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Supplemental Digital Content is Available in the Text. Weather sensitivity among patients with chronic pain is a phenomenon more apparent in some participant subgroups., Introduction: Previous studies on the association between weather and pain severity among patients with chronic pain have produced mixed results. In part, this inconsistency may be due to differences in individual pain responses to the weather. Methods: To test the hypothesis that there might be subgroups of participants with different pain responses to different weather conditions, we examined data from a longitudinal smartphone-based study, Cloudy with a Chance of Pain, conducted between January 2016 and April 2017. The study recruited more than 13,000 participants and recorded daily pain severity on a 5-point scale (range: no pain to very severe pain) along with hourly local weather data for up to 15 months. We used a Bayesian multilevel model to examine the weather–pain association. Results: We found 1 in 10 patients with chronic pain were sensitive to the temperature, 1 in 25 to relative humidity, 1 in 50 to pressure, and 3 in 100 to wind speed, after adjusting for age, sex, belief in the weather–pain association, mood, and activity level. The direction of the weather–pain association differed between people. Although participants seem to be differentially sensitive to weather conditions, there is no definite indication that participants' underlying pain conditions play a role in weather sensitivity. Conclusion: This study demonstrated that weather sensitivity among patients with chronic pain is more apparent in some subgroups of participants. In addition, among those sensitive to the weather, the direction of the weather–pain association can differ.

Supplemental Digital Content is Available in the Text. The University of Toronto Interfaculty Pain Curriculum has significantly improved students' pain knowledge and ability to develop interprofessional care plans over the period 2009 to 2019., Introduction: Delivery of interprofessional pain education for prelicensure healthcare professionals is strongly recommended to advance a workforce ready for collaborative practice and to improve the quality and outcomes of pain care. Objectives: We report a 10-year (2009–2019) longitudinal evaluation of a 20-hour undergraduate Interfaculty Pain Curriculum (IPC) delivered to students in the Faculties of Dentistry, Nursing, Pharmacy, and Medicine (also including the Departments of Physical Therapy, Occupational Therapy and Physician Assistant) at the University of Toronto, Canada. The IPC follows a constructivist approach to facilitate interactive and multifaceted learning. Methods: Evaluation methods based on the Kirkpatrick model were used to appraise changes in participating students' pain knowledge and beliefs and their ability to collaboratively develop an interprofessional pain management plan. Results: A total of 10,693 students participated over the 10-year study period. The mean annual attendance was 972 students and participation to the program increased significantly over the years. Overall, the IPC was effective in improving students' mean pain knowledge and beliefs scores; however, the mean knowledge score gains were negatively correlated with time, likely related to increased uniprofessional pain education. Although an increasing trend in mean interprofessional pain management plan scores was observed, the scores were not significantly correlated with time. Conclusions: The interactive and multifaceted IPC is consistently effective in improving knowledge and beliefs and interprofessional pain management care plan development among participating student cohorts. Future inquiry is required to better understand the mechanisms behind student learning in interprofessional pain education to enhance pain curriculum development and delivery.

Lower levels of physical activity in the first month after mild TBI predicts decreased conditioned pain modulation and greater pain catastrophizing in patients with mild TBI., Objective: The purpose of this study was to determine whether self-reported physical activity (PA) in the first month after mild traumatic brain injury (mTBI) predicts endogenous pain modulatory function and pain catastrophizing at 1 to 2 weeks and 1 month after injury in patients with mTBI. Methods: Patients with mild traumatic brain injury completed study sessions at 1 to 2 weeks and 1 month after injury. Assessments included a headache survey, Pain Catastrophizing Scale, International Physical Activity Questionnaire-Short Form, and several quantitative sensory tests to measure endogenous pain modulatory function including conditioned pain modulation (CPM), temporal summation, and pressure pain thresholds of the head. Hierarchical linear regressions determined the relationship between the PA variables (predictors) and pain catastrophizing and pain modulation variables (dependent variables) cross-sectionally and longitudinally, while controlling for potential covariates. Results: In separate hierarchical regression models, moderate PA, walking, and total PA at 1 to 2 weeks after injury predicted pain inhibition on the CPM test at 1 month, after controlling for significant covariates. In addition, a separate regression revealed that minutes sitting at 1 month predicted CPM at 1 month. Regarding predicting pain catastrophizing, the regression results showed that sitting at 1 to 2 weeks after injury significantly predicted pain catastrophizing at 1 month after injury. Conclusion: Greater self-reported PA, especially moderate PA, 1 to 2 weeks after injury longitudinally predicted greater pain inhibitory capacity on the CPM test at 1 month after injury in patients with mTBI. In addition, greater sedentary behavior was associated with worse pain inhibition on the CPM test and greater pain catastrophizing at 1 month after injury.

The National Institute for Health and Care Excellence provides evidence-based advice that guides clinical practice. We highlight major criticisms related to the new guideline for chronic primary pain., Summary The National Institute for Health and Care Excellence should revise their recent guideline to take into account all the available evidence on the treatment of chronic primary pain.

A protocol for a systematic review examining how central sensitisation questionnaires correlate with sensory or psychological measures to clarify the use of “central sensitisation” in clinical contexts., Introduction: Central sensitization (CS) was first defined in animal studies to be increased nociceptive responsiveness due to sensitization of neurons in the central nervous system, usually the result of prolonged nociceptive input or a disease state. Recently, the concept of CS has been adopted in clinical assessments of chronic pain, but its diagnosis in humans has expanded to include the enhancement of a wide range of nociceptive, sensory, and emotional responses. Many poorly understood pain disorders are referred to as “central sensitivity syndrome,” a term associated with a broad range of hypervigilant sensory and emotional responses. Diagnosis often involves a review of medical records and an assessment of behaviour, emotional disposition, and overall sensitivity of a patient. Obviously, these assessments are unable to directly capture the responsiveness of nociceptive neurons. The purpose of this review is to ascertain whether self-report questionnaires associated with central sensitization and the diagnosis of central sensitivity syndrome are associated with enhanced nociceptive responses or whether they more validly measure sensitivity in a broader sense (ie, including emotional responses). Methods: Following the PRISMA guidelines, a detailed search of studies that involve the Central Sensitization Inventory or Pain Sensitivity Questionnaire correlated with either nociceptive sensory tests (quantitative sensory testing) or emotional hypervigilance (anxiety, depression, stress, etc) will be conducted on MEDLINE, PsychINFO, and Web of Science. Perspective: The review is expected to synthesize correlations between sensitivity questionnaires and nociceptive or emotional sensitivity to determine whether these questionnaires reflect a broadened understanding of the term “central sensitization.”

Understanding the complex, multifactorial nature of chronic pelvic pain can help physicians determine the pain's etiology and thus refer specialists to include in the multidisciplinary treatment required., Chronic pelvic pain (CPP) is a highly prevalent condition which is underdiagnosed and poorly understood. The purpose of this review is to outline the various aspects of the nature of CPP, including its etiologies, clinical presentation, and nonoperative treatment options. For data collection, a PubMed search was conducted using indexing terms such as chronic pelvic pain and pelvic pain. Literature reviews and studies focusing on etiologies, clinical presentation, and/or the diagnosis of CPP were compiled for review by a team of 3 physiatrists. Studies investigating conservative treatments, medications, and interventional procedures for CPP and related conditions with comparable etiologies were also included. Of the 502 articles retrieved, 116 were deemed suitable by the team for this study. Although CPP is a complex, multifaceted condition, a particular susceptibility to nociceptive stimuli was demonstrated as an underlying theme in its evolution. There are many treatment options currently used; however, more robust evidence, such as randomized controlled trials, are needed before creating comprehensive guidelines for treating CPP.

Supplemental Digital Content is Available in the Text. A third of patients improved simultaneously in several domains, and a third improved in few or none. Pain intensity was the least likely outcome to improve., Introduction: Chronic pain is treated with multimodal rehabilitation programs, targeting improvement in several health aspects. These treatments must be evaluated multidimensionally, which is a methodological challenge. Objectives: This study investigated factors (demographic, pain-related, and individual- vs group-based treatment) predicting successful outcomes after multimodal pain rehabilitation programs. Methods: Data from 3 outpatient clinics were retrieved from the Swedish Quality Registry for Pain Rehabilitation, for 314 patients (218 women). Outcome variables were dichotomized as binary change (improved or not improved) based on clinical thresholds. Total improvement grouped outcomes into 0 to 2, 3 to 4, and 5 to 6 improved variables. Binary logistic regression analyses investigated the association between the baseline predictors and change variables. Results: Patients improving after treatment ranged from 34% (pain intensity) to 80% (depression) for women and 34% to 76% for men, respectively. Total improvement outcome was consistent (after treatment and 1 year) with 28% of patients improving on 5 to 6 outcomes. The baseline predictor related to most improved outcomes was pain intensity, with positive correlation to improvement in pain intensity (P < 0.001) and negative correlation with improvements in anxiety (P = 0.075) and depression (P = 0.002). Individual-based treatment, compared with group-based treatment, was associated with improvement in pain intensity (P = 0.008). Conclusions: About a third of patients improved in several outcomes by the end of a multimodal program, with most improvement for depression and least for pain intensity. Generally, patients with more severe health status at baseline improve most directly after treatment, but these findings could not suggest treatment adjustments that would improve overall success rates.

Ketamine-induced dissociation and analgesia are independent and robust to general anesthesia neural circuit alterations, suggesting that ketamine can be refined into a targeted pain therapeutic., Introduction: Ketamine, an anesthetic adjunct, is routinely administered as part of a balanced general anesthetic technique. We recently showed that the acute analgesic and dissociation properties of ketamine are separable to suggest that distinct neural circuits underlie these states. Objective: We aimed to study whether this finding is robust to the substantial neural circuit alterations associated with general anesthesia. Methods: We conducted a single-site, open-label, randomized controlled, cross-over study of sevoflurane and sevoflurane-plus-ketamine (SK) general anesthesia in healthy subjects (n = 12). Before and after general anesthesia, we assessed precalibrated cuff pain intensity and nociceptive pain quality as well as dissociation using the Clinician-Administered Dissociative States Scale (CADSS). For statistical inference, we ran a variation of backward elimination repeated-measures analysis of covariance. Models with CADSS as a covariate term were used to assess whether dissociation mediated the effect of ketamine on pain intensity and quality. Results: Sevoflurane-plus-ketamine general anesthesia was associated with a significant (P = 0.0002) pain intensity decline of 3 (SE, 0.44). There was an order effect for dissociation such that SK was associated with a significant (P = 0.0043) CADSS increase of 17.8 (3.2) when the SK treatment came first. When the pain intensity model was reanalyzed with CADSS as an additional covariate, the effect of CADSS was not significant. These results were also conserved for pain quality. Conclusions: Our findings suggest that the analgesic and dissociation properties of ketamine remain separable despite general anesthesia. Thus, ketamine may be used as a probe to advance our knowledge of dissociation independent pain circuits.

Both pain rating and exponential model revealed that percutaneous endoscopic lumbar discectomy provided rapid pain recovery that was maintained for at least 3 months compared with conservative treatments., Introduction: Lumbar disc herniation (LDH) is a common back disorder that evokes back and/or leg pain. Percutaneous endoscopic lumbar discectomy (PELD) is a minimally invasive surgery for patients with LDH. However, there is little evidence of effectiveness of PELD compared with conservative treatments. Objective: The goal of this study was to quantify the efficacy of PELD compared with conservative treatments. Methods: Here, we conducted a prospective observational cohort study using momentary pain assessments via a smartphone app during 3 months following surgery. The trajectories of daily ecological momentary pain assessments were fitted with an exponential model containing two parameters: a pain reduction coefficient and the percentage of persistent pain. To control for selection bias between PELD and Conservative groups (N = 167 and 34), we used inverse probability (IP) of treatment weighting for statistical comparisons. Results: Compared with conservative treatments, both momentary pain rating and the exponential model showed statistically significant pain recovery following PELD (p < 0.001). In addition, PELD had a faster pain recovery rate (hazard ratio (95% confidence interval): 1.75 (1.40, 2.20), p < 0.001), greater overall pain recovery rate (odds ratio (95%CI): 2.35 (2.01, 5.26), p < 0.001), faster pain reduction (t199 = 3.32, p = 0.001), and lower estimated persistent pain (Z = 2.53, p = 0.011). Greater pain intensity and lower anxiety before the surgery were predictors of faster pain reduction in the recovery subgroup following PELD. Conclusions: In conclusion, momentary pain rating and the model fitting revealed that PELD provided rapid pain recovery that lasted for at least three months. Greater pain intensity and lower anxiety before the surgery were predictors of faster pain reduction in the recovery subgroup following PELD. Daily momentary pain rating on a smartphone may be able to provide more informative data to evaluate effect of an intervention than pain assessment on hospital visits.

Supplemental Digital Content is Available in the Text. Evidence-informed guidance to better leverage, implement, and select virtual care platforms for pediatric chronic pain, and identified knowledge gaps are in need of additional research., The COVID-19 pandemic has acutely challenged health systems and catalyzed the need for widescale virtual care and digital solutions across all areas of health, including pediatric chronic pain. The objective of this rapid systematic review was to identify recommendations, guidelines, and/or best practices for using virtual care to support youth with chronic pain and their families (CRD42020184498). MEDLINE, CINAHL, Embase, APA PsychINFO, and Web of Science were searched the week of May 25, 2020, for English language peer-reviewed articles published since 2010 that (1) discussed children and adolescents aged 3 months); (2) focused on any type of virtual care (eg, telephone, telehealth, telemedicine, mHealth, eHealth, online, or digital); and (3) reported on guidelines, best practices, considerations, or recommendations for virtual care. Abstract and full text screening and data extraction were performed in duplicate. Meta-ethnography was used to synthesize concepts across articles. Of 4161 unique records screened, 16 were included addressing diverse virtual care and pediatric chronic pain conditions. Four key themes were identified: (1) opportunities to better leverage virtual care, (2) direct effective implementation of virtual care, (3) selection of virtual care platforms, and (4) gaps in need of further consideration when using virtual care to support youth with chronic pain and their families. No existing guidelines for virtual care for pediatric chronic pain were identified; however, best practices for virtual care were identified and should be used by health professionals, decision makers, and policymakers in implementing virtual care.

Supplemental Digital Content is Available in the Text. We report an increased slow-to-fast alpha power ratio of neurophysiological activity in chronic pain from known pain-processing areas, among others., Introduction: Objective disease markers are a key for diagnosis and personalized interventions. In chronic pain, such markers are still not available, and therapy relies on individual patients' reports. However, several pain studies have reported group-based differences in functional magnetic resonance imaging, electroencephalography, and magnetoencephalography (MEG). Objectives: We aimed to explore spectral differences in resting-state MEG brain signals between patients with chronic pain and pain-free controls and to characterize the cortical and subcortical regions involved. Methods: We estimated power spectral density over 5 minutes of resting-state MEG recordings in patients with chronic pain and controls and derived 7 spectral features at the sensor and source levels: alpha peak frequency, alpha power ratio (power 7–9 Hz divided by power 9–11 Hz), and average power in theta, alpha, beta, low-gamma, and high-gamma bands. We performed nonparametric permutation t tests (false discovery rate corrected) to assess between-group differences in these 7 spectral features. Results: Twenty-one patients with chronic pain and 25 controls were included. No significant group differences were found in alpha peak frequency or average power in any frequency band. The alpha power ratio was significantly higher (P < 0.05) in patients with chronic pain at both the sensor and brain source levels. The brain regions showing significantly higher ratios included the occipital, parietal, temporal and frontal lobe areas, insular and cingulate cortex, and right thalamus. Conclusion: The alpha power ratio is a simple, promising signal marker of chronic pain, affecting an expansive range of cortical and subcortical regions, including known pain-processing areas.

Supplemental Digital Content is Available in the Text. The CARE Scale-7 is the first validated instrument to assess self-care difficulty in both sexes and may promote individualized care planning among chronic pain patients., Objectives: Social and interpersonal factors impact the trajectory of chronic pain. We previously developed and validated a 2-factor, 7-item measure to assess interpersonal factors, including relationship guilt and worry and difficulty prioritizing self-care in chronic pain. Here, we confirm the factor structure and examine the sex invariance of the two-factor structure of the CARE Scale-7. Methods: Data were collected as part of routine clinical care at a tertiary pain clinic using the Collaborative Health Outcomes Information Registry. Patient participants (67% women) were predominantly middle-aged (M = 50.9 years, SD = 17.8), married (55.2%), and White/non-Hispanic (55.7%). Data included demographics, pain characteristics, CARE Scale-7, pain catastrophizing, and Patient-Reported Outcomes Measurement Information System psychological and physical function measures. Confirmatory factor analysis was conducted to validate the factor structure of the CARE Scale, and a stepwise approach to measurement invariances by sex examined configural, metric, and scalar invariance. Results: Internal consistency of the scale items ensured suitability for factor analyses. Confirmatory factor analysis findings revealed an overall good fit of the 2-factor model among males and females and that CARE Scale-7 is in fact sex invariant. Finally, CARE Scale-7 showed convergent validity with pain-related outcomes. Discussion: The CARE Scale is the first validated instrument to assess self-care in both sexes among patients with chronic pain. The subscale of difficulty prioritizing self-care emerged as a potentially unique factor that should be integrated in clinical assessment. CARE Scale may facilitate standardized measurement in research and clinical contexts, which may inform a comprehensive treatment focus that integrates individualized self-care planning.

Supplemental Digital Content is Available in the Text. Most patients with childhood-onset complex regional pain syndrome continue to have some complex regional pain syndrome–related pain into young adulthood and have a lower health-related quality of life., Introduction: Complex regional pain syndrome (CRPS) is a neuropathic pain condition of unknown etiology. Little is known of long-term outcomes of young adults who were diagnosed with CRPS as children. Methods: In this study, surveys were mailed to adults who were treated for childhood CRPS at the Lucile Packard Children's Hospital between 1994 and 2018. Completed surveys were analyzed for pain symptoms. Health-related quality-of-life surveys, the Optum SF-8, were analyzed based on norm-based scoring. Results: This study had a 50% response rate. Patients were treated with physical and occupational therapy, peripheral or sympathetic nerve blocks, medication for neuropathic pain, and psychotherapy. Sixty-eight percent of the subjects reported pain. Each 1-year increase in the patient's age at the time of CRPS diagnosis increased the odds of having at least mild pain as an adult by 61% (P = 0.005). Most patients had slightly lower quality-of-life scores than the US population average in both the mental component score (43.4, 95%, confidence interval 3.4) and the physical component score (44.4, 95%, confidence interval 3.3). Conclusions: Young adults in our sample had long-lasting pain symptoms. More than two-thirds of adult patients reported some degree of pain, and these patients had a lower quality of life. Encouraging was that the majority did not have CRPS spreading to other areas, and their pain did not warrant further treatment. Understanding long-term outcomes may lead to risk stratification earlier in the disease to improve future quality of life.

Supplemental Digital Content is Available in the Text. None of the mindfulness-based clinical trials for chronic pain included in this review analyzed the interaction effects between mindfulness interventions and concomitant analgesic drug therapies., Most patients with chronic pain do not find adequate pain relief with a single treatment, and accumulating evidence points to the added benefits of rational combinations of different treatments. Given that psychological therapies, such as mindfulness-based interventions (MBIs), are often delivered in conjunction with concomitant analgesic drug therapies (CADTs), this systematic scoping review examines the evidence for any interactions between MBIs and CADTs. The protocol for this review has been published and registered. MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and PsycINFO databases were searched until July 2019. We included randomized controlled trials that evaluated the efficacy of MBIs for the treatment of chronic pain. A total of 40 randomized controlled trials (2978 participants) were included. Thirty-nine of 40 (97.5%) included mindfulness-based clinical trials allowed the use of CADTs. However, only 6 of these 39 (15.4%) trials provided adequate details of what these CADTs were, and only 4 (10.3%) trials controlled for CADTs. Of great relevance to this review, none of the included trials analyzed the interactions between MBIs and the CADTs to determine whether they have an additive, synergistic, or antagonistic effect on chronic pain. Adverse events were inconsistently reported, and no judgment could be made about safety. Future trials assessing the interactions between MBIs and CADTs, with better harms reporting, are needed to better define the role of MBIs in the management of chronic pain.

Supplemental Digital Content is Available in the Text. Latinx-Americans showed greater temporal summation, adversity, and adversity correlates relative to non-Hispanic Whites. Discrimination and lifespan social status change inversely related to summation for Latinx-Americans., Introduction: Adverse life experiences disproportionately impact Latinx-Americans and are related to greater chronic pain rates. However, little is known about how adversities interact with central pain mechanisms for the development of later pain among Latinx-Americans. Objectives: The current study examined the relationship between adverse life experiences (eg, trauma and ethnic discrimination) and correlates (eg, social status) with mechanical temporal summation of pain (a proxy measure of central sensitization) between pain-free U.S. native Latinx (n = 65) and non-Hispanic White (NHW) (n = 51) adults. Methods: Participants completed self-report adverse life experience and correlational measures regarding childhood and adulthood and a mechanical temporal summation protocol. Results: Relative to NHWs, Latinx-Americans reported experiencing significantly greater trauma, discrimination, and lower social status during childhood and adulthood, along with greater temporal summation. Contrary to hypotheses, recent and lifetime experiences of ethnic discrimination significantly correlated with less temporal summation among Latinx-Americans. Decreases in objective and subjective social status across the lifespan (childhood to present day) correlated with greater temporal summation for Latinx-Americans. However, r-to-z transformation analyses confirmed that significant adversity and social status correlations observed among the Latinx group did not significantly differ from NHW participants. Conclusions: The present findings highlight the complex association between adverse experiences, adverse experience risk factors, and pain for Latinx-Americans. Given the disproportion of experienced pain and adversity among Latinx-Americans, the current findings suggest that a better understanding of the unique adversities for this sample may help elucidate the mechanisms underlying the relationship between adversities, adversity correlates, and pain risk for Latinx-Americans.

Supplemental Digital Content is Available in the Text., Introduction: Critical for the diagnosis and treatment of chronic pain is the anatomical distribution of pain. Several body maps allow patients to indicate pain areas on paper; however, each has its limitations. Objectives: To provide a comprehensive body map that can be universally applied across pain conditions, we developed the electronic Collaborative Health Outcomes Information Registry (CHOIR) self-report body map by performing an environmental scan and assessing existing body maps. Methods: After initial validation using a Delphi technique, we compared (1) pain location questionnaire responses of 530 participants with chronic pain with (2) their pain endorsements on the CHOIR body map (CBM) graphic. A subset of participants (n = 278) repeated the survey 1 week later to assess test–retest reliability. Finally, we interviewed a patient cohort from a tertiary pain management clinic (n = 28) to identify reasons for endorsement discordances. Results: The intraclass correlation coefficient between the total number of body areas endorsed on the survey and those from the body map was 0.86 and improved to 0.93 at follow-up. The intraclass correlation coefficient of the 2 body map graphics separated by 1 week was 0.93. Further examination demonstrated high consistency between the questionnaire and CBM graphic (

Supplemental Digital Content is Available in the Text. Clinical utility and interrater agreement of the ICD-11 chronic pain classification will be assessed in countries of different income categories investigating its global applicability., Introduction: The purpose of the present ecological implementation field study is to evaluate the new classification of chronic pain as implemented in the 11th revision of the International Classification of Diseases (ICD-11) with regard to clinical utility and interrater reliability. To evaluate the classification in a variety of settings, the study will be implemented in different low-, middle-, and high-income countries. Methods: The study will be conducted in 2 phases. Participating pain clinics of the first phase are located in India, Cuba, and New Zealand. Two or more clinicians per study center will use the ICD-11 classification of chronic pain to diagnose 75 to 100 consecutive new chronic pain patients per center. A structured classification algorithm will guide the diagnostic process. Interrater reliability will be analyzed for the first 20 consecutive new patients per center. Before the coding, a training workshop will introduce the clinicians to the new classification. The main outcome parameter of the ecological implementation field study is clinical utility. More specifically, this entails clinical utility ratings, interrater reliability, as well as the exhaustiveness of the classification and the mutual exclusiveness of the new chronic pain categories. Differences between countries with different cultural backgrounds and income levels will be analyzed. Perspective: The ecological implementation field study presented here will be implemented in several countries with different income levels. This increases the generalizability of the results and allows initial insight into the global applicability of the new chronic pain classification. A positive evaluation can facilitate the implementation of the classification.

Study findings reveal continued opioid reduction and enduring pain stability for a substantial fraction of patients, 2 to 3 years after a patient-centered voluntary opioid tapering program., Objective: We previously reported promising results for a 4-month patient-centered voluntary opioid tapering study. Key questions remain about the durability of effects and possible risks after opioid reduction. We provide the longest follow-up data to date for prospective opioid tapering: 2- to 3-year follow-up for pain intensity and daily opioid use in a subset of patients from our original 4-month opioid tapering study. Methods: Twenty-three patients (44% of original sample) responded to contact attempts through telephone and reported their average pain intensity and current opioid use. Opioid doses were converted to morphine equivalent daily dose (MEDD). Data were analyzed within a repeated-measures model where time (baseline, 4 months, and 2–3 years) was the within-subject factor. Results: Among reachable patients, the effect of time on change in MEDD from baseline to 4 months to 2 to 3 years was significant. Since baseline, 20 (95%) of the current sample reduced MEDD, and 15 (71%) further reduced MEDD at 2- to 3-year follow-up. There was no effect of time on change in pain intensity from baseline to 4 months to 2 to 3 years. Since baseline, 11 (52%) of the current sample reported pain reduction, and 12 (57%) reported reduced pain from the 4-month follow-up to the 2- to 3-year follow-up. Five (24%) reported increased pain intensity. Conclusion: Study findings reveal continued MEDD reduction and enduring pain stability 2 to 3 years after a patient-centered voluntary opioid tapering program for a substantial fraction of patients. Notably, we were not able to verify current opioid use through medical records and were limited by self-report.

Introduction:. Offset analgesia (OA) and conditioned pain modulation (CPM) are frequently used paradigms to assess the descending pain modulation system. Recently, it was shown that both paradigms are reduced in chronic pain, but the influence of acute pain has not yet been adequately examined. Objectives:. The aim of this study is to investigate OA and CPM after exercise-induced pain to evaluate whether these tests can be influenced by delayed-onset muscle soreness (DOMS) at a local or remote body site. Methods:. Forty-two healthy adults were invited to 3 separate examination days: a baseline appointment, the consecutive day, and 7 days later. Participants were randomly divided into a rest (n = 21) and an exercise group (n = 21). The latter performed a single intensive exercise for the lower back. Before, immediately after, and on the following examination days, OA and CPM were measured at the forearm and the lower back by blinded assessor. Results:. The exercise provoked a moderate pain perception and a mild delayed-onset muscle soreness on the following day. Repeated-measurements analysis of variance showed no statistically significant main effect for either OA or CPM at the forearm or lower back (P > 0.05). Conclusion:. Delayed-onset muscle soreness was shown to have no effect on the inhibitory pain modulation system neither locally (at the painful body part), nor remotely. Thus, OA and CPM are robust test paradigms that probably require more intense, different, or prolonged pain to be modulated.

Supplemental Digital Content is Available in the Text., Pain-related memory biases have been frequently explored in individuals with chronic pain, and along with attentional and interpretation biases are hypothesised to contribute to the onset and/or maintenance of chronic pain. The aim of this review is to provide a systematic review and synthesis of studies exploring memory recall biases for pain-related information in individuals with chronic pain relative to healthy controls and the recall of neutral information. Studies were identified through a search of Medline, PsychINFO, Web of Science, CINAHL, Cochrane Library, and Open Grey databases. Search terms were memory, recall, recognition, and bias*, intersected with pain. Eighteen studies meeting the inclusion criteria were included. Subset meta-analyses are also reported from 12 studies with relevant between-groups data (comparing recall in chronic pain vs healthy control groups) and 12 studies with relevant within-groups data (eg, comparing recall of pain-related/emotional vs neutral words). Between-groups analysis revealed significantly weaker recall bias for affective-pain words in individuals with chronic pain relative to healthy controls, but only when nondepressed chronic pain individuals were included. No significant differences were found between groups in the recall of sensory-pain, illness-related, or depression-related words. Within-groups analysis revealed individuals with chronic pain show a significant recall bias favouring sensory-pain words relative to neutral and affective-pain words, and a bias for illness-related words relative to depression-related words. A recall bias favouring neutral words was found in healthy individuals. Evidence for the presence of pain-related memory biases in patients with chronic pain is inconclusive. Further methodologically rigorous research is required.

We present a case series of patients treated with hydroxychloroquine for complex regional pain syndrome and demonstrated analgesia and reduced spinal cord autoinflammation in a preclinical model of complex regional pain syndrome., Introduction: Complex regional pain syndrome (CRPS) is a condition that occurs after minor trauma characterized by sensory, trophic, and motor changes. Although preclinical studies have demonstrated that CRPS may be driven in part by autoinflammation, clinical use of immune-modulating drugs in CRPS is limited. Hydroxychloroquine (HCQ) is a disease-modifying antirheumatic drug used to treat malaria and autoimmune disorders that may provide benefit in CRPS. Objectives: To describe the use of HCQ in patients with refractory CRPS and investigate possible mechanisms of benefit in a mouse model of CRPS. Methods: We initiated HCQ therapy in 7 female patients with refractory CRPS undergoing treatment at the Stanford Pain Management Center. We subsequently undertook studies in the mouse tibial fracture–casting model of CRPS to identify mechanisms underlying symptom reduction. We evaluated behavior using mechanical allodynia and spinal cord autoinflammation by immunohistochemistry and enzyme-linked immunosorbent assay. Results: We treated 7 female patients with chronic, refractory CRPS with HCQ 200 mg twice daily for 2 months, followed by 200 mg daily thereafter. Two patients stopped HCQ secondary to lack of response or side effects. Overall, HCQ significantly improved average numerical rating scale pain from 6.8 ± 1.1 before HCQ to 3.8 ± 1.9 after HCQ treatment. In the tibial fracture–casting mouse model of CRPS, we observed reductions in allodynia, paw edema, and warmth following daily HCQ treatment starting at 3 weeks after injury. Spinal cord dorsal horn microglial activation and cytokine levels were also reduced by HCQ treatment. Conclusion: Together, these preclinical and clinical results suggest that HCQ may benefit patients with CRPS at least in part by modulating autoinflammation and support further investigation into the use of HCQ for CRPS.

Introduction:. Most current chronic pain treatment strategies have limitations in effectiveness and tolerability, and accumulating evidence points to the added benefits of rational combinations of different therapies. However, most published clinical trials of treatment combinations have involved combinations of 2 drugs, whereas very little research has been performed to characterize interactions between drug and nondrug interventions. Mindfulness-based interventions (MBIs) have been emerging as a safe and potentially effective treatment option in the management of chronic pain, but it is unclear how MBIs can and should be integrated with various other pain treatment interventions. Thus, we seek to review available clinical trials of MBIs for chronic pain to evaluate available evidence on the interactions between MBIs and various pharmacological treatments. Methods:. A detailed search of trials of MBIs for the treatment of chronic pain in adults will be conducted on the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO from their inception until the date the searches are run to identify relevant randomized controlled trials. Primary outcomes will include the following: (1) what concomitant analgesic drug therapies (CADTs) were allowed; (2) if and how trials controlled for CADTs and analyzed their interaction; and (3) results of available analyses of interactions between the MBI and CADT. Perspective:. This review is expected to synthesize available evidence describing the interactions between MBIs and various studied drug therapies for chronic pain. Available evidence may help inform the rational integration of MBIs with drug therapy for chronic pain.

Supplemental Digital Content is Available in the Text. This study reveals sex-specific DNA methylation signatures in human T cells that discriminate chronic low back pain participants from healthy controls., Objective: Determine if chronic low back pain (LBP) is associated with DNA methylation signatures in human T cells that will reveal novel mechanisms and potential therapeutic targets and explore the feasibility of epigenetic diagnostic markers for pain-related pathophysiology. Methods: Genome-wide DNA methylation analysis of 850,000 CpG sites in women and men with chronic LBP and pain-free controls was performed. T cells were isolated (discovery cohort, n = 32) and used to identify differentially methylated CpG sites, and gene ontologies and molecular pathways were identified. A polygenic DNA methylation score for LBP was generated in both women and men. Validation was performed in an independent cohort (validation cohort, n = 63) of chronic LBP and healthy controls. Results: Analysis with the discovery cohort revealed a total of 2,496 and 419 differentially methylated CpGs in women and men, respectively. In women, most of these sites were hypomethylated and enriched in genes with functions in the extracellular matrix, in the immune system (ie, cytokines), or in epigenetic processes. In men, a unique chronic LBP DNA methylation signature was identified characterized by significant enrichment for genes from the major histocompatibility complex. Sex-specific polygenic DNA methylation scores were generated to estimate the pain status of each individual and confirmed in the validation cohort using pyrosequencing. Conclusion: This study reveals sex-specific DNA methylation signatures in human T cells that discriminates chronic LBP participants from healthy controls.

Supplemental Digital Content is Available in the Text. A pilot study assessing whether psychophysiologic symptom relief therapy can reduce nonspecific back pain compared with usual care and mindfulness-based stress reduction., Introduction: Chronic back pain is the leading cause of disability in the United States. Based on the hypothesis that nonspecific back pain may be rooted in a psychophysiologic etiology, we propose a new approach to chronic back pain. Objectives: A pilot study was conducted to assess whether psychophysiologic symptom relief therapy (PSRT) can reduce disability and back pain bothersomeness for patients with chronic back pain. Methods: This was a three-armed, randomized trial for adults with nonspecific chronic back pain that compared PSRT with usual care and an active comparator (mindfulness-based stress reduction [MBSR]). Psychophysiologic symptom relief therapy–randomized participants received a 12-week (36 hours) course based on the psychophysiological model of pain. All groups were administered validated questionnaires at baseline and at 4, 8, 13, and 26 weeks. The primary outcome was the reduction in pain disability measured by the Roland–Morris Disability Questionnaire. Results: The mean Roland–Morris Disability Questionnaire score for the PSRT group (n = 11) decreased from 9.5 (±4.3 SDs) to 3.3 (±5.1) after 26 weeks which was statistically significant compared with both MBSR (n = 12) (P = 0.04) and usual care (n = 12) (P = 0.03). Pain bothersomeness scores and pain-related anxiety decreased significantly over 26 weeks in PSRT compared with MBSR and usual care (data in manuscript). At 26 weeks, 63.6% of the PSRT arm reported being pain free (0/10 pain) compared with 25.0% and 16.7% in MBSR and usual care arms, respectively. Psychophysiologic symptom relief therapy attendance was 76%, and there was 100% follow-up of all groups. Conclusion: Psychophysiologic symptom relief therapy is a feasible and potentially highly beneficial treatment for patients with nonspecific back pain.

How obesity affects pain sensitivity in pain-free individuals remains to be fully characterized. Quantitative sensory testing revealed that obese individuals had responses to heat and cold pain that were indistinguishable from nonobese individuals. Thus, obesity alone does not appear to be associated with amplification of nociceptive processing., Introduction: There is emerging evidence suggesting a relationship between obesity and chronic pain. Objectives: The aim of this study was to determine whether pain-free obese individuals display altered pain responses to acute noxious stimuli, thus raising the possibility of greater pain sensitivity and potential susceptibility for chronic pain development. Methods: Psychophysical and anthropometric data were collected from 38 individuals with an obese body mass index (BMI) classification (BMI ≥ 30) and 41 age/sex-matched individuals of a healthy BMI (BMI < 24.9). Because BMI may be an inaccurate index of obesity, additional anthropometric parameters of central adiposity and percent body fat were examined. Pain responses to suprathreshold noxious heat and cold stimuli were examined. Subjects provided pain intensity and unpleasantness ratings to noxious heat (49°C) applied at varying durations and locations (ventral forearm/lower leg). Cold pain ratings, thresholds, and tolerances were obtained after immersion of the hand in a cold-water bath (0–2°C). Between-group differences in pain responses, as well as relationships between pain responses and obesity parameters, were examined. Importantly, confounds that may influence pain such as anxiety, depression, impulsivity, sleepiness, and quality of life were assessed. Results: No between-group differences in pain sensitivity to noxious heat and cold stimuli were found. No relationships were found between central adiposity or body fat (percentage or distribution) and pain responses to noxious heat or cold stimuli. Conclusions: Obesity has minimal influence on pain sensitivity. Accordingly, it is unlikely that obesity alone increases susceptibility for chronic pain development through amplification of nociceptive processes.

Supplemental Digital Content is Available in the Text. Dry needling has analgesic effects in shoulder pain associated with myofascial pain syndrome. The analgesic effects last for up to 1 week., Introduction: Myofascial pain syndrome (MPS) affects most patients with chronic shoulder pain. Dry needling (DN) is a common treatment for MPS, but its temporal pattern and sensory effects remain unknown. Objectives: We evaluated in a randomized, sham-controlled study the pattern of analgesic efficacy and local sensory changes of a single session of DN for MPS in patients with chronic shoulder pain. Methods: Patients with chronic shoulder pain were randomized into active (n = 20) or sham (n = 21) groups. A single DN was performed by a researcher blinded to group assignment and pain outcomes. Pain intensity was assessed by the numeric rating score, and sensory thresholds were evaluated with a quantitative sensory testing protocol, including the area of tactile sensory abnormalities 7 days before needling, right before, and 7 days after the intervention. Results: Dry needling led to significant larger pain intensity reduction (from 6.30 ± 2.05 to 2.40 ± 2.45 in the active group; P = 0.02, effect size = −1.3 (95% CI [−2.0 to −0.68]); (number necessary to treat = 2.1). Pain reduction scores were significantly different on the second day after needling and persisted so until the seventh day and were accompanied by improvement in other dimensions of pain and a decrease in the area of mechanical hyperalgesia in the active DN group alone (P < 0.05). Conclusion: Active trigger points DN provided analgesic effects compared with sham and decreased the area of local mechanical hyperalgesia. These findings have practical clinical implications and may provide mechanistic insights behind MPS.

Supplemental Digital Content is Available in the Text. There is evidence that joint and nerve mobilisations compared with sham or no intervention positively influence various neuroimmune responses in animal and human neuromusculoskeletal conditions., Several animal and human studies revealed that joint and nerve mobilisations positively influence neuroimmune responses in neuromusculoskeletal conditions. However, no systematic review and meta-analysis has been performed. Therefore, this study aimed to synthesize the effects of joint and nerve mobilisation compared with sham or no intervention on neuroimmune responses in animals and humans with neuromusculoskeletal conditions. Four electronic databases were searched for controlled trials. Two reviewers independently selected studies, extracted data, assessed the risk of bias, and graded the certainty of the evidence. Where possible, meta-analyses using random effects models were used to pool the results. Preliminary evidence from 13 animal studies report neuroimmune responses after joint and nerve mobilisations. In neuropathic pain models, meta-analysis revealed decreased spinal cord levels of glial fibrillary acidic protein, dorsal root ganglion levels of interleukin-1β, number of dorsal root ganglion nonneuronal cells, and increased spinal cord interleukin-10 levels. The 5 included human studies showed mixed effects of spinal manipulation on salivary/serum cortisol levels in people with spinal pain, and no significant effects on serum β-endorphin or interleukin-1β levels in people with spinal pain. There is evidence that joint and nerve mobilisations positively influence various neuroimmune responses. However, as most findings are based on single studies, the certainty of the evidence is low to very low. Further studies are needed.

Screening tools allowing to predict poor pain outcomes are widely used. Often these screening tools contain psychosocial risk factors. This review (1) identifies multidimensional screening tools that include psychosocial risk factors for the development or maintenance of pain, pain-related distress, and pain-related disability across pain problems in adults, (2) evaluates the quality of the validation studies using Prediction model Risk Of Bias ASsessment Tool (PROBAST), and (3) synthesizes methodological concerns. We identified 32 articles, across 42 study samples, validating 7 screening tools. All tools were developed in the context of musculoskeletal pain, most often back pain, and aimed to predict the maintenance of pain or pain-related disability, not pain-related distress. Although more recent studies design, conduct, analyze, and report according to best practices in prognosis research, risk of bias was most often moderate. Common methodological concerns were identified, related to participant selection (eg, mixed populations), predictors (eg, predictors were administered differently to predictors in the development study), outcomes (eg, overlap between predictors and outcomes), sample size and participant flow (eg, unknown or inappropriate handling of missing data), and analysis (eg, wide variety of performance measures). Recommendations for future research are provided. ispartof: PAIN Reports vol:4 issue:5 pages:e775-e775 ispartof: location:United States status: Published online

Supplemental Digital Content is Available in the Text. In this protocol for a cohort study, an approach to characterize new-onset or worsening neuropathic pain in patients with COVID-19 is described., Introduction and Objectives: The coronavirus disease 2019 (COVID-19) pandemic has resulted in patients experiencing symptoms that include neurological dysfunction. As many viral infections are associated with neuropathy, the aim of the study is to characterize the incidence and severity of neuropathic pain in patients with COVID-19. Methods: A cohort study will be conducted in adult (≥18 years) patients who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at Washington University/Barnes-Jewish Hospital. Participants who are deceased, with incomplete test results, or who cannot be contacted will be excluded. Approximately 1320 participants will be recruited in a 1:2 ratio of those with a positive-to-negative SARS-CoV-2 test result. Each participant will be invited to complete a survey to assess their symptoms related to neuropathy, 30 to 90 days after their initial SARS-CoV-2 test. Survey responses, demographics, and clinical data from the electronic health record will be used for analysis. The primary outcome is the incidence of new symptoms of neuropathic pain. The self-reported DN4 and Neuropathic Pain Symptom Inventory questionnaires (Appendix 1, http://links.lww.com/PR9/A103) will be used for neuropathic pain screening and severity assessment, respectively. Exploratory analyses will be performed to investigate other potential clinical endpoints and trends. Results/Conclusion: Similar to previous coronavirus infections, an increased incidence of new-onset neuropathic pain after COVID-19 disease is expected, along with an increase in the severity experienced by patients with COVID-19 with pre-existing chronic pain. Comprehensive understanding of how COVID-19 affects the nervous system can provide a better framework for managing pain in this disease.

Supplemental Digital Content is Available in the Text. The unique chronic pain experience in emerging adults (18–29 years) has not been widely studied. Here, we provide an integrated summary of the available evidence., Much of the adult chronic pain literature addresses pain in typical pain cohorts of middle-aged to older individuals. To date, little research has focused on chronic pain in younger adults, who likely have a completely different pain experience. This scoping review aimed to address this gap by describing the emerging adult (18–29 years) chronic pain experience regarding prevalence, associated factors, outcomes, and pain management. Searches of primary electronic databases including PubMed, Embase, PsycINFO, and CINAHL were performed on February 26, 2020, restricting the publication date from database inception to December 31, 2019. The search strategy, conducted in English, covered search term combinations of “chronic pain” and “young adults.” A total of 6,612 records were considered—3,141 after removing duplicates. These records were screened by title and abstract; 871 through full-text screening. Of these, 78 articles covered the topic of emerging adults with chronic pain. Collectively, results indicated that between 5% and 30% of emerging adults experience chronic pain, depending on the sample and exact chronic pain definition. The most consistent associated factors were female sex, familial chronic pain, and previous experiences of chronic pain in childhood. Anxiety, depression, and sleep issues appeared associated both before and after the onset of chronic pain. Outcomes of pain included interruptions to study and work, poorer physical functioning, and pain-related interference to socializing. We observed that few pain treatments have been tested specifically in this cohort. A greater ongoing focus on chronic pain in emerging adults is required to improve long-lasting outcomes.

Sensory abnormalities through quantitative sensory testing in fibromyalgia were not substantially influenced by psychological comorbidities. A significant subgroup showed signs of central sensitization, influenced by pain intensity., Introduction: Patients suffering from fibromyalgia syndrome (FMS) are heterogenous. They often present with sensory abnormalities and comorbidities. Objectives: We aimed to answer the following questions: (1) Is there a specific somatosensory profile in our patient cohort? (2) Can we detect subgroups characterized by a specific combination of sensory and psychological features? and (3) Do psychological parameters influence sensory signs? Methods: In 87 patients with FMS quantitative sensory testing was performed on the hand and evaluated in combination with questionnaire results regarding pain, psychological comorbidities, sleep, and functionality. Results: Patients presented different somatosensory patterns, but no specific subgroups regarding sensory signs and psychological features were detected. Hypersensitivity for noxious mechanical and thermal stimuli and hyposensitivity for nonnoxious mechanical stimuli were the most prominent features. Thirty-one percent of patients showed signs of central sensitization as indicated by abnormally increased pinprick hyperalgesia or dynamic mechanical allodynia. Central sensitization was associated with higher pain intensities (P < 0.001). Only a small influence of psychiatric comorbidities on mechanical pain sensitivity (P = 0.044) and vibration detection (P = 0.028) was found, which was partly associated with high pain intensities. A small subgroup of patients (11.4%) demonstrated thermal hyposensitivity (loss of small-fiber function). Conclusion: Patients with FMS showed various somatosensory abnormalities. These were not significantly influenced by psychological comorbidities. Signs for central sensitization were detected in about one-third of patients and associated with higher pain intensities. This supports the notion of central sensitization being a major pathophysiological mechanism in FMS, whereas small-fiber loss may be less important.

PREDICT will undertake analytical validation of a peak alpha frequency and corticomotor excitability biomarker, determining the sensitivity, specificity, and accuracy at predicting pain sensitivity., Introduction: Temporomandibular disorder is a common musculoskeletal pain condition with development of chronic symptoms in 49% of patients. Although a number of biological factors have shown an association with chronic temporomandibular disorder in cross-sectional and case control studies, there are currently no biomarkers that can predict the development of chronic symptoms. The PREDICT study aims to undertake analytical validation of a novel peak alpha frequency (PAF) and corticomotor excitability (CME) biomarker signature using a human model of the transition to sustained myofascial temporomandibular pain (masseter intramuscular injection of nerve growth factor [NGF]). This article describes, a priori, the methods and analysis plan. Methods: This study uses a multisite longitudinal, experimental study to follow individuals for a period of 30 days as they progressively develop and experience complete resolution of NGF-induced muscle pain. One hundred fifty healthy participants will be recruited. Participants will complete twice daily electronic pain diaries from day 0 to day 30 and undergo assessment of pressure pain thresholds, and recording of PAF and CME on days 0, 2, and 5. Intramuscular injection of NGF will be given into the right masseter muscle on days 0 and 2. The primary outcome is pain sensitivity. Perspective: PREDICT is the first study to undertake analytical validation of a PAF and CME biomarker signature. The study will determine the sensitivity, specificity, and accuracy of the biomarker signature to predict an individual's sensitivity to pain. Registration details: ClinicalTrials.gov: NCT04241562 (prospective).

Introduction:. Hydroxyurea (HU) is a drug that targets the underlying pathophysiology of sickle cell disease (SCD); however, it continues to be an underutilized treatment for adults. Previous research suggests that HU treatment can result in fewer hospital contacts for acute vaso-occlusive pain crises (VOC). Hydroxyurea's impact on non-VOC pain, however, is not well established. Objectives:. This study examined whether HU moderated patterns of static and dynamic pain processing and clinical pain in SCD individuals. Methods:. Fifty-eight patients with SCD (N taking HU = 17) underwent quantitative sensory testing (QST) and completed twice daily symptom diaries for 12 weeks. Quantitative sensory testing established thermal threshold and tolerance, mechanical thresholds, and thermal and mechanical temporal summation of pain. Results:. Groups did not differ in age, sex, or opioid use. After controlling for morphine use, QST results showed that participants taking HU had higher heat and mechanical pain thresholds (static QST measures) but not thermal and mechanical temporal summation (dynamic QST measures). Participants taking HU also reported lower VOC pain compared with SCD participants not taking HU; however, HU did not moderate non-VOC clinical pain ratings. Conclusion:. Findings cautiously suggest that HU acts on pain hypersensitivity and VOC pain, rather than inhibiting pain facilitation and non-VOC pain. These differences may reflect HU's influence on peripheral rather than central sensitization. Future research is warranted to replicate these findings in a larger sample and determine whether early HU administration can prevent peripheral sensitization in SCD individuals.

High-frequency stimulation of the skin induces secondary pinprick hyperalgesia but does not affect pressure pain thresholds either locally or at more distant body sites., Introduction: An increasing number of clinical studies involving a range of chronic pain conditions report widespread mechanical pressure pain hypersensitivity, which is commonly interpreted as resulting from central sensitization (CS). Secondary hyperalgesia (increased pinprick sensitivity surrounding the site of injury) is considered to be a manifestation of CS. However, it has not been rigorously tested whether CS induced by peripheral nociceptive input involves widespread mechanical pressure pain hypersensitivity. Objectives: The aim of this study was to assess whether high-frequency electrical stimulation (HFS), which induces a robust secondary hyperalgesia, also induces a widespread decrease of pressure pain thresholds (PPTs). Methods: We measured PPTs bilaterally on the temples (temporalis muscles), on the legs (tibialis anterior muscles), and on the ventral forearm (flexor carpi radialis muscles) before, 20 minutes after, and 45 minutes after applying HFS on the ventral forearm of sixteen healthy young volunteers. To evaluate the presence of secondary hyperalgesia, mechanical pinprick sensitivity was assessed on the skin surrounding the site where HFS was applied and also on the contralateral arm. Results: HFS induced a significant increase in mechanical pinprick sensitivity on the HFS-treated arm. However, HFS did not decrease PPTs neither in the area of increased pinprick sensitivity nor at more distant sites. Conclusion: This study provides no evidence for the hypothesis that CS, induced after intense activation of skin nociceptors, involves a widespread decrease of PPTs.

A retrospective review of 3,265,894 veterans seen over a 5-year period demonstrates dry eye is associated with numerous chronic pain conditions implying shared mechanisms., Introduction: Recent evidence suggests that dry eye (DE) may be comorbid with other chronic pain conditions. Objectives: To evaluate DE as a comorbid condition in the U.S. veteran population. Methods: Retrospective review of veterans seen in the Veterans Administration Healthcare System (Veteran Affairs) between January 1, 2010, and December 31, 2014. Dry eye and nonocular pain disorders were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. Dry eye was further separated into ICD-9 codes representing tear film dysfunction or ocular pain. χ2 and logistic regression analyses were used to examine frequency and risk of DE, ocular pain, and tear film dysfunction by pain disorders. Results: Of 3,265,894 veterans, 959,881 had a DE diagnosis (29.4%). Dry eye frequency increased with the number of pain conditions reported (P < 0.0005). Ocular pain was most strongly associated with headache (odds ratio [OR] 2.98; 95% confidence interval [CI] 2.95–3.01), tension headache (OR 2.64; 95% CI 2.58–2.71), migraine (OR 2.58; 95% CI 2.54–2.61), temporomandibular joint dysfunction (OR 2.39; 95% CI 2.34–2.44), pelvic pain (OR 2.30; 95% CI 2.24–2.37), central pain syndrome (OR 2.24; 95% CI 1.94–2.60), and fibromyalgia/muscle pain (OR 2.23; 95% CI 2.20–2.26), all P < 0.0005. Tear film dysfunction was most closely associated with osteoarthritis (OR 1.97; 95% CI 1.96–1.98) and postherpetic neuralgia (OR 1.95; 95% CI 1.90–2.00), both P < 0.0005. Conclusions: Dry eye, including both ocular pain and tear film dysfunction, is comorbid with pain conditions in this nationwide population, implying common mechanisms.

Analysis of a nationwide sample of patients with low back pain shows an association between depression and higher rates of opioid prescribing., Introduction: Low back pain (LBP) is among the leading indications for the prescription of opioid analgesics in clinical practice. There is increasing evidence suggesting that these agents may have diminished efficacy in the treatment of LBP. Objectives: We evaluated the relationship between depression, the probability of receiving an opioid prescription, and the amount of morphine equivalent amounts prescribed per year among patients with LBP using nationwide data. Methods: A cross-sectional analysis was performed on existing data from the Medical Expenditure Panel Survey data set from the period 2004 to 2009. Demographic, medical condition, Patient Health Questionnaire-2 responses, and prescription drug information were obtained on 56,811,864 weighted person-years of data from individuals aged 18 to 65 with an ICD-9 code specific to LBP. Results: Increases in PHQ-2 score, as well a positive screen for depression, were associated with an increased probability of being prescribed opioid therapy and more morphine equivalents per year. Conclusion: Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy.

Supplemental Digital Content is Available in the Text. The phonetic parameters of loudness and pitch can separate nociceptive sensations from thermoceptives ones, which might qualify the 2 parameters as nonverbal pain indicators., Introduction and Objectives: There have, yet, been only few attempts to phonetically characterize the vocalizations of pain, although there is wide agreement that moaning, groaning, or other nonverbal utterance can be indicative of pain. We studied the production of vowels “u,” “a,” “i”, and “schwa” (central vowel, sounding like a darker “e” as in hesitations like “ehm”)—as experimental approximations to natural vocalizations. Methods: In 50 students vowel production and self-report ratings were assessed during painful and nonpainful heat stimulation (hot water immersion) as well as during baseline (no-stimulation). The phonetic parameters extracted were pitch (mean F0), phonatory fluctuations (range F0) and loudness (acoustic energy level). Results: Only for the vowels “u” and “schwa,” which might be considered best approximations to moaning and groaning, did pitch and loudness increase during pain. Furthermore, changes from nonpainful to painful stimulations in these parameters also significantly predicted concurrent changes in pain ratings. Conclusion: Vocalization characteristics of pain seem to be best described by an increase in pitch and in loudness. Future studies using more specific and comprehensive phonetic analyses will surely help to provide an even more precise characterization of vocalizations because of pain.

Patients who reported significant medication-related side effects reported greater activity interference, negative affect, catastrophizing, and opioid misuse risk compared with those with fewer side effects., Background: There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Methods: Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Results: Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects (P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk (P < 0.001). Discussion: This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.

The current IASP definition of pain has come under renewed criticisms recently. There is a new momentum for its revision as reflected by the fact that IASP has now a Presidential Task Force dedicated to look into whether there is enough warrant to update the definition. I critically review all the major criticisms of the current definition in detail, and raise new difficulties rarely discussed before. I show that none of the major criticisms has enough warrant to force us to substantially revise the current definition. Combined with the discussion of the new difficulties, there is nonetheless a need to restate the definition using slightly different terminology that will make the original intent of the current definition clearer and more precise. A restatement of the definition is proposed and its potential is discussed in light of some empirical questions that remain.

Introduction:. Chronic pain patients frequently report having sleep disturbances and many tend to stay up during the night and then sleep into the day. Objectives:. This study was designed to compare a heterogeneous group of persons with chronic pain who reported typically going to bed between the hours of 9 pm and midnight with those who go to bed at other hours of the day and night. Methods:. Two hundred seventy-nine participants were divided between those who reported going to bed between the hours of 9 pm and midnight (N = 205) and those who reported having atypical bedtimes (N = 74) based on pre–post questionnaire data and average pain assessments from a smartphone pain application (app). Results:. Those individuals in the atypical bedtime group reported waking up more frequently and getting fewer hours sleep (P < 0.05). These individuals also reported significantly higher pain scores, activity interference, and taking more prescription opioid medication compared with those who had typical bedtimes (P < 0.05). Based on average 3-month daily assessments, those subjects with an atypical bedtime consistently reported more sleep disturbances, pain, activity interference, negative mood, and general worsening conditions over time, and elevated pain catastrophizing, pain-related disability, emotional distress scores, and more prescription medication for pain at 3-month follow-up (P < 0.01). Conclusion:. These results support the importance of providers asking patients with pain about what time they typically go to bed at night to gain a greater understanding of their lifestyle habits. Future studies are needed to further determine the importance of maintaining a typical bedtime among patients with chronic pain.

Supplemental Digital Content is Available in the Text., Background: Chronic facial pain often overlaps with pain experienced elsewhere in the body, although previous studies have focused on a few, selected pain conditions when assessing the degree of overlap. Aim: To quantify the degree of overlap between facial pain and pain reported at multiple locations throughout the body. Methods: Data were from a case–control study of US adults participating in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) project. They were interviewed to determine the presence of chronic facial pain (n = 424 cases) or its absence (n = 912 controls). A mailed questionnaire with a body drawing asked about pain at other locations. Odds ratios (ORs) and 95% confidence limits (95% CLs) quantified the degree of overlap between facial pain and pain at other locations. For replication, cross-sectional data were analyzed from the UK Biobank study (n = 459,604 participants) and the US National Health Interview Survey (n = 27,731 participants). Results: In univariate analysis, facial pain had greatest overlap with headache (OR = 14.2, 95% CL = 9.7–20.8) followed by neck pain (OR = 8.5, 95% CL = 6.5–11.0), whereas overlap decreased substantially (ORs of 4.4 or less) for pain at successively remote locations below the neck. The same anatomically based ranking of ORs persisted in multivariable analysis that adjusted for demographics and risk factors for facial pain. Findings were replicated in the UK Biobank study and the US National Health Interview Survey. The observed anatomical selectivity in the degree of overlap could be a consequence of neurosensory and/or affective processes that differentially amplify pain according to its location.

Introduction:. Increase in excitability of the primary motor cortex (M1) is associated with pain inhibition by analgesics, which is, in turn, associated with the psychophysical antinociceptive pain modulation profile. However, the relationship between neurophysiological M1 excitability and psychophysical pain modulation has not yet been explored. Objectives:. We aim to study these relationships in healthy subjects. Methods:. Forty-one young healthy subjects (22 women) underwent a wide battery of psychophysical testing that included conditioned pain modulation (CPM) and pain temporal summation, and a transcranial magnetic stimulation neurophysiological assessment of the motor corticospinal excitability, including resting motor threshold, motor-evoked potentials (MEPs), and cortical silent period. Results:. Increased motor corticospinal excitability in 2 parameters was associated with more efficient CPM: (1) higher MEP amplitude (r = −0.574; P_Bonferroni = 0.02) and (2) longer MEP duration (r = −0.543; P_Bonferroni = 0.02). The latter also correlated with the lower temporal summation magnitude (r = −0.421; P = 0.007); however, on multiplicity adjustment, significance was lost. Conclusions:. Increased corticospinal excitability of the primary motor cortex is associated with more efficient inhibitory pain modulation as assessed by CPM, in healthy subjects. Motor-evoked potential amplitude and duration may be considered as an additional, objective and easy to measure parameter to allow for better individual assessment of pain modulation profile.

Genotyping-based treatment decisions optimize care and reduce costs through lower medication utilization and fewer adverse events. Genotyping should be considered for patients with chronic pain., Introduction: Genotyping-based treatment decisions may optimize treatment response and minimize adverse drug events (ADEs) in patients with chronic pain. Objectives: To estimate the financial impact of genotyping-based treatment decisions in patients with moderate to severe chronic pain in a managed care setting. Methods: A budget impact model was built with a 1-year time horizon to estimate costs of genotyping-based treatment decisions in a 1000-patient cohort. The model includes drug costs, type and cost of ADEs, distribution of treatments used, and genotyping costs. Event rates and health care costs were derived from primary literature. Three patient cohorts were assessed with and without genotyping-based treatment decisions: no genetic testing; 50% genetic testing; and 100% genetic testing. Sensitivity analysis was performed varying costs, adherence, and the percentage of patients treated according to genotyping results. Results: Medical and ADE costs varied by patient severity and genotyping rates. Without genotyping, drug and ADE costs ranged from $1,544,377 to $24,313,844. With genotyping-based treatment, total costs ranged from $1,780,922 to $18,868,032. Sensitivity analysis, varying costs, adherence, and genotyping rates suggested genotyping improves outcomes and is cost saving in patients with chronic pain. Conclusion: Genotyping-based treatment costs are offset by reduced medication utilization and adverse event costs. Genotyping should be considered for patients with chronic pain in clinical practice and within clinical trials.

This pilot study provides evidence supporting the feasibility and validity of new self-report methodology for the assessment of rest vs evoked pain in chronic neuropathic conditions. Future confirmatory studies will further expand this field and facilitate important improvements in the research and development of new treatments for chronic pain., Introduction: The distinction between pain at rest and pain evoked by touch or movement has important clinical implications and may be associated with different mechanisms. However, current methods of clinical pain assessment pay little attention to directly distinguishing between these contrasting components of symptom burden. Objectives: We developed the 10-item “Functional Impact of Neuropathic Evoked and Spontaneous Symptom Evaluation” questionnaire designed to distinguish between rest and evoked pain. Methods: A prospective observational pilot study of this questionnaire was conducted in 78 participants with neuropathic pain diagnoses. Other study measures included the self-report version of the Leeds Assessment of Neuropathic Symptoms and Signs questionnaire and a modified Brief Pain Inventory. Exploratory analyses were conducted to evaluate the validity of the Functional Impact of Neuropathic Evoked and Spontaneous Symptom Evaluation questionnaire. Results: Pain symptoms often/very often/always (1) evoked by touch or movement, and (2) occurring at rest without tactile stimulation were reported by 81% and 65%, respectively. Evoked pain was associated with walking (64%) and standing (35%); and rest pain was associated with watching television (47%), reading (37%), and sitting (36%). Participants reporting both rest and evoked pain tended to report higher levels of pain interference compared to those reporting evoked pain only. Discussion: These results provide support for the feasibility and validity of new patient-report methods to distinguish between rest pain and evoked pain in chronic neuropathic conditions. Future studies are needed to confirm the reliability and validity of these methods, which may facilitate important improvements in the research and development of new treatments for chronic pain.