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Open AccessArticle

Melatonin Plus Folic Acid Treatment Ameliorates Reserpine-Induced Fibromyalgia: An Evaluation of Pain, Oxidative Stress, and Inflammation

Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, n 31, 98166 Messina, Italy
Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd, St. Louis, MO 63104, USA
Authors to whom correspondence should be addressed.
These authors equally contributed to this work.
Antioxidants 2019, 8(12), 628;
Received: 24 October 2019 / Revised: 27 November 2019 / Accepted: 5 December 2019 / Published: 6 December 2019
Background: Fibromyalgia is a chronic condition characterized by increased sensory perception of pain, neuropathic/neurodegenerative modifications, oxidative, and nitrosative stress. An appropriate therapy is hard to find, and the currently used treatments are able to target only one of these aspects. Methods: The aim of this study is to investigate the beneficial effects of melatonin plus folic acid administration in a rat model of reserpine-induced fibromyalgia. Sprague–Dawley male rats were injected with 1 mg/kg of reserpine for three consecutive days and later administered with melatonin, folic acid, or both for twenty-one days. Results: Administration of reserpine led to a significant decrease in the nociceptive threshold as well as a significant increase in depressive-like symptoms. These behavioral changes were accompanied by increased oxidative and nitrosative stress. Lipid peroxidation was significantly increased, as well as nitrotyrosine and PARP expression, while superoxide dismutase, nonprotein thiols, and catalase were significantly decreased. Endogenously produced oxidants species are responsible for mast cell infiltration, increased expression pro-inflammatory mediators, and microglia activation. Conclusion: Melatonin plus acid folic administration is able to ameliorate the behavioral defects, oxidative and nitrosative stress, mast cell infiltration, inflammatory mediators overexpression, and microglia activation induced by reserpine injection with more efficacy than their separate administration. View Full-Text
Keywords: fibromyalgia; oxidative stress; pain fibromyalgia; oxidative stress; pain
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Fusco, R.; Siracusa, R.; D’Amico, R.; Peritore, A.F.; Cordaro, M.; Gugliandolo, E.; Crupi, R.; Impellizzeri, D.; Cuzzocrea, S.; Di Paola, R. Melatonin Plus Folic Acid Treatment Ameliorates Reserpine-Induced Fibromyalgia: An Evaluation of Pain, Oxidative Stress, and Inflammation. Antioxidants 2019, 8, 628.

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