{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:12:14Z","timestamp":1790359934241,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T00:00:00Z","timestamp":1719792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health (NIH)","award":["R01 AT009491-01A1"],"award-info":[{"award-number":["R01 AT009491-01A1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objective: Obesity, characterized by chronic inflammation, may serve as a surrogate marker for more dysfunctional peripheral inflammation, potentially exacerbating FM symptomatology. Given this premise, this study aimed to investigate the effects of obesity as an effect modifier on neural and clinical variables, specifically those indexing pain-compensatory mechanisms in FM symptoms. Methods: A cross-sectional study was conducted with 108 participants who underwent a standardized TMS protocol assessment to measure resting motor threshold (MT), intracortical facilitation (ICF), and intracortical inhibition (ICI). Clinical data were collected using Beck\u2019s Depression Index (BDI), PROMIS, the Brief Pain Inventory (BPI), and conditioned pain modulation (CPM). Linear regression models were used to explore the relationship between these variables while examining Body Mass Index (BMI) as a potential effect modifier. If it was found to be a modifier, we stratified the sample into two groups with a BMI cutoff of 30 and performed another regression model within the subgroups. Results: BMI was identified as an effect modifier in the relationships between ICI and BDI, PROMIS fatigue, and CPM and in MT versus CPM. After stratification, non-obese fibromyalgia subjects demonstrated significant correlations between clinical symptoms and CPM and ICI activity. However, these correlations were absent in the obese group, suggesting obesity disrupts pain mechanisms and their compensatory effects. Higher MT values were associated with weaker endogenous pain control, particularly evident in the obese group. Conclusions: Obesity appears to be a significant effect modifier and delineates two patient groups across multiple clinical and neural assessments of fibromyalgia. Additionally, it suggests a role for obesity in exacerbating fibromyalgia symptoms and disrupting physiological pain-inhibitory mechanisms.<\/jats:p>","DOI":"10.3390\/jcm13133878","type":"journal-article","created":{"date-parts":[[2024,7,1]],"date-time":"2024-07-01T09:06:07Z","timestamp":1719824767000},"page":"3878","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The Impact of Obesity as a Peripheral Disruptor of Brain Inhibitory Mechanisms in Fibromyalgia: A Cross-Sectional Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8467-8454","authenticated-orcid":false,"given":"Walter","family":"Fabris-Moraes","sequence":"first","affiliation":[{"name":"Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA 02129, USA"},{"name":"Faculty of Medicine FMUSP, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guilherme J. M.","family":"Lacerda","sequence":"additional","affiliation":[{"name":"Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA 02129, USA"},{"name":"Faculty of Medicine FMUSP, University of S\u00e3o Paulo, S\u00e3o Paulo 01246-903, SP, Brazil"},{"name":"Instituto de MedicinaF\u00edsica e Reabilita\u00e7\u00e3o, Hospital das Cl\u00ednicas HCFMUSP, Faculdade de Medicina, Universidade de S\u00e3o Paulo, S\u00e3o Paulo 04116-030, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Pacheco-Barrios","sequence":"additional","affiliation":[{"name":"Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA 02129, USA"},{"name":"Unidad de Investigaci\u00f3n para la Generaci\u00f3n y S\u00edntesis de Evidenciasen Salud, Vicerrectorado de Investigaci\u00f3n, Universidad San Ignacio de Loyola, Lima 150114, Peru"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1703-7526","authenticated-orcid":false,"given":"Felipe","family":"Fregni","sequence":"additional","affiliation":[{"name":"Neuromodulation Center, Spaulding Rehabilitation Hospital, Harvard Medical School, Charlestown, MA 02129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1002\/acr.21896","article-title":"Prevalence of fibromyalgia: A population-based study in olmsted county, minnesota, utilizing the rochester epidemiology project","volume":"65","author":"Vincent","year":"2013","journal-title":"Arthritis Care Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1001\/jama.2014.3266","article-title":"Fibromyalgia: A clinical review","volume":"311","author":"Clauw","year":"2014","journal-title":"JAMA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1007\/s11916-013-0356-5","article-title":"Worldwide epidemiology of fibromyalgia","volume":"17","author":"Queiroz","year":"2013","journal-title":"Curr. 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