain is associated with excessive inflammatory response to injury or to inadequate resolution of the postinjury inflammatory state. Impact of pain catastrophizing on residual limb pain may be because of part to common underlying inflammatory mechanisms.

Objective To examine psychophysical and brain activation patterns to innocuous and painful thermal stimulation along a continuum of healthy older adults. Design Single center, cross-sectional, within-subjects design. Methods Thermal perceptual psychophysics (warmth, mild, and moderate pain) were tested in 37 healthy older adults (65–97 years, median = 73 years). Percept thresholds (oC) and unpleasantness ratings (0–20 scale) were obtained and then applied during functional magnetic resonance imaging scanning. General linear modeling assessed effects of age on psychophysical results. Multiple linear regressions were used to test the main and interaction effects of brain activation against age and psychophysical reports. Specifically, differential age effects were examined by comparing percent-signal change slopes between those above/below age 73 (a median split). Results Advancing age was associated with greater thresholds for thermal perception (z = 2.09, P = 0.037), which was driven by age and warmth detection correlation (r = 0.33, P = 0.048). Greater warmth detection thresholds were associated with reduced hippocampal activation in “older” vs “younger” individuals (>/ 0.44, P Conclusions Advancing age may lead to altered thermal sensation and (in some circumstances) altered pain perception secondary to age-related changes in attention/novelty detection and cognitive functions.

Objective: Prescribed opioids for chronic pain management contribute significantly to the opioid crisis. There is a need to understand the real-world benefits that, despite risks, lead chronic pain patients to persist in opioid use. Negative reinforcement models of addiction posit that individuals use substances to reduce aversive states but have seldom been applied to prescribed opioids. Using ecological momentary assessment, we examined reciprocal associations between opioid use and physical pain, for which opioids are prescribed, and negative affect (NA), for which they are not. Method: Chronic low back pain patients on long-term opioid therapy (n = 34) without significant past-year opioid misuse reported multiple times daily via smartphone over 2 weeks (nobservations = 2,285). We hypothesized that pain and NA would be positively associated with subsequent opioid use, and that use would be negatively associated with subsequent pain and NA. Results: Time-lagged multilevel models indicated that participants were more likely to use opioids and in larger doses following elevated pain and NA. There was also an interaction of concurrent pain and NA on opioid dose. In turn, participants reported reduced pain and NA following larger doses. Additionally, individuals at high risk for opioid misuse, compared with low risk, took larger doses following pain, but also experienced smaller subsequent pain and NA reductions. Conclusions: Opioid use was bidirectionally associated with pain and NA. Findings fit negative reinforcement models associated with risk of developing opioid use disorder. Educating patients and providers about negative reinforcement may help reduce opioid use and opioid-associated risks. (PsycINFO Database Record (c) 2019 APA, all rights reserved)

Ethnic differences in pain response have been well documented, with non-Hispanic Black (NHB) participants reporting enhanced clinical pain and greater laboratory-evoked pain sensitivity to a variety of quantitative sensory testing (QST) methods compared to non-Hispanic Whites (NHW). One potential mechanism that may contribute to these disparities is differential functioning of endogenous pain-regulatory systems. To evaluate endogenous opioid (EO) mechanisms in pain responses, we examined group differences in response to tonic capsaicin pain following double-blinded crossover administration of saline and the opioid antagonist, naloxone. Ten percent topical capsaicin cream and a thermode were applied to the dorsum of the non-dominant hand, maintaining a constant temperature of 40°C for 90 min. Naloxone (0.1 mg/ kg) or saline placebo was administered at the 25 min mark and post-drug pain intensity ratings were obtained every 5 min thereafter. As an index of EO function, blockade effects were derived for each participant, reflecting the difference between mean post-drug pain intensity ratings under the saline versus naloxone conditions, with higher positive scores reflecting greater EO inhibition of pain. Thirty-nine healthy, young individuals (19 non-Hispanic Black [NHB], 20 non-Hispanic White [NHW]) participated. Group difference in EO function were identified, with NHB participants displaying lower EO function scores (mean=-10.8, SD=10.1) as compared to NHW participants (mean=-0.89, SD=11.5; p=0.038). NHB participants experienced significant paradoxical analgesia with naloxone. Thirty five percent of the NHW participants showed a positive blockade effect indicating EO analgesia (i.e., an increase in pain with naloxone), while only 10% of the NHB participants exhibited evidence of EO analgesia. These findings suggest differential functioning of the endogenous opioid pain regulatory system between NHB and NHW participants. Future research is warranted to examine whether these differences contribute to the disparities observed in clinical pain between groups.

Objectives Sleep disturbance and chronic pain are related. The present study evaluated both direct and indirect (mediated) pathways through which sleep disturbance might be related to chronic pain intensity and function. Methods In total, 87 individuals (64% female) with chronic low back pain but not using opioids daily completed questionnaires assessing their sleep disturbance, chronic pain intensity, function, depression, anxiety, positive affect, and catastrophizing. Results Greater sleep disturbance was associated with greater pain intensity, worse function, greater emotional distress, lower positive affect, and higher levels of catastrophizing. Cross-sectional mediation analyses revealed that the positive associations between sleep disturbance and chronic pain intensity were conveyed statistically not only by significant indirect effects of elevated emotional distress, lower positive affect, and greater catastrophizing associated with sleep disturbance, but also by significant direct effects of sleep disturbance on chronic pain intensity. Similarly, we found that the associations between sleep disturbance and impaired function were conveyed statistically not only by significant indirect effects of elevated chronic pain intensity associated with sleep disturbance, but also by significant direct effects of sleep disturbance on function. Discussion Sleep disturbance was related significantly with chronic pain intensity and function by both direct and indirect pathways. These results are consistent with an emerging literature highlighting the potential significance of sleep disturbance in chronic pain patients, and provide further support for addressing sleep disturbance in the assessment and management of chronic pain.

We sought to replicate previous findings that low endogenous opioid (EO) function predicts greater morphine analgesia and extended these findings by examining whether circulating endocannabinoids and related lipids moderate EO-related predictive effects. Individuals with chronic low-back pain (n = 46) provided blood samples for endocannabinoid analyses, then underwent separate identical laboratory sessions under 3 drug conditions: saline placebo, intravenous (i.v.) naloxone (opioid antagonist; 12-mg total), and i.v. morphine (0.09-mg/kg total). During each session, participants rated low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects 4 times in sequence after incremental drug dosing. Mean morphine effects (morphine-placebo difference) and opioid blockade effects (naloxone-placebo difference; to index EO function) for each primary outcome (low-back pain intensity, evoked heat pain intensity, and nonpain subjective effects) were derived by averaging across the 4 incremental doses. The association between EO function and morphine-induced back pain relief was significantly moderated by endocannabinoids [2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA)]. Lower EO function predicted greater morphine analgesia only for those with relatively lower endocannabinoids. Endocannabinoids also significantly moderated EO effects on morphine-related changes in visual analog scale-evoked pain intensity (2-AG), drug liking (AEA and 2-AG), and desire to take again (AEA and 2-AG). In the absence of significant interactions, lower EO function predicted significantly greater morphine analgesia (as in past work) and euphoria. Results indicate that EO effects on analgesic and subjective responses to opioid medications are greatest when endocannabinoid levels are low. These findings may help guide development of mechanism-based predictors for personalized pain medicine algorithms.

Chronic pain (CP) patients often display lower heart rate variability (HRV) and baroreceptor sensitivity (BRS), which are associated with increased evoked pain intensity and decreased pain tolerance.The purpose of this study was to test whether the association between low levels of HRV and BRS and increased evoked pain responsiveness in individuals with CP is mediated by psychological distress and whether this mediation is sex dependent.The sample consisted of 877 participants in Wave 6 of the Tromsø population study who reported clinically meaningful CP. Resting HRV and BRS parameters were derived from continuous beat-to-beat blood pressure recordings. Psychological distress was assessed using the Hopkins Symptom Checklist-10. After cardiovascular assessment, participants completed a 106-second cold pressor task (3°C bath), which assessed cold pressor pain intensity (CPI) and cold pressor pain tolerance (CPT).In the full CP sample, mediation analyses showed significant indirect effects, without direct effects, of HRV and BRS on both CPT and CPI via psychological distress. When stratified by sex, significant indirect effects via psychological distress were only found in males for the impact of rMSSD on CPT, the impact of SDNN on CPT, and the impact of BRS on CPT via psychological distress. Moderated mediation analyses revealed that there were no significant sex differences in the indirect effects of HRV and BRS on both CPT and CPI via psychological distress.The hypoalgesic impact of cardiovascular regulatory systems on evoked pain responses is conveyed via the indirect effects of psychological distress.

Use of opioid analgesics for management of chronic nonmalignant pain has become common, yet there are presently no well-validated predictors of optimal opioid analgesic efficacy. We examined whether psychosocial factors (eg, depressive symptoms) predicted changes in spontaneous low back pain after administration of opioid analgesics, and whether endogenous opioid (EO) function mediated these relationships. Participants with chronic low back pain but who were not chronic opioid users (N = 89) underwent assessment of low back pain intensity pre- and post-drug in 3 (counterbalanced) conditions: (1) placebo, (2) intravenous naloxone, and (3) intravenous morphine. Comparison of placebo condition changes in back pain intensity to those under naloxone and morphine provided indexes of EO function and opioid analgesic responses, respectively. Results showed that (1) most psychosocial variables were related significantly and positively to morphine analgesic responses for low back pain, (2) depressive symptoms, trait anxiety, pain catastrophizing, and pain disability were related negatively to EO function, and (3) EO function was related negatively to morphine analgesic responses for low back pain. Bootstrapped mediation analyses showed that links between morphine analgesic responses and depressive symptoms, trait anxiety, pain catastrophizing, and perceived disability were partially mediated by EO function. Results suggest that psychosocial factors predict elevated analgesic responses to opioid-based medications, and may serve as markers to identify individuals who benefit most from opioid therapy. Results also suggest that people with greater depressive symptoms, trait anxiety, pain catastrophizing, and perceived disability may have deficits in EO function, which may predict enhanced response to opioid analgesics.

The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks-American Pain Society Pain Taxonomy (AAPT) is designed to be an evidence-based multidimensional chronic pain classification system that will facilitate more comprehensive and consistent chronic pain diagnoses, and thereby enhance research, clinical communication, and ultimately patient care. Core diagnostic criteria (dimension 1) for individual chronic pain conditions included in the initial version of AAPT will be the focus of subsequent empirical research to evaluate and provide evidence for their reliability and validity. Challenges to validating diagnostic criteria in the absence of clear and identifiable pathophysiological mechanisms are described. Based in part on previous experience regarding the development of evidence-based diagnostic criteria for psychiatric disorders, headache, and specific chronic pain conditions (fibromyalgia, complex regional pain syndrome, temporomandibular disorders, pain associated with spinal cord injuries), several potential approaches for documentation of the reliability and validity of the AAPT diagnostic criteria are summarized. Perspective The AAPT is designed to be an evidence-based multidimensional chronic pain classification system. Conceptual and methodological issues related to demonstrating the reliability and validity of the proposed AAPT chronic pain diagnostic criteria are discussed.

A variety of approaches have been used to develop diagnostic criteria for chronic pain. The published evidence of the reliability and validity of existing diagnostic criteria is limited, and these criteria have typically not been used in clinical practice. The availability of a widely accepted, consistently applied, and evidence-based taxonomy of diagnostic criteria would improve the quality of clinical research on chronic pain and would be of great value in clinical practice. To address the need for evidence-based diagnostic criteria for the major chronic pain conditions, the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership with the US Food and Drug Administration and the American Pain Society (APS) have collaborated on the development of the ACTTION-APS Pain Taxonomy (AAPT). AAPT provides a multidimensional framework that is applied systematically in the development of diagnostic criteria. This article (1) describes the background and rationale for AAPT; (2) presents the AAPT taxonomy and the specific conditions for which diagnostic criteria have been developed (to be published separately); (3) briefly reviews the 5 dimensions that constitute the AAPT multidimensional framework and describes the 7 accompanying articles that discuss these dimensions and other important issues involving AAPT; and (4) provides an overview of next steps, specifically, the general processes by which the initial set of diagnostic criteria (for which the evidence base has been drawn from the literature, systematic reviews, and secondary analyses of existing databases) will undergo additional assessments of reliability and validity. Perspective To address the need for evidence-based diagnostic criteria for the major chronic pain conditions, the AAPT provides a multidimensional framework that is applied systematically in the development of diagnostic criteria. The long-term objective of AAPT is to advance the scientific understanding of chronic pain and its treatment.

Introduction This study sought to provide a preliminary assessment of whether spinally mediated afferent hyperactivity (i.e., central sensitization) might contribute to manifestations of overactive bladder syndrome (OAB) in women as indexed by elevated temporal summation of evoked heat pain stimuli. Methods We recruited 20 adult women with OAB who were planning to undergo interventional therapy for OAB with either onabotulinumtoxinA injection or sacral neuromodulation and 23 healthy controls without OAB symptoms to undergo quantitative sensory testing with cutaneous thermal pain temporal summation. The primary study outcome was the degree of temporal summation, as reflected in the magnitude of positive slope of the line fitted to the series of 10 stimuli at the 49°C target temperatures. Linear regression and analysis of covariance were utilized to compare the degree of temporal summation between study groups. Results The standardized slope of temporal summation trials for women with OAB was significantly higher than for controls (β = 3.43, 95% confidence interval = 0.6–6.2, P = 0.017). The adjusted means ±SE of the standardized temporal summation slopes for the full OAB and control groups were 3.0 ± 0.5 (95% confidence interval = 2.0, 4.1) and 1.7 ± 0.5 (95% confidence interval = 0.7, 2.7), respectively. Conclusion In this preliminary study, we demonstrated that women with OAB refractory to primary and secondary therapies exhibited greater thermal cutaneous temporal summation than women without OAB symptoms. This suggests that central sensitization, indexed by temporal summation, may be an underlying factor contributing to OAB in some women. Neurourol. Urodynam. © 2016 Wiley Periodicals, Inc.

Functional abdominal pain (FAP) is associated with enhanced pain responsiveness. Although impaired conditioned pain modulation (CPM) characterizes adults with a variety of chronic pain conditions, relatively little is known about CPM in youth with FAP. This study assessed CPM to evoked thermal pain in 140 youth (ages 10-17), 63 of whom had FAP and 77 of whom were healthy controls. Multilevel models demonstrated weaker CPM effects in youth with FAP than in healthy youth, as evident in slower within-person decreases in pain ratings during the conditioning phase. Weaker CPM effects were associated with greater somatic symptom severity and functional disability. Pain responses in youth with FAP were heterogeneous, with 43% of youth showing an unexpected increase in pain ratings during the conditioning phase, suggesting sensitization rather than CPM-related pain inhibition. These findings highlight directions for future research on the emergence and maintenance of FAP in youth.

Mechanisms underlying pain perception and afferent hypersensitivity, such as central sensitization, may impact overactive bladder (OAB) symptoms. However, little is known about associations between OAB symptom severity, pain experience, and presence of comorbid chronic pain syndromes. This study examined relationships between OAB symptoms, somatic symptoms, and specific chronic pain conditions in which central sensitization is believed to play a primary role, in a community-based sample of adult women with OAB.We recruited adult women with OAB to complete questionnaires assessing urinary symptoms, pain and somatic symptoms, and preexisting diagnoses of central sensitivity syndromes. We analyzed the effects of overall bodily pain intensity, general somatic symptoms, and diagnoses of central sensitivity syndromes on OAB symptom bother and health-related quality of life.Of the 116 women in this study, over half (54%) stated their urge to urinate was associated with pain, pressure, or discomfort. Participants reported a wide range of OAB symptoms and health-related quality of life. There was a significant, positive correlation between OAB symptoms and somatic symptoms as well as overall pain intensity. Only 7% of women met diagnostic criteria for fibromyalgia; yet these women demonstrated significantly increased OAB symptom burden and decreased OAB quality of life compared to those without fibromyalgia.Women with more severe OAB symptoms reported increased general somatic symptom burden and increased overall body pain intensity, especially women with fibromyalgia. These findings suggest that attributes of pain and co-morbidity with chronic pain conditions may impact the experience of OAB symptoms for many women. Neurourol. Urodynam. 36:1113-1118, 2017. © 2016 Wiley Periodicals, Inc.

The pathophysiological mechanisms underlying overactive bladder syndrome (OAB) can include dysfunction of sensory pathways of the peripheral and central nervous systems, resulting in bladder hypersensitivity. Central sensitization describes an induced state of spinal hypersensitivity that is associated with a variety of chronic pain disorders that share many attributes with OAB, albeit without the presence of pain. As such, the concept of central sensitization might be relevant to understanding the mechanisms and clinical manifestations of OAB syndrome. An understanding of the pathophysiology and clinical manifestations of central sensitization, and the evidence that supports a role of central sensitization in OAB, including the potential implications of mechanisms of central sensitization for the treatment of patients with OAB could provide a novel approach to the treatment of patients with this disease. Such an approach would be especially relevant to those patients with central sensitization-related comorbidities, and has the potential to improve the outcomes of these patients in particular.

Recent studies suggest that participant expectations influence pain ratings during conditioned pain modulation testing. The present study extends this work by examining expectancy effects among individuals with and without chronic back pain after administration of placebo, naloxone, or morphine. This study aims to identify the influence of individual differences in expectancy on changes in heat pain ratings obtained before, during, and after a forearm ischemic pain stimulus. Participants with chronic low back pain (n = 88) and healthy controls (n = 100) rated heat pain experience (i.e., “test stimulus”) before, during, and after exposure to ischemic pain (i.e., “conditioning stimulus”). Prior to testing, participants indicated whether they anticipated that their heat pain would increase, decrease, or remain unchanged during ischemic pain. Analysis of the effects of expectancy (pain increase, decrease, or no change), drug (placebo, naloxone, or morphine), and group (back pain, healthy) on changes in heat pain revealed a significant main effect of expectancy (p = 0.001), but no other significant main effects or interactions. Follow-up analyses revealed that individuals who expected lower pain during ischemia reported significantly larger decreases in heat pain as compared with those who expected either no change (p = 0.004) or increased pain (p = 0.001). The present findings confirm that expectancy is an important contributor to conditioned pain modulation effects, and therefore significant caution is needed when interpreting findings that do not account for this individual difference. Opioid mechanisms do not appear to be involved in these expectancy effects.

OBJECTIVE This study examined the diagnostic accuracy and test-retest reliability of a novel dynamic evoked pain protocol (slowly repeated evoked pain [SREP]) compared with temporal summation of pain (TSP), a standard index of central sensitization. METHODS Thirty-five fibromyalgia (FM) patients and 30 rheumatoid arthritis (RA) patients completed, in pseudorandomized order, a standard mechanical TSP protocol (10 stimuli of 1-second duration at the thenar eminence using a 300-g monofilament with 1 second interstimulus interval) and the SREP protocol (9 suprathreshold pressure stimuli of 5-second duration applied to the fingernail with a 30-second interstimulus interval). To evaluate reliability for both protocols, they were repeated in a second session 4-7 days later. RESULTS Evidence for significant pain sensitization over trials (increasing pain intensity ratings) was observed for SREP in FM (p < .001) but not in RA (p = .35), whereas significant sensitization was observed in both diagnostic groups for the TSP protocol (p < .008). Compared with TSP, SREP demonstrated higher overall diagnostic accuracy (87.7% versus 64.6%), greater sensitivity (0.89 versus 0.57), and greater specificity (0.87 versus 0.73) in discriminating between FM and RA patients. Test-retest reliability of SREP sensitization was good in FM (intraclass correlations = 0.80), and moderate in RA (intraclass correlations = 0.68). CONCLUSIONS SREP seems to be a dynamic evoked pain index tapping into pain sensitization that allows for greater diagnostic accuracy in identifying FM patients compared with a standard TSP protocol. Further research is needed to study mechanisms underlying SREP and the potential utility of adding SREP to standard pain evaluation protocols.

BACKGROUND Given high levels of traumatic stress for low-income, inner-city women, investigating the link between posttraumatic stress disorder (PTSD) and pain is especially important. PURPOSE Using the conservation of resources theory, we investigated direct and indirect relationships of PTSD symptoms, vulnerability factors (ie, resource loss, depressive symptoms, and social undermining), and resilience factors (ie, optimism, engagement, and social support) to acute pain reports in a sample of low-income, inner-city women. METHODS Participants (N=341; mean age=28 y; 58.0% African American) were recruited from an inner-city Emergency Department following presentation with acute pain. Study data were gathered from psychosocial questionnaires completed at a baseline interview. RESULTS Structural equation modeling examined direct and indirect relationships among PTSD symptoms, vulnerability factors, and resilience factors on self-reported pain intensity and pain interference. PTSD symptoms were directly related to higher pain intensity and pain interference and indirectly related through positive associations with vulnerability factors (all Ps

Introduction Resting blood pressure (BP) has been found to be inversely associated with evoked pain responsiveness in healthy populations. However, some reports suggest that BP-related pain modulation may be dysfunctional in chronic pain patients. This study examined whether BP-related pain modulation, indexed by both static and dynamic evoked pain responses, is altered in fibromyalgia (FM) patients compared to pain-free individuals. Method Pain threshold and tolerance as static evoked pain measures and slowly repeated evoked pain (SREP) as a dynamic evoked pain index were measured in 30 FM patients and 27 healthy controls. BP was continuously recorded throughout a 5 minute pre-pain rest period. Results SREP sensitization was observed only in the FM group. Higher BP predicted elevated pain threshold and tolerance in healthy individuals, but not in FM. Conversely, BP was inversely associated with SREP sensitization in FM whereas no association was found in healthy controls. Conclusions Static evoked pain measures suggested BP-related pain inhibitory dysfunction in FM. In contrast, for pain sensitization as indexed by SREP, FM displayed the expected BP-related inhibitory effects. BP-related pain modulation is manifested in FM differentially for static versus dynamic pain indicators. Use of both types of evoked pain measures may be valuable in the study of mechanisms underlying altered pain modulatory systems in FM.

BACKGROUND: In healthy individuals, elevated resting blood pressure (BP) is associated with reduced pain responsiveness and lower temporal summation. Prior work indicates that this BP-related hypoalgesia is reduced in individuals with chronic pain. PURPOSE: This study evaluated whether resolution of chronic pain was associated with greater BP-related hypoalgesia compared to nonresolution. METHODS: From a prospective sample of adolescents and young adults diagnosed with chronic functional abdominal pain an average of 9 years earlier, 99 individuals in whom the condition had resolved and 51 individuals with ongoing abdominal pain were studied. Resting systolic BP was assessed, followed by evaluation of thermal pain threshold and tolerance, and assessment of temporal summation to thermal pain stimuli. RESULTS: Higher resting systolic BP was significantly associated with higher pain threshold and tolerance, and lower temporal summation only in the group with resolved functional abdominal pain (p < .05). Hierarchical regressions revealed that interactions between BP and resolution of chronic pain were significant only for pain tolerance (p < .05). Analyses by sex indicated that interactions between BP and resolution status were significant for the temporal summation outcome in males but not in females. CONCLUSIONS: Results suggest that BP-related hypoalgesic mechanisms may be more effective in individuals in whom chronic pain has resolved compared to those with ongoing chronic pain. Findings hint at sex differences in the extent to which resolution of chronic pain is associated with BP-related hypoalgesia. Whether greater BP-related hypoalgesia is a consequence of, or alternatively a contributor to, resolution of chronic pain warrants further investigation.

Peripheral neuropathic pain is among the most prevalent types of neuropathic pain. No comprehensive peripheral neuropathic pain classification system that incorporates contemporary clinical, diagnostic, biological, and psychological information exists. To address this need, this article covers the taxonomy for 4 focal or segmental peripheral neuropathic pain disorders, as part of the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership and the American Pain Society (APS) collaborative to develop a standardized, evidence-based taxonomy initiative: the ACTTION-APS Pain Taxonomy (AAPT). The disorders—postherpetic neuralgia, persistent posttraumatic neuropathic pain, complex regional pain disorder, and trigeminal neuralgia—were selected because of their clinical and clinical research relevance. The multidimensional features of the taxonomy are suitable for clinical trials and can also facilitate hypothesis-driven case-control and cohort epidemiologic studies. Perspective The AAPT peripheral neuropathic pain taxonomy subdivides the peripheral neuropathic pain disorders into those that are generalized and symmetric and those that are focal or segmental and asymmetric. In this article, we cover the focal and segmental disorders: postherpetic neuralgia, persistent posttraumatic neuropathic pain, complex regional pain disorder, and trigeminal neuralgia. The taxonomy is evidence-based and multidimensional, with the following dimensions: 1) core diagnostic criteria; 2) common features; 3) common medical and psychiatric comorbidities; 4) neurobiological, psychosocial, and functional consequences; and 5) putative neurobiological and psychosocial mechanisms, risk factors, and protective factors.

Race and ethnicity shape the experience of pain in adults. African Americans typically exhibit greater pain intensity and evoked pain responsiveness than non-Hispanic whites. However, it remains unclear whether there are racial differences in conditioned pain modulation (CPM) and if these are present in youth. CPM refers to a reduction in perceived pain intensity for a test stimulus during application of a conditioning stimulus and may be especially relevant in determining risk for chronic pain. The present study assessed CPM to evoked thermal pain in 78 healthy youth (ages 10–17 years), 51% of whom were African American and 49% of whom were non-Hispanic white. African American youth reported lower mean conditioning pain ratings than non-Hispanic white youth, controlling for mean preconditioning pain ratings, which is consistent with stronger CPM. Multilevel models demonstrated stronger CPM effects in African American than non-Hispanic white youth, as evident in more rapid within-person decreases in pain ratings during the conditioning phase. These findings suggest that diminished CPM likely does not account for the enhanced responsiveness to evoked thermal pain observed in African American youth. These results may have implications for understanding racial differences in chronic pain experienced in adulthood. Perspective This study evaluated conditioned pain modulation to evoked thermal pain in African American and non-Hispanic white youth. Findings could have implications for the development of personalized chronic pain treatment strategies that are informed by race and ethnicity.

Individuals with functional gastrointestinal disorders (FGIDs) report experiencing trauma more often than healthy controls, but little is known regarding psychophysical correlates.The purpose of this study was to test the hypothesis that adolescents and young adults with FGIDs since childhood and a trauma history (n = 38) would exhibit heightened temporal summation to thermal pain stimuli, an index of central sensitization, and greater clinical symptoms compared to patients with FGIDs and no trauma history (n = 95) and healthy controls (n = 135).Participants completed self-report measures, an experimental pain protocol, and psychiatric diagnostic interview as part of a larger longitudinal study.FGID + Trauma patients exhibited greater temporal summation than FGID + No Trauma patients and healthy controls. Additionally, FGID + Trauma patients exhibited greater gastrointestinal and non-gastrointestinal symptom severity, number of chronic pain sites, and disability.Assessing for trauma history in patients with FGIDs could identify a subset at risk for greater central sensitization and pain-related symptoms.

Racial differences in pain responsiveness have been demonstrated in adults. However, it is unclear whether racial differences are also present in youth and whether they extend to experimental pain indices assessing temporal summation of second pain (TSSP). Temporal summation of second pain provides an index of pain sensitivity and may be especially relevant in determining risk for chronic pain. This study assessed pain tolerance and TSSP to evoked thermal pain in 78 healthy youth (age range, 10-17), 51% of whom were African American and 49% were non-Hispanic white. Multilevel models revealed within-individual increases in pain ratings during the temporal summation task in non-Hispanic white youth that were consistent with TSSP. Pain ratings did not change significantly during the temporal summation task in African-American youth. Baseline evoked pain ratings were significantly higher in African-American compared with non-Hispanic white youth. These findings suggest that enhanced responsiveness to evoked thermal pain in African Americans is present in adolescence but is unlikely to be related to elevated TSSP. These results may have implications for understanding racial differences in chronic pain experience in adulthood.

For people with chronic pain, anger-related factors are significantly associated with pain intensity, mood and physical function such that greater anger is related to poorer adjustment (Janssen, Spinhoven, & Brosschot, 2001; Kerns, Rosenberg, & Jacob, 1994; Nicholson, Gramling, Ong, & Buenevar, 2003; Wade, Price, Hamer, Schwartz & Hart, 1990). Evidence suggests that how anger is regulated – expression, inhibition – may have greater consequences for chronic pain patients’ pain and function than their level of state anger (Bruehl, Chung, & Burns, 2006; Bruehl, Burns, Chung, Ward, & Johnson, 2002; Burns et al., 2008). Anger expression may be related to pain and function along at least two pathways. First, it has been proposed that people who tend to verbally or physically express anger and who exhibit high pain sensitivity may be characterized by deficits in endogenous inhibitory mechanisms (Bruehl et al., 2002). Findings support this model and indicate that chronic pain patients and healthy people alike who are high in trait anger-expressiveness show evidence of deficient endogenous opioid function, thus leaving them with elevated pain sensitivity (Bruehl et al., 2002). Second, a symptom-specific reactivity model (Flor, Turk & Birbaumer, 1985) has been adapted for anger and chronic pain, and holds that anger arousal may lead to increases in muscle tension near the site of injury, and thereby increase pain (Burns, Bruehl, & Quartana, 2006). In the case of chronic low back pain (CLBP) patients, the relevant muscles would be in the low back (e.g., lower paraspinal [LP] muscles). Results support this model, and indicate that anger arousal among CLBP patients produces greater increases in LP muscle tension than sadness (Burns, 2006), and that CLBP patients with elevated trait anger-expressiveness showed greater increases in LP muscle tension during anger arousal than those low in trait anger-expressiveness (Burns et al., 2006). Anger inhibition may be related to pain and function also along at least two pathways. First, a thought suppression model (Wegner, 1994) was adapted for anger inhibition and pain, and holds that inhibiting anger has the ironic consequence of amplifying and maintaining anger which in turn exerts delayed negative effects on responses to later events (Burns, Quartana, & Bruehl, 2008). Thus, inhibiting anger can worsen later pain perception as ironically sustained thoughts of anger contaminate the experience of pain. Results support this model in that chronic pain patients and healthy people who inhibited anger during anger arousal showed greater increases in anger during anger-induction and reported greater anger and pain intensity during subsequent acute pain-induction than those who did not inhibit anger during anger arousal (Burns, 2008; Quartana & Burns 2007). Second, the symptom-specific reactivity model may also apply to anger inhibition. Findings showed that CLBP patients evinced greater increases in LP muscle tension while inhibiting anger during anger arousal than those not inhibiting, and these increases were shown to predict the frequency of observable pain behaviors during subsequent pain induction (Burns, Quartana, Gilliam, Matsuura, Nappi, & Wolfe, 2012). These conceptual models support hypotheses that both anger expression and inhibition can lead to increased pain sensitivity and intensity, and may do so via distinct pathways. Findings from numerous cross-sectional questionnaire and lab-based studies support these contentions (Bruehl et al., 2006; Burns et al., 2008). However, the questionnaire studies based on traits tell us little about the effects of actual anger regulation behaviors on pain and functioning, and although some lab-based studies did manipulate anger arousal, anger regulation behavior and pain in controlled conditions, ecological validity is limited by the artificial nature of the procedures. Thus, we know little about relationships between what people actually do in everyday life to regulate anger and their pain and function. Results of two recent daily diary studies help address this shortcoming. In the first study (van Middendorp, Lumley, Moerbeek, Jacobs, Bijlsma, & Geenen, 2010), results suggested that behavioral anger expression during an anger-provoking event during the day was related to elevated end-of-day pain. They also reported that state anger was related to higher end-of-day pain. This design did not include true lagged analyses, so it is not clear whether anger predicted pain or vice versa. In the second study (Bruehl, Liu, Burns, Chont, & Jamison, 2012), results of lagged analyses suggested that behavioral anger expression during one period was related to elevated pain in the subsequent period, providing the first evidence of a longitudinal effect. Their assessment was limited, however, only to anger expression and patient rated pain intensity, and, moreover, did not include state anger. In the present study, we used electronic diary methods to replicate and extend prior work, and evaluate the degree to which patient feelings of anger and behavioral anger regulation – both expression and inhibition – occurring in the course of daily life was related to both patient pain and function as rated by patients. In addition, these data were collected as part of a larger study that also included spouse ratings of patient pain and function (Burns et al., in press). Specifically, patients with chronic low back pain (CLBP) and their spouses completed electronic diary entries 5 times/day for 14 days using Personal Data Assistants (PDAs). On one level, if anger arousal and/or behavioral anger regulation, as it occurs in everyday life, are related to pain and function, then concurrent analyses would show relationships between increases in state anger, anger expression and/or inhibition and fluctuations in pain and function. Further, if anger arousal and/or behavioral anger regulation actually influence pain and function, then lagged analyses would show that initial increases in state anger, anger expression and/or inhibition predict later fluctuations in pain and function, particularly in the case of anger inhibition given prior evidence of delayed effects on pain (Burns et al. 2008) (i.e., anger → pain). Alternatively, it may be the case, as suggested by results of Feldman, Downey and Schiffer-Neitz (1999), that initial pain intensity could predispose someone to experience later anger and the need to regulate it, and thus initial increases in pain would predict later fluctuations in anger arousal, anger expression and/or inhibition (i.e., pain → anger). On another level, if increases in anger arousal, anger expression and/or inhibition are indeed related to changes in patient pain and function, these increases should be related to demonstrable pain and function changes that can be observed by reporters other than the patient. We hypothesized that patient-reported increases in their anger arousal, behavioral anger expression and/or inhibition would be related to spouse ratings of observable patient behavior. Finally, the need to regulate anger presupposes the presence of anger arousal. If patient behavioral anger regulation per se is a key phenomenon related to current and later pain and function, then anger regulation factors should exert unique effects beyond those attributable to anger arousal alone. To address this issue, we controlled for either concurrent state anger or lagged state anger where relevant. Note that because anger arousal is a core and necessary constituent of the phenomenon “anger regulation,” statistically controlling for state anger represents a conservative and stringent approach.

Chronic pain is associated with elevated negative emotions, and resources needed to adaptively regulate these emotions can be depleted during prolonged pain. Studies of links between pain, function, and negative emotions in people with chronic pain, however, have focused almost exclusively on relationships among mean levels of these factors. Indexes that may reflect aspects of emotion regulation have typically not been analyzed. We propose that 1 index of emotion regulation is variability in emotion over time as opposed to average emotion over time. The sample was 105 people with chronic low back pain and 105 of their pain-free spouses. They completed electronic diary measures 5x/d for 14 consecutive days, producing 70 observations per person from which we derived estimates of within-subject variance in negative emotions. Location-scale models were used to simultaneously model predictors of both mean level and variance in patient negative emotions over time. Patients reported significantly more variability in negative emotions compared to their spouses. Patients who reported higher average levels of pain, pain interference, and downtime reported significantly higher levels of variability in negative emotions. Spouse-observed pain and pain behaviors were also associated with greater variability in patients' negative emotions. Test of the inverse associations between negative emotion level and variability in pain and function were significant but weaker in magnitude. These findings support the notion that chronic pain may erode negative emotion regulation resources, to the potential detriment of intra- and inter-personal function.

Having a parent with chronic pain (CP) may confer greater risk of persistence of CP from childhood into young adulthood. Social learning, such as parental modeling and reinforcement, represents one plausible mechanism for the transmission of risk of CP from parents to offspring. Based on a 7-day pain diary in 154 pediatric patients with functional abdominal CP, we tested a model in which parental CP predicted adolescents' daily average CP severity and functional impairment (distal outcomes) via parental modeling of pain behaviors and parental reinforcement of adolescent's pain behaviors (mediators) and adolescents' cognitive appraisals of pain threat (proximal outcome representing adolescents' encoding of parents' behaviors). Results indicated significant indirect pathways from parental CP status to adolescent average daily pain severity (b = 0.18, SE = 0.08, 95% confidence interval: 0.04-0.31, P = 0.03) and functional impairment (b = 0.08, SE = 0.04, 95% confidence interval: 0.02-0.15, P = 0.03) over the 7-day diary period via adolescents' observations of parent pain behaviors and adolescent pain threat appraisal. The indirect pathway through parental reinforcing responses to adolescents' pain did not reach significance for either adolescent pain severity or functional impairment. Identifying mechanisms of increased risk of pain and functional impairment in children of parents with CP ultimately could lead to targeted interventions aimed at improving functioning and quality of life in families with CP. Parental modeling of pain behaviors represents a potentially promising target for family-based interventions to ameliorate pediatric CP.

Considerable research links chronic pain to autonomic nervous system (ANS) dysfunction, specifically low heart rate variability (HRV) mediated by reduced parasympathetic activity. However, little is known about factors that influence ANS function in chronic pain. The ANS is the primary pathway for brain-gut communication, making it of particular interest in gastrointestinal disorders, such as irritable bowel syndrome, characterized by functional abdominal pain (FAP). We evaluated the relation of sex, pain severity, and psychological stress to ANS function in adolescents/young adults from a database of pediatric FAP and control participants enrolled 8 years earlier in a prospective study of pain. At follow-up in adolescence/young adulthood (Mean age = 19.46, SD = 3.48), we classified participants as Pain-Remit (n = 130), Pain-Persist (n = 96), and pain-free controls (n = 123). We recorded electrocardiogram data at rest and during laboratory stressors. Results demonstrated significantly lower HRV in Pain-Persist females compared with Pain-Remit females, female controls, and all males regardless of pain category. Spectral analysis of electrocardiogram showed that Pain-Persist females had reduced power in the high frequency domain of cardiac activity, ie, reduced parasympathetic "braking" of sympathetic activity, both at rest and during stress. Pain-Remit females exhibited levels of autonomic imbalance intermediate between those of females with persistent FAP and all other participants. Parasympathetically mediated low HRV in young women with persistent FAP may reflect a peripheral mechanism (eg, gut dysfunction) or a central nervous system mechanism (eg, pain amplification or poor emotion self-regulation) involving prolonged sympathetic activation.

Objective A long-standing hypothesis is that when compared with males, females may be at increased risk of experiencing greater pain sensitivity and unpleasantness. The purpose of this study was to examine sex differences in pain psychophysics and resting state functional connectivity (RSFC) in core pain regions in an age- and sex-matched sample of healthy older adults. Design Between groups, cross-sectional. Setting Vanderbilt University and Medical Center. Subjects The sample in the analyses reported here consisted of 19 cognitively intact males matched with 19 cognitively intact females of similar ages (median ages: females = 70 years, males = 68 years). Methods Psychophysical assessment of experimental thermal pain and RSFC. Results There were no significant differences in perceptual thresholds or unpleasantness ratings in response to thermal stimuli. Older males showed greater RSFC between the affective and sensory networks and between affective and descending modulatory networks. Conversely, older females showed greater RSFC between the descending modulatory network and both sensory and affective networks. The strongest evidence for sex differences emerged in the associations of thermal pain with RSFC between the anterior cingulate cortex (ACC) and amygdala and between the ACC and periaqueductal gray matter in older females relative to older males. Conclusions We found no differences in pain sensitivity or pain affect between older males and older females. Additionally, we found that older females exhibited a greater association between thermal pain sensitivity and RSFC signal between regions typically associated with pain affect and the descending modulatory system. One interpretation of these findings is that older females may better engage the descending pain modulatory system. This better engagement possibly translates into older females having similar perceptual thresholds for temperature sensitivity and unpleasantness associated with mild and moderate pain. These findings contrast with studies demonstrating that younger females find thermal pain more sensitive and more unpleasant.

Objective The pathophysiology of fibromyalgia has been related to central pain sensitization. This study tested a laboratory protocol evaluating responses to slowly repeated evoked pain stimuli (SREP) that may index central pain sensitization in fibromyalgia. Design A between-subjects controlled laboratory study. Subjects Twenty-four fibromyalgia patients and 24 healthy participants. Methods A SREP protocol was administered to all subjects, consisting of a single series of nine low-intensity pressure stimuli of five-second duration and thirty-second interstimulus interval. Subjective evoked pain intensity was assessed with a visual analogical scale. Clinical fibromyalgia pain was assessed with the McGill Pain Questionnaire. Results Perceived pain intensity increased during the SREP protocol in fibromyalgia patients but not in healthy participants. Neither pain threshold nor pain tolerance was associated with SREP. Degree of SREP sensitization was associated with McGill Pain Questionnaire-Sensory ratings of fibromyalgia pain. The effect size for differences between the fibromyalgia and healthy control groups was greater, and the overlaps of the groups distributions lower, for SREP sensitization than for traditional evoked pain measures of pain threshold and tolerance. SREP demonstrated higher specificity in discriminating fibromyalgia and control groups relative to pain threshold or tolerance. Conclusions A protocol employing a single series of nine low-suprathreshold-intensity slowly repeated pain stimuli elicits increased perceived pain in fibromyalgia patients, consistent with central sensitization despite relatively long interstimulus intervals. SREP appears to be more useful than traditional evoked pain threshold tolerance measures in terms of predicting levels of clinical pain and discriminating between fibromyalgia patients and healthy individuals.

Long-term use of opioid analgesics may be ineffective or associated with significant negative side effects for some people. At present, there is no sound method of identifying optimal opioid candidates. Individuals with chronic low back pain (n = 89) and healthy control individuals (n = 102) underwent ischemic pain induction with placebo, opioid blockade (naloxone), and morphine in counterbalanced order. They completed the Spielberger Anger-Out subscale. Endogenous opioid function × Anger-out × Pain status (chronic pain, healthy control) interactions were tested for morphine responses to ischemic threshold, tolerance, and pain intensity (McGill Sensory and Affective subscales) and side effects. For individuals with chronic pain and healthy control participants, those with low endogenous opioid function and low anger-out scores exhibited the largest morphine analgesic responses, whereas those with high anger-out and low endogenous opioid function showed relatively weaker morphine analgesic responses. Further, individuals with chronic pain with low endogenous opioid function and low anger-out scores also reported the fewest negative effects to morphine, whereas those with low endogenous opioid function and high anger-out reported the most. Findings point toward individuals with chronic pain who may strike a favorable balance of good analgesia with few side effects, as well as those who have an unfavorable balance of poor analgesia and many side effects. Perspective We sought to identify optimal candidates for opioid pain management. Low back pain patients who express anger and also have deficient endogenous opioid function may be poor candidates for opioid therapy. In contrast, low back patients who tend not to express anger and who also have deficient endogenous opioid function may make optimal candidates for opioid therapy.