Presence of endometriosis and chronic overlapping pain conditions negatively impacts the pain experience in women with chronic pelvic-abdominal pain: A cross-sectional survey.

BACKGROUND: Evidence of overlap between endometriosis and chronic pain conditions is emerging; however, little is known about how the pain experience differs based on the presence or absence of endometriosis. OBJECTIVES: In a sample of women reporting chronic pelvic-abdominal pain (CPP), the aim of this study was to characterize differences in pain symptomatology between women with and without endometriosis and to examine the influence of chronic overlapping pain conditions (COPCs) on pain among these two groups. DESIGN: This was a cross-sectional study, based on an online survey. METHODS: Participants (aged 18+ years) completed a survey collecting pain diagnoses and symptoms assessing pelvic pain severity, pain interference, and pain impact. Independent sample t-tests, chi-square, and multiple linear regression models were employed to analyze group differences in pain symptomatology and COPCs. RESULTS: Of the 525 respondents with CPP, 25% (n = 133) reported having endometriosis. Women with endometriosis were younger at the onset of pelvic pain, relative to women without endometriosis (p = 0.04). There were no differences in age, race, ethnicity, or duration of pelvic pain between women with and without endometriosis. Women with endometriosis reported higher pelvic pain severity (+0.8, 95% CI = 0.4-1.1), pain interference (+5.9, 95% CI = 2.4-9.3), and pain impact (+1.9, 95% CI = 0.8-2.9). Endometriosis was associated with a higher number of COPCs (p = 0.003), with 25% (n = 33) of women reporting ⩾3 overlapping pain conditions compared with 12% (n = 45) of those without endometriosis. Women with endometriosis had a higher frequency of fibromyalgia (p < 0.001), chronic fatigue syndrome (p < 0.001), and temporomandibular disorder (p = 0.001). The number of COPCs was associated with higher pain severity, interference, and impact, independently of endometriosis. CONCLUSION: Women with endometriosis experienced higher levels of pain-related burden and COPCs compared with those without endometriosis. Pain intensity, interference, and impact increased with a higher number of pain conditions regardless of endometriosis presence.

Presence of endometriosis and chronic overlapping pain conditions negatively impacts the pain experience in women with chronic pelvic­abdominal pain: A cross-sectional surveyThe presence of endometriosis was associated with a higher number of chronic overlapping pain conditions (COPCs) and greater pain symptomatology, while a greater number of COPCs corresponded to increased pain burden among women with and without endometriosis. These findings underscore the need for a more comprehensive assessment of endometriosis that addresses the full experience of the disease, including its comorbidities. A greater characterization and measurement of COPCs has the potential to facilitate the development of tailored interventions for individuals with pain comorbidities, thereby contributing to improved clinical care strategies for endometriosis-related pain.

The Chronic Overlapping Pain Condition Screener.

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.

Case report: Remission of chronic low back pain and oral dysesthesia comorbid with attention deficit/hyperactivity disorder by treatment with atomoxetine and pramipexole.

Introduction: Oral dysesthesia is a disease characterized by pain and/or abnormal sensations in the oral region, without any organic abnormality. Its symptoms include pain, and it is considered to be a disorder associated with idiopathic oral-facial pain. It is also known that idiopathic oral-facial pain tends to coexist with chronic musculoskeletal pain, including low back pain, even before its onset. Such coexisting idiopathic pain conditions are also called chronic overlapping pain conditions (COPCs). In general, COPCs are often refractory to treatment. Recently, it has been reported that attention deficit hyperactivity disorder (ADHD) is associated with many COPCs, such as pain in the facial and lower back regions and so on. However, there are no reports of (1) ADHD as a comorbidity with oral dysesthesia (OD) or (2) of the therapeutic effects of ADHD medications or dopamine agonists on low back pain and OD or an (3) evaluation of cerebral blood flow over time after treatment with these medications for OD and low back pain. Case Presentation: In this study, we report the case of an 80-year-old man with OD and chronic low back pain that persisted for more than 25 years. His OD and chronic back pain were refractory to standard treatment, prevented him from continuing work, and tended to be exacerbated by conflicts in his relationship with his son. In recent years, ADHD has often been found to be comorbid with chronic pain, and ADHD medications have been reported to improve chronic pain as well. The patient was confirmed to have undiagnosed ADHD and was treated with the ADHD medication atomoxetine and dopamine agonist pramipexole, which dramatically improved his OD, chronic back pain, and cognitive function. Furthermore, along the course of treatment, there was improvement in cerebral blood flow in his prefrontal cortex, which was thought to reflect improved function in the region. Consequently, he was able to resume work and improve his family relationships. Conclusion: Therefore, in the cases of ODs and COPCs, screening for ADHD and, if ADHD is diagnosed, ADHD medications or dopamine agonists may be considered.

Pathogenesis and Differential Diagnosis of Temporomandibular Joint Disorders.

Temporomandibular disorders (TMDs) are an umbrella term including disorders of the temporomandibular joint and muscles of the masticatory system. They are the most common nonodontogenic cause of pain in the orofacial region. A clear understanding of various conditions, underlying mechanisms, clinical presentation, and examination skills is required to effectively diagnose and manage these patients.

Polygenic Contributions to Chronic Overlapping Pain Conditions in a Large Electronic Health Record Sample.

Chronic overlapping pain conditions (COPCs) are believed to share common etiological mechanisms involving central sensitization. Genetic and environmental factors putatively combine to influence susceptibility to central sensitization and COPCs. This study employed a genome-wide polygenic risk score approach to evaluate genetic influences on 8 common COPCs. COPCs were identified by International Classification of Disease codes in Vanderbilt's deidentified clinical biorepository (BioVU), with each COPC condition empirically weighted for the level of central sensitization based on prior work. A centralized pain score (CPS) was calculated for 55,340 individuals by summing the weighted number of COPCs. Overall, 12,502 individuals (22.6%) were diagnosed with at least 1 COPC, with females exhibiting nearly twice the mean CPS as males. To assess the genetic influence on centralized pain in COPCs, 6 pain polygenic risk scores (PRSs) were developed using UK Biobank data to predict 6 pain criteria (no pain, neck/shoulder, abdomen, hip, knee, low back pain). These PRSs were then deployed in the BioVU cohort to test for association with CPS. In regression models adjusted for age, sex, and BMI, all pain PRSs except hip pain were significantly associated with CPS. Our findings support a shared polygenic influence across COPCs potentially involving central sensitization mechanisms. PERSPECTIVE: This study used a polygenic risk score approach to investigate genetic influences on chronic overlapping pain conditions. Significant findings in this study provide evidence supporting previous hypotheses that a shared polygenic influence involving central sensitization may underly chronic overlapping pain conditions and can guide future biomarker and risk assessment research.

Circulating Polyunsaturated Fatty Acids and Pain Intensity in Five Chronic Pain Conditions.

Pain intensity is well-known to be influenced by a wide range of biobehavioral variables. Nutritional factors, however, have not been generally considered for their potential importance. This cross-sectional study examined associations between erythrocyte omega-6 (n-6) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and pain intensity in 605 adults. Pain intensity was computed on a 0 to 100 numeric rating scale from questions about 5 chronic pain conditions: orofacial pain, headache, low back pain, irritable bowel syndrome, and bodily pain. For each pain condition, multiple linear regression tested the hypothesis that a higher ratio of n-6 arachidonic acid to the sum of n-3 eicosapentaenoic acid and docosahexaenoic acid (AA/(EPA+DHA) was associated with greater pain intensity. In covariate-adjusted analysis, orofacial pain intensity increased 5.7 points (95% CI: 1.4, 9.9) per unit increase in n-6/n-3 PUFA ratio. Likewise, a 1 unit increase in n-6/n-3 PUFA ratio was associated with significant increases in pain intensity (range 5-8 points) of headache pain, low back pain, and bodily pain, but not abdominal pain. Separate multiple linear regression models investigated the independent strength of association of individual PUFAs to the intensity of each pain condition. Overall, n-3 docosahexaenoic acid was most strongly, and inversely, associated with pain intensity. PERSPECTIVE: A higher ratio of n-6/n-3 long-chain polyunsaturated fatty acids was associated greater pain intensity for orofacial pain, headache, low back pain, and bodily pain, but not abdominal pain. The n-6/n-3 PUFA ratio was more consistently associated with pain intensity than any individual constituent of the long-chain PUFA ratio.

Migraine in the context of chronic primary pain, chronic overlapping pain disorders, and functional somatic disorders: A narrative review.

OBJECTIVE: To contextualize migraine as the most common primary headache disorder in relation to other chronic primary pain and non-pain functional somatic and mental conditions. BACKGROUND: Migraine is increasingly understood as a sensory processing disorder within a broader spectrum of symptom disorders. This has implications for diagnosis and treatment. METHOD: Narrative review based on a search of the literature of the last 15 years on the overlap of migraine with other symptom disorders. RESULTS: Migraine as the prototypical primary headache disorder not only comprises many non-headache symptoms in itself, it also shows high comorbidity with other chronic pain and non-pain conditions (e.g., fibromyalgia syndrome, irritable bowel syndrome, functional non-epileptic seizures, depression, anxiety, and posttraumatic stress disorder). Such "symptom disorders" share several etiological factors (e.g., female preponderance, psychological vulnerability) and psychophysiological mechanisms (e.g., altered sensory processing, pain expectancy). These facts are acknowledged by several recent integrative conceptualizations such as chronic primary pain, chronic overlapping pain conditions, or functional somatic disorders. Accordingly, migraine management increasingly addresses the total symptom burden and individual contributors to symptom experience, and thus incorporates centrally acting pharmacological and non-pharmacological, that is, psychological and behavioral, treatment approaches. CONCLUSIONS: Migraine and also other primary headache disorders should be seen as particular phenotypes within a broader spectrum of symptom perception and processing disorders that require integrative diagnostics and treatment. A harmonization of classifications and better interdisciplinary collaboration are desirable.

Rationale and design of a multicenter randomized clinical trial of vestibulodynia: understanding pathophysiology and determining appropriate treatments (vestibulodynia: UPDATe).

BACKGROUND: Limited data are available to establish evidence-based management protocols for vestibulodynia (VBD), a chronic vulvar pain condition that affects approximately 14 million women in the U.S. For the purposes of the study, our group subdivided VBD subtypes that may benefit from different types of treatment: 1) VBD peripheral (VBD-p), characterized by pain localized to the vulvar vestibule and 2) VBD central (VBD-c), characterized by VBD alongside one or more other chronic overlapping pain conditions (e.g. irritable bowel syndrome, temporomandibular disorder, and fibromyalgia syndrome) that affect remote body regions. Here, we describe the rationale and design of an NIH-funded multicenter clinical trial comparing the effectiveness of topical and/or systemic medication for alleviating pain and normalizing pain- relevant biomarkers among women with VBD-p and VBD-c. METHODS: Participants will be randomly assigned to one of four parallel arms: peripheral treatment with 5% lidocaine + 0.5 mg/ml 0.02% oestradiol compound cream + oral placebo pill, 2) central treatment with the tricyclic antidepressant nortriptyline + placebo cream, 3) combined peripheral cream and central pill treatments, or 4) placebo cream and placebo pill. The treatment phase will last 16 weeks, with outcome measures and biomarkers assessed at 4 time points (0, 8, 16, and 24 weeks). First, we will compare the efficacy of treatments in alleviating pain using standardized tampon insertion with a numeric rating scale and self-reported pain on the short form McGill Pain Questionnaire. Next, we will compare the efficacy of treatments in improving perceived physical, mental, and sexual health using standardized questionnaires. Finally, we will measure cytokines and microRNAs in local vaginal and circulating blood samples using multiplex assays and RNA sequencing, and determine the ability of these biomarkers to predict treatment response. CONCLUSION: This is the first multicenter randomized controlled trial to evaluate the efficacy of peripherally and centrally acting medications currently used in clinical practice for treating unique VBD subtypes based on distinct clinical and biological signatures. ADMINISTRATIVE INFORMATION: Vestibulodynia UPDATe is a multi-centre, two-by-two factorial designed randomized, double-blind, placebo-controlled trial registered at clinical trials.gov (NCT03844412). This work is supported by the R01 HD096331 awarded to Drs. Nackley, Rapkin, Geller and Carey by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD).Key messagesPeripheral lidocaine and oestradiol and centrally-targeted nortriptyline medications are used for the treatment of pain in women with VBD, but there is a lack of data from well-powered RCTs.This two-by-two factorial RCT will test the efficacy of these medications in VBD subtypes characterized by distinct clinical characteristics and biomarker profiles.We hope that results will provide clinicians with scientific evidence of therapeutic efficacy in distinct VBD subtypes in an effort to direct and optimize treatment approaches.

Validation of ICD-9 Codes for Identification of Chronic Overlapping Pain Conditions.

Chronic overlapping pain conditions (COPCs) are a collection of chronic pain syndromes that often co-occur and are thought to share underlying nociplastic pathophysiology. Since they can manifest as seemingly unrelated syndromes they have historically been studied in isolation. Use of International Classification of Diseases (ICD) codes in medical records has been proposed as a means to identify and study trends in COPCs at the population level, however validated code sets are needed. Recently, a code set comprising ICD-10 codes as proxies for 11 COPCs was validated. The goal of this project was to validate a code set composed of ICD-9 codes for the identification of COPCs in administrative datasets. Data was extracted using the Electronic Medical Record Search Engine at the University of Michigan Health System from January 1st, 2011 to January 1st, 2015. The source population were patients with one of the candidate ICD-9 codes corresponding to various COPCs. Natural language searches were used as a reference standard. If code sets met a pre-specified threshold of agreement between ICD-9 codes and natural language searches (≥ 70%), they were retained and diagnostic accuracy statistics were calculated for each code set. Validated ICD-9 code sets were generated for 10 of the 11 COPCs evaluated. The majority had high levels of diagnostic accuracy, with all but one code set achieving ≥ 80% specificity, sensitivity, and predictive values. This code set may be used by pain researchers to identify COPCs using ICD-9 codes in administrative datasets.

COPCs share underlying nociplastic etiology; it is important to distinguish these from other pain etiologies to better understand their prevalence, identify comorbid conditions, and understand trends in their pharmacologic management.COPCs have historically been under-recognized and -studied due to challenges with identifying them in administrative datasets.A validated code set for identifying COPCs in administrative datasets using ICD-10 codes exists, however this limits any longitudinal studies as ICD-10 coding was not fully implemented until 2015.This study used natural language searches to validate a set of ICD-9 codes for identifying COPCs.Code sets were able to be validated for 10 of 11 COPCs with high specificity, sensitivity, and predictive values.

Circulating polyunsaturated fatty acids, pressure pain thresholds, and nociplastic pain conditions.

OBJECTIVE: Polyunsaturated fatty acids (PUFAs) play a role in pain regulation. This study sought to determine whether free PUFAs found in red blood cells also play a role in nociceptive processing. We examined associations between circulating PUFAs and nociceptive thresholds to noxious mechanical stimuli. We also determined whether nociceptive thresholds were associated with nociplastic pain conditions. METHODS: This cross-sectional study used stored red bloods cells and data from 605 adult participants in the OPPERA-2 study of chronic overlapping pain conditions. In OPPERA-2 adults completed quantitative sensory testing in which pressure algometry measured deep muscular tissue sensitivity at six anatomical sites. Standardized protocols classified adults for presence or absence of five nociplastic pain conditions: temporomandibular disorder, headache, low back pain, irritable bowel syndrome and fibromyalgia. Liquid chromatography tandem mass spectroscopy quantified erythrocyte PUFAs. We conducted three sets of analyses. First, a multivariable linear regression model assessed the association between n-6/n-3 PUFA ratio and the number of overlapping nociplastic pain conditions. Second, a series of 36 multivariable linear regression models assessed covariate-adjusted associations between PUFAs and nociceptive thresholds at each of six anatomical sites. Third, a series of 30 multivariable linear regression models assessed covariate-adjusted associations between nociceptive thresholds at six anatomical sites and each of five pain conditions. RESULTS: In multiple linear regression, each unit increase in n-6/n-3 PUFA ratio was associated with more pain conditions (ß = 0.30, 95% confidence limits: 0.07, 0.53, p = 0.012). Omega-6 linoleic acid and arachidonic acid were negatively associated with lower nociceptive thresholds at three and at five, respectively, anatomical sites. In contrast, omega-3 alpha-linolenic acid, eicosapentaenoic acid, docosahexaenoic acid and the n-6/n-3 PUFA ratio were not associated with nociceptive thresholds at any site. Pain cases had significantly lower nociceptive thresholds than non-case controls at all anatomical sites. CONCLUSION: A higher n-6/n-3 PUFA ratio was associated with more pain conditions. Omega-6 PUFAs may promote a generalized upregulation of nociceptive processing.

Early and Late Transcriptional Changes in Blood, Neural, and Colon Tissues in Rat Models of Stress-Induced and Comorbid Pain Hypersensitivity Reveal Regulatory Roles in Neurological Disease.

Background: Irritable bowel syndrome (IBS) and temporomandibular disorder (TMD) are two chronic pain conditions that frequently overlap in the same individual, more commonly in women. Stress is a significant risk factor, exacerbating or triggering one or both conditions. However, the mechanisms underlying IBS-TMD co-morbidity are mostly unknown. Aim: To detect both specific and common stress-induced visceral hypersensitivity (SIH) and comorbid TMD-IBS pain hypersensitivity (CPH) genetic signatures over time. Method: Twenty-four female rats were randomly assigned to one of three experimental groups: naïve, SIH, and CPH (orofacial pain plus stress). RNA was extracted from blood, colon, spinal cord, and dorsal root ganglion 1 or 7 weeks after the stress paradigm. We combined differential gene expression and co-expression network analyses to define both SIH and CPH expression profiles across tissues and time. Results: The transcriptomic profile in blood and colon showed increased expression of genes enriched in inflammatory and neurological biological processes in CPH compared to SIH rats, both at 1 and 7 weeks after stress. In lumbosacral spinal tissue, both SIH and CPH rats compared to naïve revealed decreased expression of genes related to synaptic activity and increased expression of genes enriched in "angiogenesis," "Neurotrophin," and "PI3K-Akt" pathways. Compared to SIH, CPH rats showed increased expression of angiogenesis-related genes 1 week after exposure to stress, while 7 weeks post-stress the expression of these genes was higher in SIH rats. In dorsal root ganglia (DRG), CPH rats showed decreased expression of immune response genes at week 1 and inhibition of nerve myelination genes at 7 weeks compared to naïve. For all tissues, we observed higher expression of genes involved in ATP production in SIH compared to CPH at 1 week and this was reversed 7 weeks after the induction of stress. Conclusion: Our study highlights an increased inflammatory response in CPH compared to SIH rats in the blood and colon. DRG and spinal transcriptomic profiles of both CPH and SIH rats showed inhibition of synaptic activity along with activation of angiogenesis. Targeting these biological processes may lead to a more profound understanding of the mechanisms underlying IBS-TMD comorbidities and new diagnostic and therapeutic strategies.

Whole Body Pain Distribution and Risk Factors for Widespread Pain Among Patients Presenting with Abdominal Pain: A Retrospective Cohort Study.

INTRODUCTION: Abdominal pain frequently co-occurs with pain in other body sites. Chronic overlapping pain conditions (COPCs) represent a group of widespread pain diagnoses. Our study characterized how patterns of somatic pain distribution are associated with COPCs and aimed to characterize predictors of widespread pain among patients with chronic abdominal pain. METHODS: This retrospective cohort study included adults presenting to a tertiary pain clinic, reporting abdominal pain at their initial visit, and with a follow-up visit at 12 months. Body maps divided patients into localized, intermediate, and widespread pain distribution patterns. Diagnostic and psychosocial measures were assessed across groups at the initial and follow-up visits. We analyzed the association of baseline diagnoses and demographics and time-varying changes in psychosocial measures from initial to follow-up visit with changes in pain distribution over time with alternating logistic regression (ALR). RESULTS: Among 258 patients, most were female (91.5%) and reported widespread pain (61.5%). Those with widespread pain at baseline reported elevated anger and 60.0% of patients remained in the same pain category at follow-up. Multivariable ALR demonstrated higher pain interference (AOR 1.06, 95% CI 1.02-1.10, P = 0.002), higher anxiety (AOR 1.05, 95% CI 1.01-1.09, P = 0.01), more than one COPC at initial visit (AOR 2.85, 95% CI 1.59-5.11, P = 0.0005), and initial visit widespread pain categorization (AOR 4.18, 95% CI 2.20-8.00, P < 0.0001) were associated with an increased risk of widespread pain at the follow-up visit. CONCLUSION: Most patients with abdominal pain report additional pain locations at multiple other body sites, and non-localized pain persists 12 months after pain treatment. Screening for widespread pain and COPC at the initial visit may identify patients at higher risk for persistent or new-onset widespread pain, and interventions to reduce pain interference and anxiety may promote reversal of widespread pain.

Genome-wide analysis identifies impaired axonogenesis in chronic overlapping pain conditions.

Chronic pain is often present at more than one anatomical location, leading to chronic overlapping pain conditions. Whether chronic overlapping pain conditions represent a distinct pathophysiology from the occurrence of pain at only one site is unknown. Using genome-wide approaches, we compared genetic determinants of chronic single-site versus multisite pain in the UK Biobank. We found that different genetic signals underlie chronic single-site and multisite pain with much stronger genetic contributions for the latter. Among 23 loci associated with multisite pain, nine loci replicated in the HUNT cohort, with the DCC netrin 1 receptor (DCC) as the top gene. Functional genomics identified axonogenesis in brain tissues as the major contributing pathway to chronic multisite pain. Finally, multimodal structural brain imaging analysis showed that DCC is most strongly expressed in subcortical limbic regions and is associated with alterations in the uncinate fasciculus microstructure, suggesting that DCC-dependent axonogenesis may contribute to chronic overlapping pain conditions via corticolimbic circuits.

Electronic Delivery of Pain Education for Chronic Overlapping Pain Conditions: A Prospective Cohort Study.

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.

[Endometriosis and chronic overlapping pain conditions]. / Endometriose und chronische überlappende Schmerzsyndrome.

BACKGROUND: The concept of chronic overlapping pain conditions (COPC) is relatively unknown in German pain medicine. AIMS: Definition, prevalence, shared etiological and pathophysiological mechanisms of COPC. Summary of recommendations of the interdisciplinary S2k guidelines on diagnostics and treatment of endometriosis relevant for pain physicians. METHODS: Selective search of literature in PubMed and selection of recommendations of the S2k guidelines on diagnostics and treatment of endometriosis. RESULTS: According to the US National Institutes of Health, COPCs comprise chronic fatigue syndrome, chronic (unspecific) low back pain, chronic tension headache, endometriosis, fibromyalgia syndrome, migraine, painful bladder syndrome, temporomandibular disorder and vulvodynia. Shared etiological factors are family aggregation, childhood adversities and major or traumatic life events. A major shared pathophysiological mechanism is altered processing of stimuli in the central nervous system. Patients with endometriosis should be screened for other chronic pain conditions and psychological distress. The physical examination should check for local (myofascial trigger points) and generalized signs of hyperalgesia and allodynia indicating central sensitization. In cases of endometriosis with COPCs repeated surgery for pain relief should be avoided. Amitriptyline and duloxetine can be considered as pharmacological treatment options. DISCUSSION: Pain physicians can play a role in the management of patients with endometriosis and COPCs. A multimodal therapy should include physiotherapy and pain-related psychological treatment and possibly centrally acting pain modulation medication.

Examining the Adjustment Patterns of Adults With Multiple Chronic Pain Conditions and Multiple Pain Sites: More Pain, No Gain.

The present study examined how multiple chronic pain conditions and pain sites are associated with sociodemographics, chronic pain adjustment profiles, and emotional distress. A total of 2,407 individuals who reported at least 6 months of having consistent pain severity, pain interference, and/or emotional burden due to pain were recruited through random digit dialing across the United States. Participants' chronic pain adjustment profiles (ie, pain intensity, pain interference, emotional burden, pain catastrophizing, pain coping, pain attitudes, and social resources) were assessed. Anxiety and depressive symptoms were also measured using a subsample of 181 participants who provided 3-month follow-up data. More than 60% of individuals with chronic pain reported having multiple pain conditions. Middle-aged single women with fibromyalgia, disability and of low socioeconomic status reported a greater number of pain conditions and pain sites. Structural equation modeling revealed that a higher number of pain conditions and sites were associated with more dysfunctional chronic pain adjustment profiles. The subsample analyses showed that reporting a greater number of pain conditions predicted a higher level of depression and anxiety 3 months later, controlling for pain-related anxiety and depressive symptoms, pain severity and interference at baseline. Having multiple pain conditions and sites may represent a psychosocial barrier to successful adjustment to chronic pain. PERSPECTIVE: This article argues for the importance of assessing the number of co-occurring chronic pain conditions and bodily areas that are affected by pain in both pain research and clinical settings. Measuring and incorporating such information could potentially enhance our nascent understanding of the adjustment processes of chronic pain.

ICD-10 Codes for the Study of Chronic Overlapping Pain Conditions in Administrative Databases.

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.

Brain glial activation in fibromyalgia - A multi-site positron emission tomography investigation.

Fibromyalgia (FM) is a poorly understood chronic condition characterized by widespread musculoskeletal pain, fatigue, and cognitive difficulties. While mounting evidence suggests a role for neuroinflammation, no study has directly provided evidence of brain glial activation in FM. In this study, we conducted a Positron Emission Tomography (PET) study using [11C]PBR28, which binds to the translocator protein (TSPO), a protein upregulated in activated microglia and astrocytes. To enhance statistical power and generalizability, we combined datasets collected independently at two separate institutions (Massachusetts General Hospital [MGH] and Karolinska Institutet [KI]). In an attempt to disentangle the contributions of different glial cell types to FM, a smaller sample was scanned at KI with [11C]-L-deprenyl-D2 PET, thought to primarily reflect astrocytic (but not microglial) signal. Thirty-one FM patients and 27 healthy controls (HC) were examined using [11C]PBR28 PET. 11 FM patients and 11 HC were scanned using [11C]-L-deprenyl-D2 PET. Standardized uptake values normalized by occipital cortex signal (SUVR) and distribution volume (VT) were computed from the [11C]PBR28 data. [11C]-L-deprenyl-D2 was quantified using λ k3. PET imaging metrics were compared across groups, and when differing across groups, against clinical variables. Compared to HC, FM patients demonstrated widespread cortical elevations, and no decreases, in [11C]PBR28 VT and SUVR, most pronounced in the medial and lateral walls of the frontal and parietal lobes. No regions showed significant group differences in [11C]-L-deprenyl-D2 signal, including those demonstrating elevated [11C]PBR28 signal in patients (p's ≥ 0.53, uncorrected). The elevations in [11C]PBR28 VT and SUVR were correlated both spatially (i.e., were observed in overlapping regions) and, in several areas, also in terms of magnitude. In exploratory, uncorrected analyses, higher subjective ratings of fatigue in FM patients were associated with higher [11C]PBR28 SUVR in the anterior and posterior middle cingulate cortices (p's < 0.03). SUVR was not significantly associated with any other clinical variable. Our work provides the first in vivo evidence supporting a role for glial activation in FM pathophysiology. Given that the elevations in [11C]PBR28 signal were not also accompanied by increased [11C]-L-deprenyl-D2 signal, our data suggests that microglia, but not astrocytes, may be driving the TSPO elevation in these regions. Although [11C]-L-deprenyl-D2 signal was not found to be increased in FM patients, larger studies are needed to further assess the role of possible astrocytic contributions in FM. Overall, our data support glial modulation as a potential therapeutic strategy for FM.

Phenotypic Features of Central Sensitization.

PURPOSE: The current manuscript reviews approaches for phenotyping central sensitization (CS). METHODS: The manuscript covers the concept of diagnostic phenotyping, use of endophenotypes, biomarkers, and symptom clusters. Specifically, the components of CS that include general sensory sensitivity (assessed by quantitative sensory testing) and a symptom cluster denoting sleep difficulties, pain, affect, cognitive difficulties, and low energy (S.P.A.C.E.). RESULTS: Each of the assessment domains are described with reference to CS and their presence in chronic overlapping pain conditions (COPCs) - conditions likely influenced by CS. CONCLUSIONS: COPCs likely represent clinical diagnostic phenotypes of CS. Components of CS can also be assessed using QST or self-report instruments designed to assess single elements of CS or more general composite indices.

How can precision medicine be applied to temporomandibular disorders and its comorbidities?

The Eighth Scientific Meeting of The TMJ Association, Ltd. was held in Bethesda, Maryland, September 11-13, 2016. As in the past, the meeting was cosponsored by components of the National Institutes of Health with speakers invited to review the state of temporomandibular disorder science and propose recommendations to further progress. The theme of precision medicine, which aims to tailor disease treatment and prevention to match the characteristics of an individual patient (genetic, epigenetic, environmental, lifestyle) underscored the current consensus that temporomandibular disorders are no longer viewed as local conditions of jaw pain and dysfunction. Rather, they represent a complex family of biopsychosocial disorders that can progress to chronic pain, most often accompanied by one or more other chronic pain conditions. Temporomandibular disorders and these comorbidities, called chronic overlapping pain conditions, predominantly or exclusively affect women in their childbearing years and reflect central nervous system sensitization. Presenters at the meeting included leaders in temporomandibular disorder and pain research, temporomandibular disorder patients and advocates, and experts in other fields or in the use of technologies that could facilitate the development of precision medicine approaches in temporomandibular disorders.