medRxiv - Pain Medicine最新文献

{"title":"Subcallosal Cingulate structural connectivity as a biomarker for chronic low back pain","authors":"Evangelia Tsolaki, Wenxin Wei, Michael Ward, Ausaf Bari, Nader Pouratian","doi":"10.1101/2024.09.17.24313765","DOIUrl":"https://doi.org/10.1101/2024.09.17.24313765","url":null,"abstract":"Background\u0000Chronic low back pain (CLBP) poses a significant challenge, contributing significantly to the ongoing opioid crisis while also being a leading cause of disability. Although spinal cord stimulation (SCS) stands as the primary FDA-endorsed method for neuromodulatory therapy in CLBP, there remains a subset of patients unresponsive to SCS and others who experience insufficient pain relief over time. In view of the evidence suggesting the critical role of subgenual cingulate cortex (SCC) connectivity in pain processing, in the current study we investigated the role of the baseline SCC structural as a potential neuroimaging predictive biomarker to identify patients that are likely to benefit from SCS. Methods\u0000Diffusion magnetic resonance imaging scans were acquired in 8 patients with CLBP (mean (SD) age = 70 (10) years; 6 female/2 male, 6 UCLA site, 2 UTSW) before their initial SCS trial. Probabilistic tractography from subject-specific anatomically defined SCC seed regions to the ventral striatum (VS), anterior cingulate cortex (ACC), uncinate fasciculus (UCF) and bilateral medial prefrontal cortex (mPFC) was used to calculate FSL structural probabilistic connectivity in the target network. To explore cross-sectional variations in SCC connectivity related to SCS trial response, we employed a general linear model (GLM) using the SCC probability of connectivity as dependent variable, and the response to the SCS trial as independent variable. We used Pearson correlation to evaluate further the relationships between the critical SCC probability of connectivity and the change in VAS score after the SCS trial. Finally, the role of depression in the treatment outcome was evaluated. Results\u0000Responders to SCS had significantly lower ipsilateral SCC connectivity to mPFC (F1,8 =8.19, p = 0.03) and VS (F1,8 =17.48, p=0.01) on the left hemisphere compared to non-responders. Pearson correlation analysis showed that decreased ipsilateral SCC baseline connectivity to left mPFC (p=0.03) and VS (p=0.01) was correlated with higher improvement in VAS scores. The baseline depression severity did not significantly influence the change in VAS score following the SCS trial. On the other hand, baseline SCC-VS connectivity on the left hemisphere was a significant predictor of change in VAS score (p=0.02). Conclusions\u0000Our study highlights the important role of SCC connectivity that can serve as a potential biomarker for CLBP stratification and prediction to SCS treatment. These results can reshape our perspective on CLBP management and can serve as early indicator of response to the treatment providing a personalized approach based on the individual's underlying SCC connectivity.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"45 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Women with fibromyalgia: Insights into behavioral and brain imaging","authors":"Odelia Elkana, Iman Beheshti","doi":"10.1101/2024.09.15.24313716","DOIUrl":"https://doi.org/10.1101/2024.09.15.24313716","url":null,"abstract":"Fibromyalgia (FM) is a chronic condition marked by widespread pain, fatigue, sleep problems, cognitive decline, and other symptoms. Despite extensive research, the pathophysiology of FM remains poorly understood, complicating diagnosis and treatment, which often relies on self-report questionnaires. This study explored structural and functional brain changes in women with FM, identified potential biomarkers, and examined their relationship with FM severity. MRI data from 33 female FM patients and 33 matched healthy controls were utilized, focusing on T1-weighted MRI and resting-state fMRI scans. Functional connectivity (FC) analysis was performed using a machine learning framework to differentiate FM patients from healthy controls and predict FM symptom severity. No significant differences were found in brain structural features, such as gray matter volume, white matter volume, deformation-based morphometry, and cortical thickness. However, significant differences in FC were observed between FM patients and healthy controls, particularly in the default mode network (DMN), somatomotor network (SMN), visual network (VIS), and dorsal attention network (DAN). The FC metrics were significantly associated with FM severity. Our prediction model differentiated FM patients from healthy controls with an area under the curve of 0.65. FC measures accurately estimated FM symptom severities with a significant correlation (r = 0.45, p = 0.007). Functional connections in the DMN, VIS, and DAN were crucial in determining FM severity. These findings suggest that integrating brain FC measurements could serve as valuable biomarkers for early detection of FM and predicting FM symptom severity, improving diagnostic accuracy and facilitating the development of targeted therapeutic strategies.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"208 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142262384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards validation of clinical measures to discriminate between nociceptive, neuropathic and nociplastic pain: cluster analysis of a cohort with chronic musculoskeletal pain","authors":"Paul W Hodges, Raimundo Sanchez, Shane Pritchard, Adam Turnbull, Andrew Hahne, Jon Ford","doi":"10.1101/2024.08.13.24311924","DOIUrl":"https://doi.org/10.1101/2024.08.13.24311924","url":null,"abstract":"The International Association for the Study of Pain defines three pain types presumed to involve different mechanisms - nociceptive, neuropathic and nociplastic. Based on the hypothesis that these pain types should guide matching of patients with treatments, work has been undertaken to identify features to discriminate between them for clinical use. This study aimed to evaluate the validity of these features to discriminate between pain types. Subjective and physical features were evaluated in a cohort of 350 individuals with chronic musculoskeletal pain attending a chronic pain management program. Analysis tested the hypothesis that, if the features nominated for each pain type represent 3 different groups, then (i) cluster analysis should identify 3 main clusters of patients, (ii) these clusters should align with the pain type allocated by an experienced clinician, (iii) patients within a cluster should have high expression of the candidate features proposed to assist identification of that pain type. Supervised machine learning interrogated features with the greatest and least importance for discrimination; and probabilistic analysis probed the potential for coexistence of multiple pain types. Results confirmed that data could be best explained by 3 clusters, clusters were characterized by a priori specified features, and agreed with the designation of the experienced clinical with 82% accuracy. Supervised analysis highlighted features that contributed most and least to the classification of pain type and probabilistic analysis reinforced the presence of mixed pain types. These findings support the foundation for further refinement of a clinical tool to discriminate between pain types.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"116 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142175734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain-related white-matter changes following mild traumatic brain injury: A longitudinal diffusion tensor imaging pilot study","authors":"Ho-Ching Yang, Tyler Nguyen, Fletcher A White, Kelly M Naugle, Yu-Chien Wu","doi":"10.1101/2024.08.05.24310944","DOIUrl":"https://doi.org/10.1101/2024.08.05.24310944","url":null,"abstract":"Post-traumatic headache (PTH) is a common consequence of mild traumatic brain injury (mTBI), significantly impacting an\u0000individual's quality of life and rehabilitation. However, the underlying neuropathogenesis of PTH remains poorly understood. This\u0000study utilized diffusion tensor imaging (DTI) to detect microstructural brain alterations in mTBI participants with or at risk of\u0000developing PTH. The current study investigated associations between early DTI metrics (1-month postinjury), pain sensitivity\u0000(quantitative sensory tests), and psychological assessments (1-month and 6-months postinjury) to identify differences between mTBI\u0000(n=12) and healthy controls (HC; n=10). Abnormalities in mean axial diffusivity in the forceps major were observed in mTBI relative\u0000to HCs at 1-month postinjury (p=0.02). Within the mTBI group, DTI metrics at 1-month postinjury were significantly associated\u0000(p<0.05) with pain-related measures and psychological outcomes at 6-months postinjury. Notably, the associations between early\u0000DTI metrics and later pain-related measures exhibited significant group differences in right sagittal stratum (p<0.01), white\u0000matter tract in left insula (p<0.04), and left superior longitudinal fasciculus (p<0.05). In conclusion, these findings indicate that DTI\u0000metrics can be used to predict pain and psychological measures in mTBI, suggesting an important role of white matter\u0000microstructure in PTH following mTBI.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141942631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating the Opioid Epidemic: The Role of Cannabinoids in Chronic Pain Management - A Systematic Review and Meta-Analysis of Clinical Evidence and Mechanisms","authors":"Julian Y. V. Borges","doi":"10.1101/2024.07.14.24310378","DOIUrl":"https://doi.org/10.1101/2024.07.14.24310378","url":null,"abstract":"Abstract\u0000Background and Objectives: As the medical community seeks alternative pain management strategies, cannabinoids have emerged as a potential option. This review discusses the role of cannabinoids in chronic pain management and their potential as an alternative treatment in pain medicine, focusing on efficacy, safety, and possible opioid reduction. The objectives are to evaluate the efficacy and safety of cannabinoids in chronic pain management, explore their potential to reduce opioid use, and identify the mechanisms by which cannabinoids exert their analgesic effects. Additionally, the review seeks to highlight the clinical implications and limitations of using cannabinoids as an alternative to opioids. Methods: A comprehensive literature review and meta-analysis were conducted, focusing on studies from PubMed, MEDLINE, and Cochrane, focusing on various types of studies. Data were extracted and analyzed to assess the efficacy, safety, and potential opioid-sparing effects of cannabinoids. Mechanistic insights were also explored to understand how cannabinoids modulate pain. Results: Cannabinoids have shown efficacy in managing chronic pain, with evidence indicating their ability to reduce pain and improve quality of life. Studies suggest that cannabinoids can provide significant analgesic effects, although there is variability in efficacy across trials. Findings also show that Cannabinoids modulate pain through the endocannabinoid system, which plays a crucial role in pain perception and inflammation. Limitations: The variability in efficacy across studies suggests a need for standardized formulations and dosing regimens. Long-term effects of cannabinoid use are not fully understood, necessitating further research. More high-quality trials are needed to confirm findings and address potential biases. Conclusion: Cannabinoids offer a promising alternative for chronic pain management, with the potential to mitigate the opioid epidemic. Integrating cannabinoids into clinical practice, guided by evidence-based protocols, can provide a safer and effective approach to chronic pain management.\u0000Keywords: Opioid Epidemic, Chronic Pain Management, Cannabinoids, Medical Cannabis, Pain Relief, Opioid-Sparing Effects, Endocannabinoid System, Clinical Practice, Analgesia, Alternative Therapies","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"194 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141863805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"National Assessment on the Frequency of Pain Medication Prescribed for Intrauterine Device Insertion Procedures within the Veterans Affairs Health Care System","authors":"Anna Ware, Terri Blumke, Peter J Hoover, Zachary P Veigulis, Jacqueline M Ferguson, Malvika Pillai, Thomas Osborne","doi":"10.1101/2024.07.25.24311008","DOIUrl":"https://doi.org/10.1101/2024.07.25.24311008","url":null,"abstract":"Background: The intrauterine device (IUD) is a highly effective form of long-acting reversible contraception, widely recognized for its convenience and efficacy. Despite its benefits, many patients report moderate to severe pain during and after their IUD insertion procedure. Furthermore, reports suggest significant variability in pain control medications, including no adequate pain medication. The aim of this evaluation was to assess the pharmaceutical pain medication types, proportions, and trends related to IUD insertion procedures within the Veterans Health Administration (VHA).\u0000Methods: IUD insertion procedures documented in the VA electronic health record were assessed from 1/1/2018 to 10/13/2023. Descriptive statistics described patient and facility characteristics while annual trends were assessed using linear regression.\u0000Results: Out of the 28,717 procedures captured, only 11.4% had any form of prescribed pain medication identified. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) were the most frequently prescribed pain medication category (8.3%), with ibuprofen being the most common pain medication overall (6.1%). Over the assessment period, there was an average annual increase of 0.52% (p=0.038) of procedures with prescribed pain medication, increasing from 10.3% in 2018 to 13.3% in 2023.\u0000Conclusions: Although IUD insertion procedures have been seeing an increase in prescribed pain medication, the overall proportion remains disproportionality low relative to the pain experienced. Additionally, when pain interventions were initiated, they disproportionally utilized medication that have been shown to be ineffective. The intent of the work is that the information will help guide data driven pain medication strategies for patients undergoing IUD insertion procedures within the VHA.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141780838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New-onset chronic musculoskeletal pain following COVID-19 infection fulfil the Fibromyalgia clinical syndrome criteria","authors":"Omar Khoja, Matthew Mulvey, Sarah Astill, Ai Lyn Tan, Manoj Sivan","doi":"10.1101/2024.07.10.24310234","DOIUrl":"https://doi.org/10.1101/2024.07.10.24310234","url":null,"abstract":"Background: New-onset chronic musculoskeletal (MSK) pain (> 3 months duration) is one of the commonest persistent symptoms of Post-COVID syndrome (PCS). There is emerging evidence that the chronic MSK pain and associated symptoms in PCS have similarities to Fibromyalgia Syndrome (FMS). This study aimed to characterise PCS related new-onset chronic MSK pain and its overlap with Fibromyalgia Syndrome (FMS). Methods: Patients with new-onset chronic MSK pain following COVID-19 infection were enrolled and the nature of pain and associated symptoms captured using the C19-YRS (Yorkshire Rehabilitation Scale). FMS assessment was conducted as part of standard clinical examination using the American College of Rheumatology (ACR) 2010 criteria. Diagnosis of FMS was made when they meet the standard criteria of (1) Widespread Pain Index (WPI) ≥ 7 and Symptoms Severity (SS) score ≥ 5, or WPI is 3-6 and SS score ≥ 9, (2) symptoms have been present at a similar level for at least 3 months, and (3) the patient does not have a disorder that would otherwise explain the symptoms.\u0000Results: Eighteen patients, twelve of whom were female, with an average age of 49.6 (SD 11.8) years and a Body Mass Index of 31.7 (SD 8.6) were enrolled. The average duration of symptoms from COVID-19 infection to assessment was 27.9 (SD 6.97) months. The new-onset chronic pain was widespread, primarily manifesting as muscle pain. Thirteen (72.2%) patients met the diagnostic criteria for FMS, with an average WPI score of 8.8 and an average SS score of 8.2, indicating a high level of pain and significant adverse impact on their quality of life.\u0000Conclusion: The study found that 72.2% of the patients with new-onset chronic MSK pain following COVID-19 infection met the criteria for FMS. These findings support the hypothesis that FMS may develop as a long-term sequela of a viral infection, underscoring the need for further research into post-viral long-term conditions.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141610824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BLOOD PROTEOMICS AND PAIN - A TRANSLATIONAL STUDY TO PROGNOSTICATE PAIN PHENOTYPES AND ASSESS NEW BIOMARKERS FOR PREVENTING PAIN IN HUMANS","authors":"Daniel Segelcke, Julia R Sondermann, Christin Kappert, Bruno Pradier, Dennis Goerlich, Manfred Fobker, Jan Vollert, Peter K. Zahn, Manuela Schmidt, Esther M. Pogatzki-Zahn","doi":"10.1101/2024.07.04.24309933","DOIUrl":"https://doi.org/10.1101/2024.07.04.24309933","url":null,"abstract":"Personalized strategies in pain management and prevention should be based on individual risk factors as early as possible, but the factors most relevant are not yet known. An innovative approach would be to integrate multi-modal risk factors, including blood proteomics, in predicting high pain responders and using them as targets for personalized treatment options. Here, we determined and mapped multi-modal factors to prognosticate a phenotype with high risk of developing pain and hyperalgesia after an experimental incision in humans. We profiled unbiased blood plasma proteome signature of 26 male volunteers, assessed psychophysical and psychological aspects before incision injury. Outcome measures were pain intensity ratings and the extent of the area of hyperalgesia to mechanical stimuli surrounding the incision as a proxy for central sensitization. Phenotype-based stratification resulted in the identification of low- and high-responders for the two different outcome measures. Logistic regression analysis revealed prognostic potential for blood plasma proteins and for psychophysical and psychological parameters. The combination of certain parameters increased the prognostic accuracy for both outcome measures, exceeding 97%. In high-responders, term-term-interaction network analysis showed a proteome signature of a low-grade inflammation reaction. Intriguingly, in silico drug repurposing indicates a high potential for specific antidiabetic and anti-inflammatory drugs already available. In conclusion, we show an integrated pipeline that provides a valuable resource for patient stratification and the identification of (i) multi-feature prognostic models, (ii) treatment targets, and (iii) mechanistic correlates that may be relevant for individualized management of pain and its long-term consequences.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-creating a Choosing Wisely Leaflet Supporting the Reduction of Imaging Usage in Low Back Pain Management - A Multi-Method Study.","authors":"Chris Djurtoft, Edel O'Hagan, Monika Deleuran Laursen, Lars Lejbølle, Mia Bisgaard Jensen, Simon Kristoffer Johansen, Kristian Damgaard Lyng, Morten Hoegh, Negar Pourbordbari, Malene Kjær Bruun, Bettina Eiger, Jesper Bie Larsen, Michael Skovdal Rathleff","doi":"10.1101/2024.07.02.24309693","DOIUrl":"https://doi.org/10.1101/2024.07.02.24309693","url":null,"abstract":"Introduction: Low back pain is a global health challenge with negative consequences for both individuals and healthcare systems. The 'Choosing Wisely' initiative aims to improve communication between patients and clinicians to promote informed healthcare decisions while avoiding unnecessary tests and treatments. The objective of this project is to co-create an information resource in the form of a leaflet, to be distributed in clinical settings, websites or social media targeting people with low back pain. Methods: This multi-method study was conducted in four stages: literature search, input from practice consultants, program theory development, and think-aloud interviews with people experiencing low back pain. Each stage was followed by a consensus meeting in which the steering group refined the leaflet based on the emerging knowledge. Results: The literature search highlighting patients' need for understandable information about diagnosis, treatment options, and self-management strategies. Practice consultants emphasized concise, relatable content. The program theory identified potential mechanisms and design targets for content creation, development, and implementation of the leaflet, such as addressing patient concerns, reducing diagnostic uncertainty, offering insights into management options, and validation. Think-aloud interviews with 18 people living with low back pain informed the iteration of the leaflet, enhancing language clarification and content comprehension. Conclusion: We co-created a new Choosing Wisely leaflet, created with end-users in mind, specifically focused on reducing unnecessary imaging for low back pain. Valuable feedback from end-users prompted significant revisions, underscoring the importance of involving multiple end-user viewpoints into the creation process.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No evidence for causal effects of C-reactive protein (CRP) on chronic pain conditions: a Mendelian randomization study","authors":"Pradeep Suri, Yakov A Tsepilov, Elizaveta E. Elgaeva, Frances MK Williams, Maxim Freydin, Ian Stanaway","doi":"10.1101/2024.07.03.24309700","DOIUrl":"https://doi.org/10.1101/2024.07.03.24309700","url":null,"abstract":"Objective: We conducted a Mendelian randomization (MR) study to examine causal associations of C-reactive protein (CRP) with (1) spinal pain; (2) extent of multisite chronic pain; and (3) chronic widespread musculoskeletal pain. Design: Two-sample MR study. Setting/Subjects: We used summary statistics from publicly available genome-wide association studies (GWAS) conducted in multiple cohorts and biobanks. Genetic instrumental variables were taken from an exposure GWAS of CRP (n=204,402). Outcome GWASs examined spinal pain (n=1,028,947), extent of multisite chronic pain defined as the number of locations with chronic pain (n=387,649), and chronic widespread pain (n=249,843). Methods: We examined MR evidence for causal associations using inverse-variance weighted (IVW) analysis and sensitivity analyses using other methods. We calculated odds ratios (ORs), 95% confidence intervals (95% CIs), and p-values, using a Bonferroni correction (p<0.0166) to account for 3 primary comparisons. Results: Greater serum CRP (mg/L) was not significantly causally associated with spinal pain (OR=1.04, 95% CI 1.00-1.08; p=0.07) in IVW analysis. Greater serum CRP also showed no significant causal association with extent of multisite chronic pain in IVW analysis (beta coefficient= 0.014, standard error=0.011; p=0.19). CRP also showed no significant causal association with chronic widespread pain in IVW analysis (OR=1.00, 95% CI 1.00-1.00; p=0.75). All secondary and sensitivity analyses also showed no significant associations. Conclusions: This MR study found no causal association of CRP on spinal pain, the extent of chronic pain, or chronic widespread pain. Future studies examining mechanistic biomarkers for pain conditions should consider other candidates besides CRP.","PeriodicalId":501393,"journal":{"name":"medRxiv - Pain Medicine","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141570105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}