{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:45:45Z","timestamp":1785321945035,"version":"3.55.0"},"reference-count":87,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T00:00:00Z","timestamp":1732924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah","award":["1727-828-2024"],"award-info":[{"award-number":["1727-828-2024"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Fibromyalgia (FM) is a chronic and debilitating condition characterized by diffuse pain, often associated with symptoms such as fatigue, cognitive disturbances, and mood disorders. Metformin, an oral hypoglycemic agent, has recently gained attention for its potential benefits beyond glucose regulation. It has shown promise in alleviating neuropathic and inflammatory pain, suggesting that it could offer a novel approach to managing chronic pain conditions like FM. This study aimed to further explore metformin\u2019s analgesic potential by evaluating its effects in an experimental FM model induced by reserpine in both male and female mice. After the administration of 200 mg\/kg metformin to male and female mice, the FM-related symptoms were assessed, including mechanical allodynia, thermal hyperalgesia, and depressive-like behaviors. A histological examination of the thalamus, hippocampus, and spinal cord was conducted using haematoxylin and eosin staining. The neurotransmitter and proinflammatory cytokines levels were measured in the brains and spinal cords. Our results have shown that metformin treatment for seven days significantly reversed these FM-like symptoms, reducing pain sensitivity and improving mood-related behaviors in both the male and female mice. Additionally, metformin exhibited neuroprotective effects, mitigating reserpine-induced damage in the hippocampus, thalamus, and spinal cord. It also significantly lowered the levels of the proinflammatory cytokine interleukin 1-beta (IL-1\u03b2) in the brain and spinal cord. Notably, metformin modulated the neurotransmitter levels differently between the sexes, decreasing glutamate and increasing serotonin and norepinephrine in the male mice, but not in the females. These findings underscore metformin\u2019s potential as an alternative therapy for FM, with sex-specific differences suggesting distinct mechanisms of action.<\/jats:p>","DOI":"10.3390\/cells13231986","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T06:58:58Z","timestamp":1733122738000},"page":"1986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Antinociceptive Effects and Sex-Specific Neurotransmitter Modulation of Metformin in a Mouse Model of Fibromyalgia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7076-8491","authenticated-orcid":false,"given":"Hanin Abdulbaset","family":"AboTaleb","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4223-6957","authenticated-orcid":false,"given":"Hani A.","family":"Alturkistani","sequence":"additional","affiliation":[{"name":"Department of Clinical Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah 22252, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0398-0297","authenticated-orcid":false,"given":"Gamal S.","family":"Abd El-Aziz","sequence":"additional","affiliation":[{"name":"Department of Clinical Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah 22252, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5794-9976","authenticated-orcid":false,"given":"Emad A.","family":"Hindi","sequence":"additional","affiliation":[{"name":"Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Clinical Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah 22252, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9459-0459","authenticated-orcid":false,"given":"Mervat M.","family":"Halawani","sequence":"additional","affiliation":[{"name":"Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Clinical Anatomy, Faculty of Medicine, King Abdulaziz University, Jeddah 22252, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3071-6854","authenticated-orcid":false,"given":"Mona Ali","family":"Al-Thepyani","sequence":"additional","affiliation":[{"name":"Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Department of Chemistry, College of Sciences & Arts, King Abdulaziz University, Rabigh 21911, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9411-3609","authenticated-orcid":false,"given":"Badrah S.","family":"Alghamdi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia"},{"name":"Neuroscience and Geroscience Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/s41584-020-00506-w","article-title":"Fibromyalgia: An update on clinical characteristics, aetiopathogenesis and treatment","volume":"16","author":"Giorgi","year":"2020","journal-title":"Nat. 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