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Background/objectives: Chronic pain is an opioid use disorder (OUD) treatment barrier and associated with poor outcomes in OUD treatment including relapse. Fibromyalgia is a chronic pain condition related to central nervous system substrates that overlap with the brain disease model of OUD. We know of no studies that have looked at non-treatment seeking individuals, to see if fibromyalgia might represent a barrier to OUD treatment. Given many non-treatment-seeking individuals previously attempted recovery before experiencing relapse, and chronic pain is a known precipitant of relapse, fibromyalgia might be a currently unappreciated modifiable factor in OUD relapse and, potentially, a barrier to treatment reengagement among those not currently seeking treatment. This study aimed to determine if fibromyalgia is associated with greater odds of agreeing that 'I have tried to stop using opioids before, but pain caused me to relapse' among non-treatment seeking individuals with OUD., Methods: This cross-sectional study recruited non-treatment-seeking individuals with OUD ( n  = 141) from a syringe service program. Ordinal logistic regression was used to determine if the presence of fibromyalgia increased the odds of agreement with prior pain-precipitated relapse., Results: Fibromyalgia was identified in 35% of study participants and associated with 125% greater odds of strongly agreeing that pain had previously caused them to relapse, even after accounting for relevant covariates, including age, sex, depression, anxiety, OUD severity, and pain severity., Conclusions: This study provides early evidence that the presence of fibromyalgia may be associated with increased odds of pain-precipitated OUD relapse.

Background: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC)., Methods: We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance)., Discussion: Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans., Trial Registration: This protocol is registered at clinicaltrials.gov under study number NCT06213233., (© 2024. The Author(s).)

Purpose: In patients with urologic chronic pelvic pain syndrome (UCPPS), the presence of widespread pain appears to identify a distinct phenotype, with a different symptom trajectory and potentially different response to treatment than patients with pelvic pain only., Materials and Methods: A 76-site body map was administered four times, at weekly intervals, to 568 male and female UCPPS participants in the MAPP Network protocol. The 76 sites were classified into 13 regions (1 pelvic region and 12 nonpelvic regions). The degree of widespread pain was scored from 0 to 12 based on the number of reported nonpelvic pain regions. This continuous body map score was regressed over other measures of widespread pain, with UCPPS symptom severity, and with psychosocial variables to measure level of association. These models were repeated using an updated body map score (0-12) that incorporated a threshold of pain ≥ 4 at each site., Results: Body map scores showed limited variability over the 4 weekly assessments, indicating that a single baseline assessment was sufficient. The widespread pain score correlated highly with other measures of widespread pain and correlated with worsened UCPPS symptom severity and psychosocial functioning. Incorporating a pain severity threshold ≥4 resulted in only marginal increases in these correlations., Conclusions: These results support the use of this 13-region body map in the baseline clinical assessment of UCPPS patients. It provides reliable data about the presence of widespread pain and does not require measurement of pain severity, making it relatively simple to use for clinical purposes., (© 2024 The Authors. Neurourology and Urodynamics published by Wiley Periodicals LLC.)

Objectives: Cannabis is increasingly being used for chronic pain management, but cannabis' effects remain poorly characterized in chronic nociplastic pain (NPP), which is posited to be caused by disturbances in nervous system pain processing. In this cross-sectional study (n=1213), we used the 2011 Fibromyalgia (FM) Survey Criteria as a surrogate measure for degree of NPP among individuals using medical cannabis for chronic pain., Methods: Using a quartile-split, we investigated associations between the degree of NPP and medication use, cannabis use characteristics, and symptom relief. Continuous variables were assessed using one-way analysis of variance and categorical variables with Pearson χ 2 test and binomial logistic regression for calculation of odds ratios., Results: Participants were predominately female (59%), with a mean ± SD age of 49.4±13.6 years. Higher FM scores were associated with less self-reported improvement in pain and health since initiating medical cannabis use, as well as more cannabis-related side effects. Paradoxically, higher FM scores were also associated with higher usage of concomitant medication use (including opioids and benzodiazepines) but also with substituting cannabis for significantly more medication classes, including opioids and benzodiazepines., Discussion: This article presents evidence that individuals in higher NPP quartiles have higher analgesic intake, higher odds of substituting cannabis for medications, higher side effect burden, and lower therapeutic effect from cannabis. These seemingly contradictory findings may reflect higher symptom burden, polypharmacy at baseline, or that NPP may be challenging to treat with cannabis. Further research is necessary to further explain cannabinoid effects in NPP., Competing Interests: K.F.B. sits on a Data Safety and Monitoring Committee for Vireo Health (unpaid). D.A.W. has consulted for Swing Therapeutics, Inc., and Community Health Focus, Inc. E.L. is Chief Medical Officer at and co-owner of Om of Medicine, a medical cannabis provisioning center in Ann Arbor, MI. S.S. leads the Scottsdale Research Institute, has received funding from the Multidisciplinary Association for Psychedelic Studies, and is a member of the Steering Committee/Entrepreneurship and Social Initiative Impact Advisor Board for the Lambert Center for the Study of Medicinal Cannabis and Hemp. D.J.C. has consulted for Pfizer, Inc., Eli Lilly and Co., Tonix Pharmaceuticals, Aptinyx, Regeneron, IMC, and Intec. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Ten Chronic Overlapping Pain Conditions (COPCs) are currently recognized by the National Institutes of Health Pain Consortium (eg, irritable bowel syndrome, chronic migraine headache, and chronic low back pain). These conditions affect millions of Americans; however, assessing these conditions, their co-occurrence, and their relationship to treatment has proven challenging due to time constraints and a lack of standardized measures. We present a Chronic Overlapping Pain Condition-Screener (COPC-S) that is logic-driven, efficient, and freely available in electronic format to nonprofit entities. Thirty experts were convened to identify and modify self-report criteria for each COPC as well as criteria that trigger the administration of the diagnostic criteria from a body map and a brief series of questions. Their recommendations were then programmed into the Research Electronic Data Capture platform and refined for comprehensibility and ease of use by patient focus groups. The electronic screener and physician-administered criteria were both administered to patients with known COPCs in a counter-balanced fashion to determine the level of agreement between methods. The expert panel identified screening items/body map regions and diagnostic criteria for all 10 COPCs. Patients found the content comprehensible and the platform easy to use. Cohen's Kappa statistics suggested good agreement between the electronic COPC-S and criteria administered by a physician (κ = .813). The COPC-S is an efficient tool for screening multiple COPCs and has applicability to research studies, clinical trials, and clinical practice. PERSPECTIVE: Assessing COPCs remains a challenge for researchers and clinicians. The COPC-S is an efficient and logic-driven electronic tool that allows for the rapid screening assessment of 10 COPCs. The instrument may have utility in research and clinical settings., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Chronic pain has economic costs on par with cardiovascular disease, diabetes, and cancer. Despite this impact on the health care system and increasing awareness of the relationship between pain and mortality, efforts to identify simple symptom-based risk factors for the development of pain, particularly in children, have fallen short. This is critically important as pain that manifests during childhood often persists into adulthood. To date, no longitudinal studies have examined symptoms in pain-free children that presage a new, multisite manifestation of pain in the future. We hypothesized that female sex, sleep problems, and heightened somatic symptoms complaints at baseline would be associated with the risk of developing new multisite pain 1 year later., Methods: Symptom assessments were completed by parents of youth (ages 9 to 10) enrolled in the Adolescent Brain Cognitive Development study. Multivariate logistic regression models focused on children who developed multisite pain 1 year later (n=331) and children who remained pain free (n=3335)., Results: Female sex (odds ratio [OR]=1.35; 95% CI, 1.07, 1.71; P =0.01), elevated nonpainful somatic symptoms (OR=1.17; 95% CI, 1.06, 1.29; P <0.01), total sleep problems (OR=1.20; 95% CI, 1.07, 1.34; P <0.01), and attentional issues (OR=1.22; 95% CI, 1.10, 1.35; P <0.001) at baseline were associated with new multisite pain 1 year later. Baseline negative affect was not associated with new multisite pain., Discussion: Identifying symptom-based risk factors for multisite pain in children is critical for early prevention. Somatic awareness, sleep and attention problems represent actionable targets for early detection, treatment, and possible prevention of multisite pain in youth., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Chronic pain affects more than 50 million Americans. Treatments remain inadequate, in large part, because the pathophysiological mechanisms underlying the development of chronic pain remain poorly understood. Pain biomarkers could potentially identify and measure biological pathways and phenotypical expressions that are altered by pain, provide insight into biological treatment targets, and help identify at-risk patients who might benefit from early intervention. Biomarkers are used to diagnose, track, and treat other diseases, but no validated clinical biomarkers exist yet for chronic pain. To address this problem, the National Institutes of Health Common Fund launched the Acute to Chronic Pain Signatures (A2CPS) program to evaluate candidate biomarkers, develop them into biosignatures, and discover novel biomarkers for chronification of pain after surgery. This article discusses candidate biomarkers identified by A2CPS for evaluation, including genomic, proteomic, metabolomic, lipidomic, neuroimaging, psychophysical, psychological, and behavioral measures. Acute to Chronic Pain Signatures will provide the most comprehensive investigation of biomarkers for the transition to chronic postsurgical pain undertaken to date. Data and analytic resources generatedby A2CPS will be shared with the scientific community in hopes that other investigators will extract valuable insights beyond A2CPS's initial findings. This article will review the identified biomarkers and rationale for including them, the current state of the science on biomarkers of the transition from acute to chronic pain, gaps in the literature, and how A2CPS will address these gaps., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Evidence-based treatments for chronic low back pain (cLBP) typically work well in only a fraction of patients, and at present there is little guidance regarding what treatment should be used in which patients. Our central hypothesis is that an interventional response phenotyping study can identify individuals with different underlying mechanisms for their pain who thus respond differentially to evidence-based treatments for cLBP. Thus, we will conduct a randomized controlled Sequential, Multiple Assessment, Randomized Trial (SMART) design study in cLBP with the following three aims. Aim 1: Perform an interventional response phenotyping study in a cohort of cLBP patients (n = 400), who will receive a sequence of interventions known to be effective in cLBP. For 4 weeks, all cLBP participants will receive a web-based pain self-management program as part of a run-in period, then individuals who report no or minimal improvement will be randomized to: a) mindfulness-based stress reduction, b) physical therapy and exercise, c) acupressure self-management, and d) duloxetine. After 8 weeks, individuals who remain symptomatic will be re-randomized to a different treatment for an additional 8 weeks. Using those data, we will identify the subsets of participants that respond to each treatment. In Aim 2, we will show that currently available, clinically derived measures, can predict differential responsiveness to the treatments. In Aim 3, a subset of participants will receive deeper phenotyping (n = 160), to identify new experimental measures that predict differential responsiveness to the treatments, as well as to infer mechanisms of action. Deep phenotyping will include functional neuroimaging, quantitative sensory testing, measures of inflammation, and measures of autonomic tone., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine.)

Exploring the relationship between nociplastic pain and the severity and impact of pelvic pain symptoms could lend insight into the heterogeneous symptom presentation and treatment response that complicates management of chronic pelvic pain. In this prospective cross-sectional study, we sought to evaluate relationships between degree of nociplastic pain, measured by the Fibromyalgia (FM) Survey Score, and multiple aspects of the chronic pelvic pain (CPP) experience, including severity, frequency, tenderness during pelvic myofascial exam, interference with daily life, and high-impact pain. The study included 303 women who presented to a tertiary referral clinic for chronic pelvic pain and endometriosis. Multiple measures of pelvic pain, including pain severity, frequency, interference, pelvic myofascial pain, and high-impact pain were examined in General Linear Models with FM Survey Score as the primary predictor of interest in models controlling for endometriosis, surgical history, use of opioids, body mass index, and patient age. Higher level of nociplastic pain was associated with greater pelvic pain severity, frequency, interference, and pelvic myofascial pain (all P < .05). For all models, degree of nociplastic pain was more strongly associated with pain outcomes than the presence of endometriosis, and use of opioids was the only stronger predictor of worse pain outcomes. The likelihood of high impact pain increased 7% for each additional point on the FM Survey Score. Degree of nociplastic pain was robustly associated with severity, frequency, and impact of pelvic pain, and was independent of the presence of endometriosis, history of surgical procedures for pelvic pain, age, and BMI. Trial registration: not applicable PERSPECTIVE: This article evaluates the impact of nociplastic pain on symptoms and functional status in chronic pelvic pain. These findings raise the possibility that a simple screening tool for nociplastic pain might provide clinically actionable information without the need for deep neurobiological phenotyping and may inform development of personalized management strategies., (Copyright © 2023 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Fibromyalgia is characterized by chronic widespread pain, mood, and sleep disturbance. Pharmacological treatments have modest efficacy and are associated with negative side effects, and alternative approaches are needed. Morning bright light treatment may assist in the management of fibromyalgia as it can reduce depressive symptoms, improve sleep, and advance circadian timing., Methods: Sixty people with fibromyalgia (58 women, mean age 41.8 ± 13.3 years) were enrolled in a study comparing 4 weeks of a 1-hour daily morning bright light treatment (active treatment) to a morning dim light treatment (comparison treatment). Both light treatments included behavioral procedures to stabilize sleep timing. The morning bright light treatment was expected to produce larger improvements in pain and function than the dim light treatment and larger improvements in potential mediators (mood, sleep, and circadian timing)., Results: Both the bright and dim light treatment groups achieved significant but similar levels of improvement in pain intensity, pain interference, physical function, depressive symptoms, and sleep disturbance. Overall, the sample on average displayed a clinically meaningful improvement in the Fibromyalgia Impact Questionnaire-Revised score (mean reduction of 11.2 points), comparable to that reported following physical exercise treatments. Minimal side effects were observed., Conclusions: Findings indicate that the effects of a morning bright light treatment did not exceed those of a comparison dim light treatment; yet the changes on average in both conditions revealed clinically meaningful improvements. Future research is warranted to identify what elements of this trial may have contributed to the observed effects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Abstract: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a common and debilitating disease with poor treatment outcomes. Studies from the multidisciplinary approach to the study of chronic pelvic pain research network established that IC/BPS patients with chronic overlapping pain conditions (COPCs) experience poorer quality of life and more severe symptoms, yet the neurobiological correlates of this subtype are largely unknown. We previously showed that ex vivo toll-like receptor 4 (TLR4) cytokine/chemokine release is associated with the presence of COPCs, as well as widespread pain and experimental pain sensitivity women with IC/BPS. Here, we attempt to confirm these findings in the multisite multidisciplinary approach to the study of chronic pelvic pain Symptom Patterns Study using TLR4-stimulated whole blood (female IC/BPS patients with COPC n = 99; without n = 36). Samples were collected in tubes preloaded with TLR4 agonist, incubated for 24 hours, and resulting supernatant assayed for 7 cytokines/chemokines. These were subject to a principal components analysis and the resulting components used as dependent variables in general linear models. Controlling for patient age, body mass index, and site of collection, we found that greater ex vivo TLR4-stimulated cytokine/chemokine release was associated with the presence of COPCs ( P < 0.01), extent of widespread pain ( P < 0.05), but not experimental pain sensitivity ( P > 0.05). However, a second component of anti-inflammatory, regulatory, and chemotactic activity was associated with reduced pain sensitivity ( P < 0.01). These results confirm that the IC/BPS + COPCs subtype show higher levels of ex vivo TLR4 cytokine/chemokine release and support a link between immune priming and nociplastic pain in IC/BPS., (Copyright © 2022 International Association for the Study of Pain.)

Abstract: Dysmenorrhea is characterized by high rates of transition to chronic pain. In a previous study using structural equation modeling, we demonstrated that several symptom domains associated with the emerging concept of nociplastic pain can be described using 2 symptom groups: generalized sensory sensitivity (GSS; composed of widespread pain, interceptive sensitivity, and environmental sensitivity) and SPACE (composed of unrefreshing sleep, pain, affective disturbances, cognitive issues, and reduced energy). Here, we perform a secondary cross-sectional analysis examining the same symptoms groups in a cohort of patients with dysmenorrhea without a diagnosis of chronic pain. Our purpose is to determine if the same symptom patterns are apparent and if they are associated with the presence and severity of comorbid pain. Participants were 201 women with dysmenorrhea. We replicated the hypothesized 2-factor structure in this cohort (comparative fit index = 0.971 and root mean square error of approximation =0.055; 90% CI: 0.000-0.097). Generalized sensory sensitivity was associated with the severity of bladder, bowel, and overall pain in multivariable models including SPACE, patient age, and BMI (all β > 0.32, all P < 0.05). Sleep, pain, affective disturbances, cognitive issues, and reduced energy were associated with menstrual pain during nonsteroidal anti-inflammatory drug use, whereas GSS was associated with the same in the absence of nonsteroidal anti-inflammatory drug use (both P < 0.05). This 2-factor model of symptoms seems to be replicable and valid in a cohort of women at risk for developing chronic pain conditions. These symptom groups are promising potential markers of future pain chronification and may point to patients in need of earlier or more aggressive intervention., (Copyright © 2022 International Association for the Study of Pain.)

Chronic pain is highly prevalent in patients with cirrhosis and is associated with poor health-related quality of life and poor functional status. However, there is limited guidance on appropriate pain management in this population, and pharmacologic treatment can be harmful, leading to adverse outcomes, such as gastrointestinal bleeding, renal injury, falls, and hepatic encephalopathy. Chronic pain can be categorized mechanistically into three pain types: nociceptive, neuropathic, and nociplastic, each responsive to different therapies. By discussing the identification, etiology, and treatment of these three mechanistic pain descriptors with a focus on specific challenges in patients with cirrhosis, we provide a framework for better tailoring treatments, including nonpharmacologic therapies, to patients' needs., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Importance: Cognitive behavioral therapy for chronic pain (CBT-CP) is a safe and effective alternative to opioid analgesics. Because CBT-CP requires multiple sessions and therapists are scarce, many patients have limited access or fail to complete treatment., Objectives: To determine if a CBT-CP program that personalizes patient treatment using reinforcement learning, a field of artificial intelligence (AI), and interactive voice response (IVR) calls is noninferior to standard telephone CBT-CP and saves therapist time., Design, Setting, and Participants: This was a randomized noninferiority, comparative effectiveness trial including 278 patients with chronic back pain from the Department of Veterans Affairs health system (recruitment and data collection from July 11, 2017-April 9, 2020). More patients were randomized to the AI-CBT-CP group than to the control (1.4:1) to maximize the system's ability to learn from patient interactions., Interventions: All patients received 10 weeks of CBT-CP. For the AI-CBT-CP group, patient feedback via daily IVR calls was used by the AI engine to make weekly recommendations for either a 45-minute or 15-minute therapist-delivered telephone session or an individualized IVR-delivered therapist message. Patients in the comparison group were offered 10 therapist-delivered telephone CBT-CP sessions (45 minutes/session)., Main Outcomes and Measures: The primary outcome was the Roland Morris Disability Questionnaire (RMDQ; range 0-24), measured at 3 months (primary end point) and 6 months. Secondary outcomes included pain intensity and pain interference. Consensus guidelines were used to identify clinically meaningful improvements for responder analyses (eg, a 30% improvement in RMDQ scores and pain intensity). Data analyses were performed from April 2021 to May 2022., Results: The study population included 278 patients (mean [SD] age, 63.9 [12.2] years; 248 [89.2%] men; 225 [81.8%] White individuals). The 3-month mean RMDQ score difference between AI-CBT-CP and standard CBT-CP was -0.72 points (95% CI, -2.06 to 0.62) and the 6-month difference was -1.24 (95% CI, -2.48 to 0); noninferiority criterion were met at both the 3- and 6-month end points (P < .001 for both). A greater proportion of patients receiving AI-CBT-CP had clinically meaningful improvements at 6 months as indicated by RMDQ (37% vs 19%; P = .01) and pain intensity scores (29% vs 17%; P = .03). There were no significant differences in secondary outcomes. Pain therapy using AI-CBT-CP required less than half of the therapist time as standard CBT-CP., Conclusions and Relevance: The findings of this randomized comparative effectiveness trial indicated that AI-CBT-CP was noninferior to therapist-delivered telephone CBT-CP and required substantially less therapist time. Interventions like AI-CBT-CP could allow many more patients to be served effectively by CBT-CP programs using the same number of therapists., Trial Registration: ClinicalTrials.gov Identifier: NCT02464449.

Three categories of pain mechanisms are recognized as contributing to pain perception: nociceptive, neuropathic, and nociplastic (ie, central nervous system augmented pain processing). We use validated questionnaires to identify pain mechanisms in Urologic Chronic Pelvic Pain Syndrome (UCCPS) patients (n = 568, female = 378, male = 190) taking part in the Symptom Patterns Study of the Multidisciplinary Approach to the study of chronic Pelvic Pain Research Network. A cutoff score of 12 on the painDETECT questionnaire (-1 to 38) was used to classify patients into the neuropathic category while the median score of 7 on the fibromyalgia survey criteria (0-31) was used to classify patients into the nociplastic category. Categories were compared on demographic, clinical, psychosocial, psychophysical and medication variables. At baseline, 43% of UCPPS patients were classified as nociceptive-only, 8% as neuropathic only, 27% as nociceptive+nociplastic, and 22% as neuropathic+nociplastic. Across outcomes nociceptive-only patients had the least severe symptoms and neuropathic+nociplastic patients the most severe. Neuropathic pain was associated with genital pain and/or sensitivity on pelvic exam, while nociplastic pain was associated with comorbid pain conditions, psychosocial difficulties, and increased pressure pain sensitivity outside the pelvis. A self-report method classifying individuals on pain mechanisms reveals clinical differences that could inform clinical trials and novel targets for treatment. PERSPECTIVE: This article presents differences in clinical characteristics based on a simple self-report method of classifying pain mechanisms for Urologic Chronic Pelvic Pain Syndrome patients. This method can be easily applied to other chronic pain conditions and may be useful for exploring pathophysiology in pain subtypes., (Copyright © 2022. Published by Elsevier Inc.)

Little is known about how individuals with chronic pain use tailored internet-based interventions. This study is the first to compare self-reported skill module use to observed module access and to examine each of these in relationship to tailored recommendations to access specific content. Participants (N = 58) enrolled in a 10-week trial of the Pain EASE program, a tailored internet-based intervention that includes 10 pain self-management skill modules. Participants completed a "Self-Assessment," which was used to provide a "Personalized Plan" that encouraged accessing specific modules. Participants self-reported module use during weekly data collection telephone calls. Program log data were extracted to capture "observed" module use during the trial period. Findings indicated significantly greater self-reported use of the Pain EASE modules compared to observed access with log data. Further, log data revealed that participants accessed less than half of the modules recommended to them via tailoring., (Published by Oxford University Press on behalf of the Society of Behavioral Medicine 2022.)

Abstract: Altered brain structure and function is evident in adults with multisite chronic pain. Although many such adults trace their pain back to childhood, it has been difficult to disentangle whether central nervous system alterations precede or are consequences of chronic pain. If the former is true, aberrant brain activity may identify children vulnerable to developing chronic pain later in life. We examined structural and functional brain magnetic resonance imaging metrics in a subset of children from the first 2 assessments of the Adolescent Brain and Cognitive Development Study. Children (aged 9-10) who were pain free at baseline and then developed multisite pain 1 year later (n = 115) were matched to control children who were pain free at both timepoints (n = 230). We analyzed brain structure (cortical thickness and gray matter volume) and function (spontaneous neural activity and functional connectivity). Results were deemed significant at the cluster level P < 0.05 false discovery rate corrected for multiple comparisons. At baseline, children who subsequently developed multisite pain had increased neural activity in superior parietal /primary somatosensory and motor cortices and decreased activity in the medial prefrontal cortex. They also exhibited stronger functional connectivity between the salience network, somatosensory, and default mode network regions. No significant differences in the brain structure were observed. Increased neural activity and functional connectivity between brain regions, consistent to that seen in adults with chronic pain, exist in children before developing multisite pain. These findings may represent a neural vulnerability to developing future chronic pain., (Copyright © 2021 International Association for the Study of Pain.)

Objective: To examine the impact of educational materials for chronic overlapping pain conditions (COPCs), the feasibility of delivering materials online, and to explore its impact on self-reported self-management applications at 3-month follow-up., Design: Prospective cohort study., Setting: Online., Subjects: Individuals from a university-wide active research repository with ≥1 coded diagnostic COPC by ICD-9/10 in the medical record., Methods: We determined the number of COPCs per participant as indicated by diagnostic codes in the medical record. Consenting participants completed self-report questionnaires and read educational materials. We assessed content awareness and knowledge pre- and post-exposure to education. Comprehension was assessed via embedded questions in reading materials in real time. Participants then completed assessments regarding concept retention, self-management engagement, and pain-related symptoms at 3-months., Results: N = 216 individuals enrolled, with 181 (84%) completing both timepoints. Results indicated that participants understood materials. Knowledge and understanding of COPCs increased significantly after education and was retained at 3-months. Patient characteristics suggested the number of diagnosed COPCs was inversely related to age. Symptoms or self-management application did not change significantly over the 3-month period., Conclusions: The educational materials facilitated teaching of key pain concepts in self-management programs, which translated easily into an electronic format. Education alone may not elicit self-management engagement or symptom reduction in this population; however, conclusions are limited by the study's uncontrolled design. Education is likely an important and meaningful first step in comprehensive COPC self-management., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Internet-based interventions for chronic pain have demonstrated efficacy and may address access barriers to care. Participant characteristics have been shown to affect engagement with these programs; however, limited information is available about the relationship between participant characteristics and engagement with internet-based programs for self-management of chronic pain. The current study examined relationships between demographic and clinical characteristics and engagement with the Pain EASE program, a self-directed, internet-based cognitive behavioral therapy intervention for veterans with chronic low back pain (cLBP). Veterans with cLBP were enrolled in a 10 week trial of the Pain EASE program. Engagement measures included the number of logins, access to coping skill modules, and completed study staff-initiated weekly check-in calls. Regression analyses were conducted to identify significant predictors of engagement from hypothesized predictors (e.g., race/ethnicity, age, depressive symptom severity, and pain interference). Participants (N = 58) were 93% male, 60.3% identified as White, and had a mean age of 54.5 years. Participants logged into the program a median of 3.5 times, accessed a median of 2 skill modules, and attended a median of 6 check-in calls. Quantile regression revealed that, at the 50th percentile, non-White-identified participants accessed fewer modules than White-identified participants (p = .019). Increased age was associated with increased module use (p = .001). No clinical characteristics were significantly associated with engagement measures. White-identified race/ethnicity and increased age were associated with greater engagement with the Pain EASE program. Results highlight the importance of defining and increasing engagement in internet-delivered pain care., (Published by Oxford University Press on behalf of the Society of Behavioral Medicine 2020.)

Cannabidiol (CBD) is widely advertised as helpful for chronic pain management but research is limited. Using a cross-sectional, anonymous survey, we examined patterns of naturalistic CBD use among individuals with fibromyalgia (FM) and other chronic pain conditions. Our objective was to better understand rates of CBD use, reasons for use and discontinuation, communication with healthcare professionals about CBD, and perceptions of CBD effectiveness and safety among people with FM. After excluding incomplete surveys, our study population consisted of N = 2,701 participants with fibromyalgia, primarily in the United States. Overall, 38.1% reported never using CBD, 29.4% reported past CBD use, and 32.4% reported current CBD use. Past-year cannabis use was strongly associated with past or current CBD use. Those using CBD typically did so due to inadequate symptom relief, while those not using CBD typically cited safety concerns as their reason for not using CBD. Two-thirds of participants disclosed CBD use to their physician, although only 33% asked for physician advice on using CBD. Participants used CBD for numerous FM-related symptoms (most commonly pain), and generally reported slight to much improvement across symptom domains. Around half of participants reported side effects, which were typically minor. Our findings are limited by selection bias and our cross-sectional design, which prevents causal associations. In conclusion, CBD use is common among individuals with FM and many individuals using CBD report improvements across numerous FM-related symptoms. Our findings highlight the need for additional rigorous studies to better understand CBD's potential for FM management. PERSPECTIVE: This article indicates that CBD use is common among people with fibromyalgia, and the results suggest that many derive benefit from using CBD across multiple symptoms domains. Clinicians should discuss CBD use with fibromyalgia patients, and future studies are needed to rigorously assess CBD's therapeutic value for fibromyalgia symptoms., (Copyright © 2021 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Abstract: Chronic pain is highly prevalent in multiple sclerosis (MS). Pain heterogeneity may contribute to poor treatment outcomes. The aim of this study was to characterize pain phenotypes distributions in persons with MS and compare pain phenotypes in terms of pain intensity, frequency of chronic overlapping pain conditions, and use and analgesic effects of different classes of pain medications. Data were collected through a national web-based survey with measures of neuropathic (painDETECT) and nociplastic pain (Fibromyalgia Survey Criteria), chronic overlapping pain conditions, and pain medication use and pain relief. In a sample of N = 842 adults with chronic pain and MS, the largest proportion (41%) showed evidence of nociceptive pain, 27% had mixed neuropathic/nociplastic pain, 23% had nociplastic pain, and 9% had neuropathic pain. Nociplastic pain was associated with significantly higher pain intensity and frequency of chronic overlapping pain conditions. Across all pain types, high frequency of pain medication use along with poor-modest pain relief was reported. Cannabis use for pain was more common, and pain relief ratings were higher among those with nociplastic pain, relative to nociceptive pain. Although NSAID use was highest among those with nociplastic pain (80%), pain relief ratings for NSAIDs were highest among those with nociceptive pain. These findings underscore the need for multidimensional assessment of pain in MS with greater emphasis on the identification of pain phenotype. An improved characterization of pain as a multifaceted condition in MS could inform therapeutic approaches., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Aims: The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments., Methods: This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol., Results: Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing., Conclusions: This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions., (© 2020 Wiley Periodicals LLC.)

Objectives: Quantitative sensory testing may help predict treatment responses in individuals with chronic pain. Our objective was to determine whether evoked pain sensitivity at baseline predicted preferential treatment responses to either emotional awareness and expression therapy (EAET) or cognitive behavioral therapy (CBT) in individuals with fibromyalgia (FM)., Methods: This was a secondary analysis of a previous randomized clinical trial, in which individuals with FM were randomized to EAET, CBT, or Education as a control intervention. Only females who completed baseline and post-treatment assessments were analyzed (n=196). The primary outcome was change in overall clinical pain severity from pretreatment to posttreatment, and the primary predictor of interest was pressure pain tolerance at baseline., Results: Among patients with low pain tolerance at baseline (n=154), both EAET and CBT led to small but significant improvements in clinical pain severity (CBT mean=0.66, 95% confidence interval [0.24-1.07]; EAET mean=0.76 [0.34-1.17]). Conversely, in patients with normal pain tolerance (n=42), there was no significant improvement in clinical pain after CBT (0.13 [-0.88 to 1.14]), a small improvement after FM Education (0.81 [0.14-1.48]), but a much larger and statistically significant improvement after EAET (2.14 [1.23-3.04])., Discussion: Normal levels of pressure pain tolerance at baseline predicted greater improvement in clinical pain severity after EAET than CBT. Quantitative sensory testing may provide insights about individual responses to psychologically based therapies for individuals with chronic pain.

Cannabis is widely used for chronic pain. However, there is some evidence of an inverse dose-response relationship between cannabis effects and pain relief that may negatively affect analgesic outcomes. In this cross-sectional survey, we examined whether daily cannabis use frequency was associated with pain severity and interference, quality of life measures relevant to pain (eg, anxiety and depressive symptoms), and cannabis use preferences (administration routes and cannabinoid ratio). Our analysis included 989 adults who used cannabis every day for chronic pain. Participant use was designated as light, moderate, and heavy (1-2, 3-4, and 5 or more cannabis uses per day, respectively). The sample was also subgrouped by self-reported medical-only use (designated MED, n = 531, 54%) versus medical use concomitant with a past-year history of recreational use (designated MEDREC, n = 458, 46%). In the whole sample, increased frequency of use was significantly associated with worse pain intensity and interference, and worse negative affect, although high-frequency users also reported improved positive affect. Subgroup analyses showed that these effects were driven by MED participants. Heavy MED participant consumption patterns showed greater preference for smoking, vaporizing, and high tetrahydrocannabinol products. In contrast, light MED participants had greater preference for tinctures and high cannabidiol products. Selection bias, our focus on chronic pain, and our cross-sectional design likely limit the generalizability of our results. Our findings suggest that lower daily cannabis use frequency is associated with better clinical profile as well as lower risk cannabis use behaviors among MED participants. Future longitudinal studies are needed to examine how high frequency of cannabis use interacts with potential therapeutic benefits. PERSPECTIVE: Our findings suggest that lower daily cannabis use frequency is associated with better clinical profile as well as safer use behaviors (eg, preference for cannabidiol and noninhalation administration routes). These trends highlight the need for developing cannabis use guidelines for clinicians to better protect patients using cannabis., (Copyright © 2019 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To develop and test the feasibility and preliminary efficacy of a cognitive behavioral therapy-based, internet-delivered self-management program for chronic low back pain (cLBP) in veterans., Methods: Phase I included program development, involving expert panel and participant feedback. Phase II was a single-arm feasibility and preliminary efficacy study of the Pain e-health for Activity, Skills, and Education (Pain EASE) program. Feasibility (ie, website use, treatment credibility, satisfaction) was measured using descriptive methods. Mixed models were used to assess mean within-subject changes from baseline to 10 weeks post-baseline in pain interference (primary outcome, West Haven-Yale Multidimensional Pain Inventory, scale of 0 to 6), pain intensity, mood, fatigue, sleep, and depression., Results: Phase I participants (n = 15) suggested modifications including style changes, content reduction, additional "Test Your Knowledge" quizzes, and cognitive behavioral therapy skill practice monitoring form revisions for enhanced usability. In Phase II, participants (n = 58) were mostly male (93%) and White (60%), and had an average age of 55 years (standard deviation [SD] = 12) and moderate pain (mean score 5.9/10); 41 (71%) completed the post-baseline assessment. Participants (N = 58) logged on 6.1 (SD = 8.6) times over 10 weeks, and 85% reported being very or moderately satisfied with Pain EASE. Pain interference improved from a mean of 3.8 at baseline to 3.3 at 10 weeks (difference 0.5 [95% confidence interval 0.1 to 0.9], P = 0.008). Within-subject improvement also occurred for some secondary outcomes, including mood and depression symptoms., Discussion: Veterans with cLBP may benefit from technology-delivered interventions, which may also reduce pain interference. Overall, veterans found that Pain EASE, an internet-based self-management program, is feasible and satisfactory for cLBP., (© 2019 World Institute of Pain.)

Daily fluctuation in pain acceptance and its impact on the physical and psychosocial functioning of individuals living with spinal cord injury (SCI) and chronic pain has not been examined. We used end-of-day diaries and multilevel modeling to examine the moderating effect of within- and between-person pain acceptance on associations between pain and physical and psychosocial functioning. Individuals with SCI and chronic pain (N = 124) completed 7 days of end-of-day diaries, which included measures of pain acceptance, pain intensity, pain catastrophizing, pain interference, participation in social roles and activities, depressive symptoms, and positive affect and well-being. We found within-person variability in pain acceptance (28% of the total variance) and a significant moderating effect of daily fluctuation in pain acceptance on the same-day pain intensity-social roles and activities association. Within-person changes in pain acceptance were also associated with daily changes in pain interference, depressive symptoms, and positive affect and well-being, adjusting for pain intensity and catastrophizing. Findings highlight the potential for daily or momentary assessments of pain acceptance to enhance understanding of how psychological flexibility may contribute to pain-related outcomes. Future studies could further investigate stable and variable characteristics of pain acceptance and their individual contribution to physical and psychosocial functioning. PERSPECTIVE: Daily fluctuations in pain acceptance and their association with physical and psychosocial functioning were observed in the lives of individuals with SCI and chronic pain. These findings may guide future studies to inform the development of effective, pain acceptance-focused individualized treatment approaches for chronic pain management in people with SCI., (Copyright © 2019 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Objectives: Limited research suggests commonalities between urological chronic pelvic pain syndromes (UCPPS) and other nonurological chronic overlapping pain conditions (COPCs) including fibromyalgia, chronic fatigue syndrome, and irritable bowel syndrome. The goal of this case-control study was to examine similarities and differences between UCPPS and these other COPCs., Materials and Methods: As part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research (MAPP) Network, we examined 1039 individuals with UCPPS (n=424), nonurological COPCs (n=200), and healthy controls (HCs; n=415). Validated standardized measures were used to assess urological symptoms, nonurological pain symptoms, and psychosocial symptoms and traits., Results: Participants with UCPPS had more urological symptoms than nonurological COPCs or HCs (P<0.001); nonurological COPC group also had significantly worse urological symptoms than HCs (P<0.001). Participants with nonurological COPCs reported more widespread pain than those with UCPPS (P<0.001), yet both groups had similarly increased symptoms of anxiety, depression, negative affect, perceived stress, neuroticism, and lower levels of extraversion than HCs (P<0.001). Participants with UCPPS with and without COPCs reported more catastrophizing than those with nonurological COPCs (P<0.001)., Discussion: Findings are consistent with the hypothesis of common underlying biopsychosocial mechanisms and can guide the comprehensive assessment and treatment of these conditions regardless of the primary site of pain or diagnosis. Heightened catastrophizing in UCPPS should be examined to inform psychosocial interventions and improve patient care.

Chronic overlapping pain conditions (COPCs) are a set of painful chronic conditions characterized by high levels of co-occurrence. It has been hypothesized that COPCs co-occur in many cases because of common neurobiological vulnerabilities. In practice, most research on COPCs has focused upon a single index condition with little effort to assess comorbid painful conditions. This likely means that important phenotypic differences within a sample are obscured. The International Classification of Diseases (ICD) coding system contains many diagnostic classifications that may be applied to individual COPCs, but there is currently no agreed upon set of codes for identifying and studying each of the COPCs. Here we seek to address this issue through three related projects 1) we first compile a set of ICD-10 codes from expert panels for ten common COPCs, 2) we then use natural language searches of medical records to validate the presence of COPCs in association with the proposed expert codes, 3) finally, we apply the resulting codes to a large administrative medical database to derive estimates of overlap between the ten conditions as a demonstration project. The codes presented can facilitate administrative database research on COPCs. PERSPECTIVE: This article presents a set of ICD-10 codes that researchers can use to explore the presence and overlap of COPCs in administrative databases. This may serve as a tool for estimating samples for research, exploring comorbidities, and treatments for individual COPCs, and identifying mechanisms associated with their overlap., (Copyright © 2019 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Cannabis is commonly used to manage chronic pain, but cannabis use patterns among individuals with chronic pain, has not been well-characterized. We report cannabinoid, administration route, and product selection preferences among medical cannabis users with chronic pain from an ongoing, online survey. We also examined whether these preferences are affected by differences in sex, intentions behind use (medical only [MED] vs medical + recreational [MEDREC]), and experience with cannabis (novice: <1 year vs experienced: ≥1 year). The survey was completed by 1,321 participants (59% female) 76.5% of whom used cannabis every day. 93.4% used 2 or more administration routes and 72.5% used 3 or more. Female, MED, and novice users were less likely to smoke or vaporize (all P < .0001), but more likely to rank edibles, tinctures, and topicals as a first-choice administration route than their counterparts. Female and MED users also preferred low THC: high cannabidiol ratios significantly more than their counterparts. Overall, only 2.6% of participants selected cannabis products with input from a medical professional, although 54.9% relied on advice from dispensary employees. More male, MEDREC, and experienced users selected products based on factors that reflected greater comfort with cannabis (eg, smell, visual properties, cannabis variety). The wide variability in cannabis use among these different groups indicates the need for further research to investigate how specific use routines relate to clinical outcomes. PERSPECTIVE: Medical cannabis users with chronic pain show distinct differences in cannabinoid preferences and administration associated with user sex, intentions behind use, and experience with cannabis. This article highlights the wide variability in cannabis preferences among medical cannabis users with chronic pain, which may be relevant for clinical outcomes., (Copyright © 2019 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Chronic pain is common, costly, and challenging to treat. Many individuals with chronic pain have turned to cannabis as an alternative form of pain management. We report results from an ongoing, online survey of medical cannabis users with chronic pain nationwide about how cannabis affects pain management, health, and pain medication use. We also examined whether and how these parameters were affected by concomitant recreational use, and duration of use (novice: <1 year vs experienced: ≥1 year). There were 1,321 participants (59% female, 54% ≥50 years old) who completed the survey. Consistent with other observational studies, approximately 80% reported substituting cannabis for traditional pain medications (53% for opioids, 22% for benzodiazepines), citing fewer side effects and better symptom management as their rationale for doing so. Medical-only users were older (52 vs 47 years old; P < .0001), less likely to drink alcohol (66% vs 79%, P < .0001), and more likely to be currently taking opioids (21% vs 11%, P < .0001) than users with a combined recreational and medical history. Compared with novice users, experienced users were more likely to be male (64% vs 58%; P < .0001), take no concomitant pain medications (43% vs 30%), and report improved health (74% vs 67%; P = .004) with use. Given that chronic pain is the most common reason for obtaining a medical cannabis license, these results highlight clinically important differences among the changing population of medical cannabis users. More research is needed to better understand effective pain management regimens for medical cannabis users. Perspective: This article presents results that confirm previous clinical studies suggesting that cannabis may be an effective analgesic and potential opioid substitute. Participants reported improved pain, health, and fewer side effects as rationale for substituting. This article highlights how use duration and intentions for use affect reported treatment and substitution effects., (Copyright © 2019 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Current guidelines for addressing opioid cessation in the context of chronic pain management recommend that opioids be discontinued if the risks outweigh the benefits. However, few studies have focused on understanding opioid cessation from the perspective of individuals with chronic pain. This mixed-method study included 49 former opioid users with chronic pain and used quantitative survey data and qualitative focus group data to identify themes pertaining to former opioid user's experience before, during, and after opioid cessation. Participants described several reasons for wanting to stop opioids including lack of efficacy, impact on quality of life, and concerns about addiction. Barriers to cessation included concerns about inadequate pain management and concerns about the impact of stopping opioids on mood. After opioid cessation, the sample was mixed regarding the benefit of cessation. Half of the former opioid users reported their pain to be better or the same after stopping opioids; however, 47% of the sample reported feeling worse pain since stopping their opioids. As the pendulum swings from pain control to drug control, we must ensure that the response to the opioid epidemic does not cause harm to individuals with chronic pain. Novel opioid cessation interventions are needed in combination with methods of addressing individual challenges and barriers to adequate pain relief including access to and provision of nonopioid alternatives for pain management.

Purpose: The relationship between exposure to abuse and interstitial cystitis/bladder pain syndrome (IC/BPS) is well-documented. However, studies have yet to examine posttraumatic stress disorder (PTSD), which develops following exposure to trauma and worsens health outcomes in chronic pain. We aimed to assess the prevalence and impact of PTSD in patients with IC/BPS, including their relation to genitourinary symptom presentation and widespread pain phenotype., Materials and Methods: We recruited 202 participants with chronic pain from an academic medical center and classified 64 individuals as IC/BPS based on validated epidemiological criteria. Participants completed self-reported questionnaires assessing trauma exposure, PTSD symptoms, emotional distress, pain, and urinary symptoms. Wilcoxon rank-sum tests assessed study aims comparing IC/BPS to other chronic pain., Results: Although elevated, IC/BPS trauma exposure rates were equivalent to that of other chronic pain conditions in the sample. Despite this equivalence, in comparison, IC/BPS patients had significantly higher rates of PTSD symptoms, with 42% meeting provisional diagnostic criteria for PTSD. Among IC/BPS, those meeting provisional criteria for PTSD had significantly higher incidence of lifetime sexual abuse, childhood trauma, and presentations consistent with the widespread pain phenotype. In IC/BPS, there was no association between PTSD and genitourinary symptoms, but provisional PTSD was associated with more pain, emotional distress, and poorer quality of life., Conclusions: We recommend that patients with IC/BPS and widespread pain have ongoing screening and monitoring of PTSD. We recommend using trauma-informed care practices with these patients to increase trust and safety, which could improve treatment compliance and follow-up., (© 2018 Wiley Periodicals, Inc.)

Chronic overlapping pain conditions (COPCs) are characterized by aberrant central nervous system processing of pain. This "centralized pain" phenotype has been described using a large and diverse set of symptom domains, including the spatial distribution of pain, pain intensity, fatigue, mood imbalances, cognitive dysfunction, altered somatic sensations, and hypersensitivity to external stimuli. Here, we used 3 cohorts, including patients with urologic chronic pelvic pain syndrome, a mixed pain cohort with other COPCs, and healthy individuals (total n = 1039) from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network to explore the factor structure of symptoms of centralized pain. Using exploratory and confirmatory factor analysis, we identified 2 general factors in all 3 cohorts, one characterized by a broad increased sensitivity to internal somatic sensations,environmental stimuli, and diffuse pain, termed Generalized Sensory Sensitivity, and one characterized by constitutional symptoms-Sleep, Pain, Affect, Cognition, Energy (SPACE). Longitudinal analyses in the urologic chronic pelvic pain syndrome cohort found the same 2-factor structure at month 6 and 1 year, suggesting that the 2-factor structure is reproducible over time. In secondary analyses, we found that Generalized Sensory Sensitivity particularly is associated with the presence of comorbid COPCs, whereas SPACE shows modest associations with measures of disability and urinary symptoms. These factors may represent an important and distinct continuum of symptoms that are indicative of the centralized pain phenotype at high levels. Future research of COPCs should accommodate the measurement of each factor.

Background: Adverse Childhood Experiences (ACEs) such as sexual and physical violence, serious illness, and bereavement have been linked to number of chronic pain conditions in adulthood, and specifically to urologic chronic pelvic pain syndrome (UCPPS)., Purpose: We sought to characterize the prevalence of ACEs in UCPPS using a large well-characterized cohort in comparison with a group of healthy controls. We also sought to determine the association of ACE severity with psychological factors known to impact pain and to determine whether ACEs are associated with patterns of improvement or worsening of symptom over a year of naturalistic observation., Methods: For longitudinal analyses we used functional clusters identifying broad classes of (a) improved, (b) worsened, and (c) stable groups for genitourinary pain and urinary symptoms. We employed a mediation/path analysis framework to determine whether ACEs influenced 1 year outcomes directly, or indirectly through worse perceptions of physical well-being., Results: ACE severity was elevated in UCPPS (n = 421) participants compared with healthy controls (n = 414; p < .001), and was most strongly associated with factors associated with complex chronic pain, including more diffuse pain, comorbid functional symptoms/syndromes, and worse perceived physical well-being (all p < .001). Finally, worse physical well-being mediated the relationship between ACE severity and less likelihood of painful symptom improvement (OR = .871, p = .007)) and a greater likelihood of painful symptom worsening (OR = 1.249, p = .003) at 1 year., Conclusions: These results confirm the association between ACEs and UCPPS symptoms, and suggest potential targets for therapeutic interventions in UCPPS., Clinical Trial Registration: NCT01098279.

Purpose: We examined health care seeking activities during a 12-month period in a cohort of men and women with urological chronic pelvic pain syndromes., Materials and Methods: A total of 191 men and 233 women with urological chronic pelvic pain syndrome were followed with biweekly, Internet based questionnaires about symptoms and health care seeking activities, including 1) health care provider contacts, 2) office visits, 3) emergency room/urgent care visits, 4) medication changes and 5) medical procedures. Multivariable modeling was used to determine the association of demographic and clinical variables with health care seeking. Super users were defined as individuals who reported health care seeking activity at least 11 times during the 23 biweekly assessments., Results: Health care seeking activities included a mean of 2.4 office contacts, 2.5 office visits, 1.9 medication changes, 0.9 medical procedures and 0.3 emergency room/urgent care visits. A total of 31 health care seeking super users accounted for 26% of health care seeking activities. Worse baseline pain severity and female gender were associated with a higher rate of all health care seeking activities except emergency room/urgent care visits. A nonurological chronic pain condition was associated with more provider contacts, office visits and medical procedures. Greater baseline depression symptoms were associated with more provider contacts, office visits and medication changes. Other examined variables, including patient age, symptom duration, catastrophizing, anxiety, urinary symptom severity and symptom variability, had a minimal association with health care seeking., Conclusions: Health care seeking activities were strongly influenced by the severity of pain in patients with urological chronic pelvic pain syndromes but not by urinary symptom severity. Women and patients with nonurological overlapping pain conditions were more likely to be seen and treated for symptoms., (Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We characterized the location and spatial distribution of whole body pain in patients with urological chronic pelvic pain syndrome using a body map. We also compared the severity of urinary symptoms, pelvic pain, nonpelvic pain and psychosocial health among patients with different pain patterns., Materials and Methods: A total of 233 women and 191 men with urological chronic pelvic pain syndrome enrolled in a multicenter, 1-year observational study completed a battery of baseline measures, including a body map describing the location of pain during the last week. Participants were categorized with pelvic pain if they reported pain in the abdomen and pelvis only. Participants who reported pain beyond the pelvis were further divided into 2 subgroups based on the number of broader body regions affected by pain, including an intermediate group with 1 or 2 additional regions outside the pelvis and a widespread pain group with 3 to 7 additional regions., Results: Of the 424 enrolled patients 25% reported pelvic pain only and 75% reported pain beyond the pelvis, of whom 38% reported widespread pain. Participants with a greater number of pain locations had greater nonpelvic pain severity (p <0.0001), sleep disturbance (p = 0.035), depression (p = 0.005), anxiety (p = 0.011), psychological stress (p = 0.005) and negative affect scores (p = 0.0004), and worse quality of life (p ≤0.021). No difference in pelvic pain and urinary symptom severity was observed according to increasing pain distribution., Conclusions: Three-quarters of the men and women with urological chronic pelvic pain syndrome reported pain outside the pelvis. Widespread pain was associated with greater severity of nonpelvic pain symptoms, poorer psychosocial health and worse quality of life but not with worse pelvic pain or urinary symptoms., (Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Although pain reduction is commonly the primary outcome in chronic pain clinical trials, physical functioning is also important. A challenge in designing chronic pain trials to determine efficacy and effectiveness of therapies is obtaining appropriate information about the impact of an intervention on physical function. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) and Outcome Measures in Rheumatology (OMERACT) convened a meeting to consider assessment of physical functioning and participation in research on chronic pain. The primary purpose of this article is to synthesize evidence on the scope of physical functioning to inform work on refining physical function outcome measurement. We address issues in assessing this broad construct and provide examples of frequently used measures of relevant concepts. Investigators can assess physical functioning using patient-reported outcome (PRO), performance-based, and objective measures of activity. This article aims to provide support for the use of these measures, covering broad aspects of functioning, including work participation, social participation, and caregiver burden, which researchers should consider when designing chronic pain clinical trials. Investigators should consider the inclusion of both PROs and performance-based measures as they provide different but also important complementary information. The development and use of reliable and valid PROs and performance-based measures of physical functioning may expedite development of treatments, and standardization of these measures has the potential to facilitate comparison across studies. We provide recommendations regarding important domains to stimulate research to develop tools that are more robust, address consistency and standardization, and engage patients early in tool development.

Unlabelled: There is increasing recognition that many if not most common chronic pain conditions are heterogeneous with a high degree of overlap or coprevalence of other common pain conditions along with influences from biopsychosocial factors. At present, very little attention is given to the high degree of overlap of many common pain conditions when recruiting for clinical trials. As such, many if not most patients enrolled into clinical studies are not representative of most chronic pain patients. The failure to account for the heterogeneous and overlapping nature of most common pain conditions may result in treatment responses of small effect size when these treatments are administered to patients with chronic overlapping pain conditions (COPCs) represented in the general population. In this brief review we describe the concept of COPCs and the putative mechanisms underlying COPCs. Finally, we present a series of recommendations that will advance our understanding of COPCs., Perspective: This brief review describes the concept of COPCs. A mechanism-based heuristic model is presented and current knowledge and evidence for COPCs are presented. Finally, a set of recommendations is provided to advance our understanding of COPCs., (Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.)

We developed the Michigan Body Map (MBM) as a self-report measure to assess body areas where chronic pain is experienced and to specifically quantify the degree of widespread body pain when assessing for centralized pain features (eg, fibromyalgia-like presentation). A total of 402 patients completed the measure in 5 distinct studies to support the validation of the original and a revised version of the MBM. Administration is rapid 39 to 44 seconds, and errors for the original MBM were detected in only 7.2% of the possible body areas. Most errors underestimated the number of painful areas or represented confusion in determining the right vs left side. The MBM was preferred (P = 0.013) and felt to better depict pain location (P = 0.001) when compared with the Widespread Pain Index checklist of the 2011 Fibromyalgia Survey Criteria, but participants did not express any preference between the MBM and Brief Pain Inventory body map. Based on the data from the first 3 studies, a revised version of the MBM was created including a front and back body image and improved guidance on right-sidedness vs left. The revised MBM was preferred when compared with the original and was more accurate in depicting painful body areas (P = 0.004). Furthermore, the revised MBM showed convergent and discriminant validity with other self-report measures of pain, mood, and function. In conclusion, the MBM demonstrated utility, reliability, and construct validity. This new measure can be used to accurately assess the distribution of pain or widespread bodily pain as an element of the fibromyalgia survey score.

Fibromyalgia (FM) is classified as a chronic pain condition accompanied by symptoms of fatigue, sleep problems, problems with cognition, negative mood, limited functional status, and the presence of other chronic overlapping pain conditions. Comprehensive assessment of all of these components can be challenging. This paper provides an overview of patient-reported approaches that can be taken to assess FM in the contexts of diagnosis, symptom monitoring, phenotyping/characterization, and for purposes of clinical trials., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to create symptom indexes, that is scores derived from questionnaires to accurately and efficiently measure symptoms of interstitial cystitis/bladder pain syndrome and chronic prostatitis/chronic pelvic pain syndrome, collectively referred to as urological chronic pelvic pain syndromes. We created these indexes empirically by investigating the structure of symptoms using exploratory factor analysis., Materials and Methods: As part of the MAPP (Multi-Disciplinary Approach to the Study of Chronic Pelvic Pain) Research Network 424 participants completed questionnaires, including GUPI (Genitourinary Pain Index), ICSI (Interstitial Cystitis Symptom Index) and ICPI (Interstitial Cystitis Problem Index). Individual items from questionnaires about bladder and pain symptoms were evaluated by principal component and exploratory factor analyses to identify indexes with fewer questions to comprehensively quantify symptom severity. Additional analyses included correlating symptom indexes with symptoms of depression, which is a known comorbidity of patients with pelvic pain., Results and Conclusions: Exploratory factor analyses suggested that the 2 factors pain severity and urinary severity provided the best psychometric description of items in GUPI, ICSI and ICPI. These factors were used to create 2 symptom indexes for pain and urinary symptoms. Pain, but not urinary symptoms, was associated with symptoms of depression on multiple regression analysis, suggesting that these symptoms may impact patients with urological chronic pelvic pain syndromes differently (B ± SE for pain severity = 0.24 ± 0.04, 95% CI 0.16-0.32, β = 0.32, p <0.001). Our results suggest that pain and urinary symptoms should be assessed separately rather than combined into 1 total score. Total scores that combine the separate factors of pain and urinary symptoms into 1 score may be limited for clinical and research purposes., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: We sought to determine the relationship among a history of physical or sexual abuse, pain experience, and depressive symptoms among women with chronic pelvic pain (CPP)., Study Design: This was a cross-sectional study of women who presented to a tertiary referral center for evaluation of CPP (N = 273). All participants completed standardized questionnaires to assess a history of physical or sexual abuse, pain severity, pain disability, and depressive symptoms. Subjects were grouped by abuse category and compared to CPP participants without history of abuse. Multinomial logistic regression models were used to determine the association between adolescent or adult and childhood physical or sexual abuse with pain intensity, pain-related disability, and depressive symptoms., Results: Logistic regression analyses indicated that, after controlling for age and education, none of the abuse categories was associated with pain severity. However, adolescent or adult sexual abuse predicted greater pain-related disability (odds ratio, 2.39; 95% confidence interval, 1.05-5.40), while both adolescent or adult physical and sexual abuse were associated with higher levels of depression (both P < .05). Level of education was significantly associated with pain intensity, pain disability, and depression., Conclusion: For our sample of women with CPP, a history of abuse during childhood or adulthood was not associated with differences in pain intensity, but adolescent or adult sexual abuse was associated with greater pain-related disability. A history of physical abuse or sexual abuse appears to hold a stronger relationship with current depressive symptoms than pain experience for women with CPP. Educational achievement holds a robust relationship with pain morbidity and depression for this population., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Purpose of Review: Much confusion has surrounded the purpose of the psychological assessment in the context of chronic pain. For many clinicians, the psychological assessment is used to rule out psychiatric illness and to identify the nonmedical causes for pain and disability. In essence, it is used to identify the causes of pain that fall outside of the biomedical model. Supported by over 30 years of evidence, the bio-psycho-social model acknowledges that psychosocial factors are inherent in chronic pain and require assessment if meaningful diagnostics and treatments are to occur., Recent Findings: Five broad categories of psychosocial assessment are relevant to chronic pain. These categories have been shown to enhance the diagnosis of the underlying forms of pain, predict the transition from acute to chronic status, and help to phenotype individuals for the discovery of the underlying mechanisms responsible for pain., Summary: Informed assessment of chronic pain needs to include relevant biological, psychological, and social domains. This article describes those domains and offers suggestions of specific instruments to use in clinical or research settings.

Unlabelled: The diversity of chronic pain syndromes and the methods employed to study them make integrating experimental findings challenging. This study performed coordinate-based meta-analyses using voxel-based morphometry imaging results to examine gray matter volume (GMV) differences between chronic pain patients and healthy controls. There were 12 clusters where GMV was decreased in patients compared with controls, including many regions thought to be part of the "pain matrix" of regions involved in pain perception, but also including many other regions that are not commonly regarded as pain-processing areas. The right hippocampus and parahippocampal gyrus were the only regions noted to have increased GMV in patients. Functional characterizations were implemented using the BrainMap database to determine which behavioral domains were significantly represented in these regions. The most common behavioral domains associated with these regions were cognitive, affective, and perceptual domains. Because many of these regions are not classically connected with pain and because there was such significance in functionality outside of perception, it is proposed that many of these regions are related to the constellation of comorbidities of chronic pain, such as fatigue and cognitive and emotional impairments. Further research into the mechanisms of GMV changes could provide a perspective on these findings., Perspective: Quantitative meta-analyses revealed structural differences between brains of individuals with chronic pain and healthy controls. These differences may be related to comorbidities of chronic pain., (Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.)

The Internet is rapidly becoming a part of the pain practitioner's arsenal for bringing relief to patients. Along with the promise come a number of caveats for selecting the most appropriate technologies for a given practice. This article provides an overview of why the Internet holds potential for filling a gap in pain practice, reviews some of the fastest emerging uses of the Internet for pain, and identifies both merits and limitations the practitioner should consider when contemplating adopting an Internet technology for his or her practice.

Unlabelled: The primary symptom of fibromyalgia (FM) is chronic, widespread pain; however, patients report additional symptoms including decreased concentration and memory. Performance-based deficits are seen mainly in tests of working memory and executive function. Neural correlates of executive function were investigated in 18 FM patients and 14 age-matched healthy controls during a simple Go/No-Go task (response inhibition) while they underwent functional magnetic resonance imaging (fMRI). Performance was not different between FM and healthy control, in either reaction time or accuracy. However, fMRI revealed that FM patients had lower activation in the right premotor cortex, supplementary motor area, midcingulate cortex, putamen and, after controlling for anxiety, in the right insular cortex and right inferior frontal gyrus. A hyperactivation in FM patients was seen in the right inferior temporal gyrus/fusiform gyrus. Despite the same reaction times and accuracy, FM patients show less brain activation in cortical structures in the inhibition network (specifically in areas involved in response selection/motor preparation) and the attention network along with increased activation in brain areas not normally part of the inhibition network. We hypothesize that response inhibition and pain perception may rely on partially overlapping networks, and that in chronic pain patients, resources taken up by pain processing may not be available for executive functioning tasks such as response inhibition. Compensatory cortical plasticity may be required to achieve performance on a par with control groups., Perspective: Neural activation (fMRI) during response inhibition was measured in fibromyalgia patients and controls. FM patients show lower activation in the inhibition and attention networks and increased activation in other areas. Inhibition and pain perception may use overlapping networks: resources taken up by pain processing may be unavailable for other processes., (Copyright © 2011 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Context: Research consistently has evidenced the reliability and validity of the Pain Beliefs and Perceptions Inventory (PBPI). The instrument, however, has not been tested for its applicability and validity in non-Western populations., Objectives: To translate the English language version of the PBPI into Chinese (ChPBPI) and to evaluate its reliability, validity, and factor structure., Methods: A total of 208 Chinese patients with mixed origin chronic pain were recruited from an orthopedic specialist outpatient clinic associated with a public hospital in Hong Kong. In addition to the ChPBPI, patients were administered the Chronic Pain Grade (CPG) questionnaire, the Pain Catastrophizing Scale (PCS), the Center for Epidemiological Studies-Depression Scale (CES-D), and questions assessing sociodemographic characteristics., Results: Using the original factor structure of the PBPI as a model, confirmatory factor analyses revealed that all four ChPBPI scales demonstrated good data-model fit (CFI≥0.92) and adequate internal consistency (Cronbach's αs: 0.60-0.76). The four ChPBPI scales showed significant positive correlations with CES-D, PCS, pain intensity, and disability. Results of hierarchical multiple regression analyses showed that the ChPBPI scales predicted concurrent depression (F(4, 187)=6.01, P<0.001), pain intensity (F(4, 186)=4.61, P<0.01), and pain disability (F(4, 190)=3.54, P<0.05) scores., Conclusion: These findings support the factorial validity of the scales of the ChPBPI, and its reliability and construct validity. Now clinically relevant beliefs about pain can be assessed among Chinese patients with chronic pain., (Copyright © 2011 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.)

Individuals with chronic widespread pain, including those with fibromyalgia, pose a particular challenge to treatment, given the modest effectiveness of pharmacological agents for this condition. The growing consensus indicates that the best approach to treatment involves the combination of pharmacological and non-pharmacological interventions. Several non-pharmacological interventions, particularly exercise and cognitive-behavioural therapy (CBT), have garnered good evidence of effectiveness as stand-alone, adjunctive treatments for patients with chronic pain. In this article, evidenced-based, non-pharmacological management techniques for chronic widespread pain are described by using two broad categories, exercise and CBT. The evidence for decreasing pain, improving functioning and changing secondary symptoms is highlighted. Lastly, the methods by which exercise and CBT can be combined for a multi-component approach, which is consistent with the current evidence-based guidelines of several American and European medical societies, are addressed., (Copyright © 2011 Elsevier Ltd. All rights reserved.)