Comorbid Pain Research Articles

Initial validation of the expectancies for Benzodiazepine Analgesia Scale.

Chronic pain populations exhibit greater prevalence of benzodiazepine (BZD) prescription (vs. the general population) and greater likelihood of BZD use not as prescribed and dependence symptoms. Individuals report taking BZDs for pain relief, potentially contributing to maintenance/escalation of BZD use and hazardous couse with prescription opioids. Identifying cognitive factors underlying pain-BZD use relations represents a critical step toward understanding the role of pain in BZD use trajectories. Outcome expectancies for substance-related analgesia have been implicated in pain-substance use comorbidity (e.g., alcohol), and there is reason to believe these processes may extend to BZD use. The present study aimed to examine psychometric properties of a newly adapted Expectancies for Benzodiazepine Analgesia (EBA) scale and probe associations between EBA scores and prescription opioid use behaviors. Participants were 306 adults (38.9% females) endorsing chronic pain and current BZD prescription who completed an online survey. Results provided initial support for psychometric validity of the EBA: evidence of single-factor structure with good model fit (Bollen-Stine bootstrap p = .101), excellent internal consistency (α = .93), and evidence of concurrent validity via correlations with pain variables, likelihood of BZD use not as prescribed, BZD dependence symptoms, and self-reported BZD use for pain relief. Exploratory findings among participants prescribed opioids indicated positive covariation between EBA scores and behaviors associated with higher risk opioid use. This is, to our knowledge, the first study to assess analgesia expectancies for BZD use. BZD analgesic expectancies warrant further study as a treatment target in comorbid pain and BZD use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Global trends and hotspots in pain associated with bipolar disorder in the last 20 years: a bibliometric analysis

PurposeThe prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field.MethodsRelevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package “Bibliometrix” for bibliometric analysis.ResultsA total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. “chronic pain,” “neuropathic pain,” “psychological pain” are the keywords in the research.ConclusionThis is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.

Satellite Glial Cells Bridge Sensory Neuron Crosstalk in Visceral Pain and Cross-Organ Sensitization.

Following colonic inflammation, the uninjured bladder afferent neurons are also activated. The mechanisms and pathways underlying this sensory neuron cross-activation (from injured neurons to uninjured neurons) are not fully understood. Colonic and bladder afferent neurons reside in the same spinal segments and are separated by satellite glial cells (SGCs) and extracellular matrix in dorsal root ganglia (DRG). SGCs communicate with sensory neurons in a bidirectional fashion. This review summarizes the differentially regulated genes/proteins in the injured and uninjured DRG neurons and explores the role of SGCs in regulation of sensory neuron crosstalk in visceral cross-organ sensitization. The review also highlights the paracrine pathways in mediating neuron-SGC and SGC-neuron coupling with an emphasis on the neurotrophins and purinergic systems. Finally, I discuss the results from recent RNAseq profiling of SGCs to reveal useful molecular markers for characterization, functional study, and therapeutic targets of SGCs. SIGNIFICANCE STATEMENT: Satellite glial cells (SGCs) are the largest glial subtypes in sensory ganglia and play a critical role in mediating sensory neuron crosstalk, an underlying mechanism in colon-bladder cross-sensitization. Identification of novel and unique molecular markers of SGCs can advance the discovery of therapeutic targets in treatment of chronic pain including visceral pain comorbidity.

Biomarker development perspective: Exploring comorbid chronic pain in depression through deep transcranial magnetic stimulation.

Biomarker development perspective: Exploring comorbid chronic pain in depression through deep transcranial magnetic stimulation.

Glial modulators as novel therapeutics for comorbid pain and opioid use disorder.

Chronic pain and opioid use disorder (OUD) are major public health problems, with rising opioid-related overdose deaths linked to increased opioid prescriptions for pain management. Novel treatment approaches for these commonly comorbid disorders are needed. Growing evidence supports a role for glial activation for both chronic pain and substance use disorders, including OUD. This review provides an overview of glial modulators as a novel treatment approach for comorbid pain and OUD. We aim to synthesize clinical studies investigating the efficacy of glial modulators in treating these comorbid disorders. We conducted a literature search of PubMed and Google Scholar databases in October 2023 to identify relevant clinical trials. The included studies varied in terms of patient population, study methodology and outcomes assessed, and were often limited by small sample sizes and other methodological issues. Additionally, several glial modulators have yet to be studied for chronic pain and OUD. Despite these limitations, these studies yielded positive signals that merit further investigation. Both chronic pain and OUD remain significant public health problems, with many treatment challenges. Glial modulators continue to hold promise as novel therapeutics for comorbid pain and OUD, given positive indications that they can improve pain measures, and reduce addiction-related outcomes. As our understanding of the mechanisms underlying the contributions of glial modulators to pain and addiction behaviours deepens, we will be better equipped to identify more specific therapeutic targets for chronic pain and OUD.

Targeting Prefrontal Cortex Dysfunction in Pain.

The prefrontal cortex (PFC) has justifiably become a significant focus of chronic pain research. Collectively, decades of rodent and human research have provided strong rationale for studying the dysfunction of the PFC as a contributing factor in the development and persistence of chronic pain and as a key supraspinal mechanism for pain-induced comorbidities such as anxiety, depression, and cognitive decline. Chronic pain alters the structure, chemistry, and connectivity of PFC in both humans and rodents. In this review, we broadly summarize the complexities of reported changes within both rodent and human PFC caused by pain and offer insight into potential pharmacological and nonpharmacological approaches for targeting PFC to treat chronic pain and pain-associated comorbidities. SIGNIFICANCE STATEMENT: Chronic pain is a significant unresolved medical problem causing detrimental changes to physiological, psychological, and behavioral aspects of life. Drawbacks of currently approved pain therapeutics include incomplete efficacy and potential for abuse producing a critical need for novel approaches to treat pain and comorbid disorders. This review provides insight into how manipulation of prefrontal cortex circuits could address this unmet need of more efficacious and safer pain therapeutics.

Train in Pain: A Review of Exercise Benefits and Application for Individuals With Musculoskeletal Pain

ABSTRACT Exercise is a safe and recommended treatment for individuals experiencing chronic musculoskeletal pain. After receiving medical clearance, strength and conditioning practitioners and clinicians may prescribe exercise for clients with comorbid pain conditions, representing a unique challenge in determining the appropriate exercise prescription. Although exercise is a recommended intervention for pain, pain can also act as a key barrier to exercise participation because of associated increases in pain intensity or location during activity. In addition, biopsychosocial factors integral to the pain experience may affect response to exercise and should be considered when developing an exercise plan of care for this population. Strength and conditioning professionals may also consider the role of contextual factors in the delivery of exercise, such as expectations for pain relief and therapeutic alliance. This narrative review provides an overview of the current evidence regarding exercise for individuals with musculoskeletal pain.

The prevalence and pattern of comorbid long-term conditions with low back pain and osteoarthritis in low- and middle-income countries: a systematic review and meta-analysis

ABSTRACT Chronic musculoskeletal (MSK) pain, specifically low back pain (LBP) and osteoarthritis (OA), are a major cause of global disability, reduced quality of life and high socioeconomic burden. Research in high income countries suggests MSK pain is often comorbid with other long-term conditions / non-communicable diseases (NCDs) including diabetes, hypertension, and cardiovascular disease. However, the epidemiology of comorbid NCDs and MSK pain in low- and middle-income countries (LMICs) is unclear. This systematic review aims to describe the prevalence and pattern of comorbid NCDs in adults with MSK pain in LMICs. Nine databases were searched for epidemiological studies in LMICs (World Bank categories). Paired researchers independently identified studies, extracted data, and completed critical appraisal using Hoy risk of bias tool. Random-effect meta-analysis was used to estimate prevalence of NCDs comorbid with MSK pain. From 2112 citations; 14 studies (n=6093 adults with MSK pain, mean age=46.9years) were included. Overall prevalence of MSK pain with comorbid NCDs was 46.1% (95%CI 32.3 - 59.9). Systemic hypertension had the highest comorbid prevalence with MSK pain (42.6%, 95%CI 25.6-59.6), followed by diabetes (26.7%, 95%CI 16.1-37.3) and mental health conditions (anxiety/depression; 24.9% 95%CI 11.5-38.4). A high proportion of patients with MSK pain in LMICs experience comorbid NCDs. Variable data/population samples, and under-reporting limit accurate capture of prevalence estimates. Understanding the true burden of MSK pain (specifically lower back pain and hip/knee osteoarthritis) and comorbid NCDs is critical to informing effective treatment strategies. The health systems implications of these findings are imperative towards person-centred care, organisation of care and efficient resource utilisation in LMICs.

Examination of pain comorbid diagnoses in the inpatient rehabilitation population across all impairment groups.

Pain is common in inpatient rehabilitation patients; however, the prevalence of pain diagnoses in this population is not well-defined. This study examines comorbid pain diagnoses in inpatient rehabilitation patients across impairment groups. Adult inpatient rehabilitation patients discharged from January 2016 through December 2019 were identified in the Uniform Data System for Medical Rehabilitation® database using a literature-established framework containing ICD-10-CM pain diagnoses. Demographic data, clinical data, and pain diagnoses were compared across the 17 rehabilitation impairment groups. Of 1,925,002 patients identified, 1,347,239 (70.0%) had at least one ICD-10 pain diagnosis. Over half of all patients in each impairment group had at least one pain diagnosis. The most common pain diagnoses were limb/extremity and joint pain, with variation between impairment groups. Female sex and being in the arthritis, major multiple trauma, and pain syndrome impairment groups were associated with a greater odds of a pain diagnosis. Over half of all patients in each rehabilitation impairment group have a pain diagnosis, which varies between impairment groups. Due to the high prevalence of pain diagnoses, a new focus on pain management in inpatient rehabilitation patients is needed. Rehabilitation outcomes may also be affected by pain.

P185 Anatomical patterns of pain in primary care patients with polymyalgia rheumatica compared to the general population

Abstract Background/Aims Polymyalgia rheumatica (PMR) is common in older adults, causing severe pain and stiffness, particularly in the shoulder and hip girdles. A tapered course of glucocorticoids is recommended, but not always straightforward, with frequent symptom recurrence. Reasons are unclear, but partial masking of painful comorbidities (e.g., osteoarthritis) may play a part. Methods 652 people with incident PMR were recruited from English general practice (2012-2014) to a postal survey study (questionnaires at diagnosis, 1, 4, 8, 12, 18, 24, [mean] 61 months). Surveys included a body manikin (front and back views). Participants were asked to shade anywhere they experienced pain >1 day in the last month. 44 mutually exclusive areas were defined as painful or not. For comparison, an age-gender matched random sample of 652 people was selected from a general population survey in North Staffordshire that used the same manikins. Pain prevalence was compared between the 2 studies. Results In the PMR study, surveys were completed by 244 participants at 24 months and 197 at 61 months. Pain was reported in a mean of 17.1 areas at diagnosis (Table). Bilateral shoulder and hip pain were present in the majority at diagnosis (shoulder 81%; hips 59%) and in around a third and a fifth of patients respectively throughout the study. The prevalence of bilateral shoulder and hip pain remained higher than in the general population sample, while unilateral pain in these areas was less common. Bilateral hand (27%) and knee (45%) pain were also common at diagnosis. After 1 month, the mean number of pain areas was 7 - similar to the general population. However, prevalence of bilateral shoulder and hip pain remained higher than the general population throughout follow-up. Unilateral hip and knee pain were persistently less common in those with PMR, whilst unilateral hip pain was more common. Conclusion Bilateral pain was reported more commonly across the disease course in people with PMR than the general population. Causes of pain cannot be accurately attributed, but are likely multifactorial, including PMR disease activity, treatment and painful comorbidities. However, the persistence of bilateral pain suggests untreated PMR symptoms, requiring further research. Disclosure N. Hammad: None. R. Partington: None. S. Hider: None. H. Butt: None. T. Helliwell: None. C. Mallen: None. S. Muller: None.

Chronic idiopathic urinary retention: Comorbidity and outcome in 102 individuals

ObjectivesChronic Idiopathic urinary retention is poorly understood. One small study suggests higher than expected rates of functional neurological disorder and pain comorbidity which may have implications for understanding the disorder. We investigated the frequency of functional neurological disorder, chronic pain other medical and psychiatric comorbidity, triggers of urinary retention, results of urodynamic assessment, medication history, management, and outcome in patients with chronic idiopathic urinary retention. MethodsA consecutive retrospective electronic notes analysis was undertaken of patients with chronic idiopathic urinary retention presenting to a secondary care urology clinic between Jan 2018-Jan 2021, with follow-up to their most recent urological appointment. Results102 patients were identified (mean age of 41.9 years, 98% female). 25% had functional neurological disorder (n = 26), most commonly limb weakness (n = 19, 19%) and functional seizures (n = 16, 16%). Chronic pain (n = 58, 57%) was a common comorbidity. Surgical and medical riggers to urinary retention were found in almost half of patients (n = 49, 48%). 81% of patients underwent urodynamic assessment (n = 83). Most frequently no specific abnormality was reported (n = 30, 29%). Hypertonic urethral sphincter was the most identified urodynamic abnormality (n = 17, 17%). We noted high levels of opioid (n = 50, 49%) and benzodiazepine (n = 27, 26%) use. Urinary retention resolved in only a small number of patients (n = 6, 6%, median follow up 54 months), in three cases spontaneously. ConclusionThis preliminary data suggests idiopathic urinary retention is commonly comorbid with functional neurological disorder, and chronic pain, suggesting shared mechanisms.

Nociplastic pain mechanisms and toll-like receptors as promising targets for its management.

Nociplastic pain, characterized by abnormal pain processing without an identifiable organic cause, affects a significant portion of the global population. Unfortunately, current pharmacological treatments for this condition often prove ineffective, prompting the need to explore new potential targets for inducing analgesic effects in patients with nociplastic pain. In this context, toll-like receptors (TLRs), known for their role in the immune response to infections, represent promising opportunities for pharmacological intervention because they play a relevant role in both the development and maintenance of pain. Although TLRs have been extensively studied in neuropathic and inflammatory pain, their specific contributions to nociplastic pain remain less clear, demanding further investigation. This review consolidates current evidence on the connection between TLRs and nociplastic pain, with a specific focus on prevalent conditions like fibromyalgia, stress-induced pain, sleep deprivation-related pain, and irritable bowel syndrome. In addition, we explore the association between nociplastic pain and psychiatric comorbidities, proposing that modulating TLRs can potentially alleviate both pain syndromes and related psychiatric disorders. Finally, we discuss the potential sex differences in TLR signaling, considering the higher prevalence of nociplastic pain among women. Altogether, this review aims to shed light on nociplastic pain, its underlying mechanisms, and its intriguing relationship with TLR signaling pathways, ultimately framing the potential therapeutic role of TLRs in addressing this challenging condition.

Anterior cingulate cortex and insomnia: A cingulate-striatum connection

Insomnia is an important comorbidity of chronic pain. In this issue of Neuron, Li etal. report that chronic-pain-induced insomnia is mediated by the pyramidal neurons in the anterior cingulate cortex and their dopaminergic projections to the dorsal medial striatum.

Assessing Risk Factors and Comorbidities in the Treatment of Chronic Pain: A Narrative Review.

Chronic pain affects a significant portion of the population globally, making it a leading cause of disability. Understanding the multifaceted nature of chronic pain, its various types, and the intricate relationship it shares with risk factors, comorbidities, and mental health issues like depression and anxiety is critical for comprehensive patient care. Factors such as socioeconomic status (SES), age, gender, and obesity collectively add layers of complexity to chronic pain experiences and pose management challenges. Low SES presents barriers to effective pain care, while gender differences and the prevalence of chronic pain in aging adults emphasize the need for tailored approaches. The association between chronic pain and physical comorbidities like cardiovascular disease, chronic obstructive pulmonary disease (COPD), and diabetes mellitus reveals shared risk factors and further highlights the importance of integrated treatment strategies. Chronic pain and mental health are intricately linked through biochemical mechanisms, profoundly affecting overall quality of life. This review explores pharmacologic treatment for chronic pain, particularly opioid analgesia, with attention to the risk of substance misuse and the ongoing opioid epidemic. We discuss the potential role of medical cannabis as an alternative treatment with a nuanced perspective on its impact on opioid use. Addressing the totality and complexity of pain states is crucial to individualizing chronic pain management. With different types of pain having different underlying mechanisms, considerations should be made when approaching their treatment. Moreover, the synergistic relationship that pain states can have with other comorbidities further complicates chronic pain conditions.

Chronic Pain and Comorbid Depression: A Narrative Review

This narrative review of research includes summaries of 44 papers on the comorbid conditions of chronic pain and depression that were published during the years 2022 and 2023. The publications of this period are primarily randomized controlled trials and systematic reviews/ meta-analyses of randomized controlled trials. Many of these are focused on the prevalence of chronic pain and depression which ranged from 7% to 25% in different age groups and in different countries. Many of the studies addressed the bidirectionality of chronic pain and depression and predictors including stress and inactivity. Ketamine was the most frequent intervention in this literature. And, the most frequent underlying mechanism was involvement of the amygdala. Surprisingly, very few studies focused on youth and on long-term effects of the comorbidity of chronic pain and depression. Methodological problems relate to the variability in the assessments of chronic pain and depression, the selfreport measures and the cross-sectional data that are not definitive about directionality of the chronic pain and depression relationship.

The IMPOWR Network Divided or Single Exposure Study (DOSE) Protocol: A Randomized Controlled Comparison of Once Versus Split Dosing of Methadone for the Treatment of Comorbid Chronic Pain and Opioid Use Disorder.

The Divided or Single Exposure (DOSE) trial is a double-blind, placebo-controlled examination of once versus split dosing of methadone for comorbid pain and opioid use disorder (OUD) among persons receiving methadone for OUD treatment. This multisite trial consists of a 12-week active intervention phase and 6-month follow-up period. Persons receiving methadone who endorse clinically-significant chronic pain are randomized into once-daily dosing or split dosing that is managed remotely via an electronic pillbox. Clinical pain is assessed weekly and using ecological momentary assessments. Experimentally-evoked pain is assessed using a quantitative sensory testing battery. Additional outcomes related to OUD, including withdrawal and craving, are also collected. The study hypothesizes that persons assigned to the split dosing condition will report lower pain and opioid withdrawal relative to persons assigned to the traditional once-daily dosing strategy. Split dosing is a relatively common technique in OUD treatments; therefore, if data support this hypothesis, there is high potential for implementation.

Chronic Pain-Related Cognitive Deficits: Preclinical Insights into Molecular, Cellular, and Circuit Mechanisms.

Cognitive impairment is a common comorbidity of chronic pain, significantly disrupting patients' quality of life. Despite this comorbidity being clinically recognized, the underlying neuropathological mechanisms remain unclear. Recent preclinical studies have focused on the fundamental mechanisms underlying the coexistence of chronic pain and cognitive decline. Pain chronification is accompanied by structural and functional changes in the neural substrate of cognition. Based on the developments in electrophysiology and optogenetics/chemogenetics, we summarized the relevant neural circuits involved in pain-induced cognitive impairment, as well as changes in connectivity and function in brain regions. We then present the cellular and molecular alternations related to pain-induced cognitive impairment in preclinical studies, mainly including modifications in neuronal excitability and structure, synaptic plasticity, glial cells and cytokines, neurotransmitters and other neurochemicals, and the gut-brain axis. Finally, we also discussed the potential treatment strategies and future research directions.

Insula→Amygdala and Insula→Thalamus Pathways Are Involved in Comorbid Chronic Pain and Depression-Like Behavior in Mice.

The comorbidity of chronic pain and depression poses tremendous challenges for the treatment of either one because they exacerbate each other with unknown mechanisms. As the posterior insular cortex (PIC) integrates multiple somatosensory and emotional information and is implicated in either chronic pain or depression, we hypothesize that the PIC and its projections may contribute to the pathophysiology of comorbid chronic pain and depression. We show that PIC neurons were readily activated by mechanical, thermal, aversive, and stressful and appetitive stimulation in naive and neuropathic pain male mice subjected to spared nerve injury (SNI). Optogenetic activation of PIC neurons induced hyperalgesia and conditioned place aversion in naive mice, whereas inhibition of these neurons led to analgesia, conditioned place preference (CPP), and antidepressant effect in both naive and SNI mice. Combining neuronal tracing, optogenetics, and electrophysiological techniques, we found that the monosynaptic glutamatergic projections from the PIC to the basolateral amygdala (BLA) and the ventromedial nucleus (VM) of the thalamus mimicked PIC neurons in pain modulation in naive mice; in SNI mice, both projections were enhanced accompanied by hyperactivity of PIC, BLA, and VM neurons and inhibition of these projections led to analgesia, CPP, and antidepressant-like effect. The present study suggests that potentiation of the PIC→BLA and PIC→VM projections may be important pathophysiological bases for hyperalgesia and depression-like behavior in neuropathic pain and reversing the potentiation may be a promising therapeutic strategy for comorbid chronic pain and depression.

(003) Taking a Step Back for a (Future) Step Forward: Latent Class Analyses of Vulvo-Vaginal Pain Symptoms

Abstract Introduction Persistent genital pain represents a significant health issue among females, with prevalence ranging from 18.5% for lower genital tract discomfort [2], 20% for chronic dyspareunia [3], and 8.3%-27.9% for vulvodynia [6, 7]. Latent class analyses (LCA) allow the identification of groups of individuals who share common symptom profiles and have been used to subgroup vulvodynia patients based on psychological distress and pain sensitivity [1], spontaneous vs provoked pain and pain comorbidities [8] and based only on comorbid pain conditions [5]. Nonetheless, to our knowledge no study has been conducted investigating clusters of symptom-types commonly reported for persistent genital pain. Objective Test for latent classes (clusters) of individuals based on symptom-types profiles among women with vulvar and/or vaginal pain. Methods Self-reports on sexual and genital health were collected from 2199 women through online questionnaires, as part of a larger study. Efforts were made to recruit a heterogenous sample, with an oversampling of females with genito-pelvic pain. Participants were asked about the presence of specific vulvo-vaginal symptoms. Specifically, eight types of vulvar pain (itching, burning, irritation, needles, cut, electric-shock, bladder weight and urinary urgency) and nine types of vaginal pain (dryness, itching, burning, pulsating, needles, cut, electric shocks, spontaneous spasms and spasms at penetration) were measured. LCA were conducted to identify clusters of individuals sharing similar symptom profiles. Analyses were first done including all women with genital pain, then separately for women experiencing only vaginal and only vulvar pain. Results Of the 2199 participants, 1116 (51%) reported experiencing some type of genital pain, with 52% experiencing vulvar and vaginal pain, 17% only vaginal pain and 31% only vulvar pain. Results from LCA analyses suggest that women experiencing vulvo-vaginal pain could best be grouped into 5 clusters, based on the presence of vulvar and vaginal symptoms (Figure 1). Women with only vaginal pain were grouped into 3 clusters based on vaginal symptoms (Figure 2) and women with only vulvar pain were grouped into 3 clusters based on vulvar symptoms (Figure 3). Across all sets of analyses, clusters were clearly differentiated by specific symptoms. Conclusions Although rates of genital pain are high among females, classification of genito-pelvic pain conditions have been, and still are, a matter of debate. While in the DSM-5 vaginismus and dyspareunia were combined into one diagnostic entity, many clinicians continue referring to them as two distinct conditions, creating incoherence in terminology. In addition, chronic vulvar pain (or Vulvodynia) remains often undiagnosed [7], with women waiting an average of a 6-years before receiving a diagnosis [4]. Our data, obtained from a large sample, allowed us to identify profiles based on an empirical/data driven strategy, and provides an innovative approach to defining genital pain conditions. These results offer a starting point to re-think and discuss how diagnoses currently used to categorize female vulvo-vaginal pain can be improved. Longitudinal studies should be conducted to test whether the current strategy of grouping women with vulvo-vaginal pain provides improved diagnoses, more accurate prognoses, or improves our ability to identify patients who will or will not respond to specific treatments. Disclosure No.

The complement system: a potential target for the comorbidity of chronic pain and depression.

The mechanisms of the chronic pain and depression comorbidity have gained significant attention in recent years. The complement system, widely involved in central nervous system diseases and mediating non-specific immune mechanisms in the body, remains incompletely understood in its involvement in the comorbidity mechanisms of chronic pain and depression. This review aims to consolidate the findings from recent studies on the complement system in chronic pain and depression, proposing that it may serve as a promising shared therapeutic target for both conditions. Complement proteins C1q, C3, C5, as well as their cleavage products C3a and C5a, along with the associated receptors C3aR, CR3, and C5aR, are believed to have significant implications in the comorbid mechanism. The primary potential mechanisms encompass the involvement of the complement cascade C1q/C3-CR3 in the activation of microglia and synaptic pruning in the amygdala and hippocampus, the role of complement cascade C3/C3a-C3aR in the interaction between astrocytes and microglia, leading to synaptic pruning, and the C3a-C3aR axis and C5a-C5aR axis to trigger inflammation within the central nervous system. We focus on studies on the role of the complement system in the comorbid mechanisms of chronic pain and depression.