{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T20:08:02Z","timestamp":1784837282506,"version":"3.55.0"},"reference-count":83,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T00:00:00Z","timestamp":1575590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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\u2013Dawley 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.<\/jats:p>","DOI":"10.3390\/antiox8120628","type":"journal-article","created":{"date-parts":[[2019,12,6]],"date-time":"2019-12-06T10:41:44Z","timestamp":1575628904000},"page":"628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Melatonin Plus Folic Acid Treatment Ameliorates Reserpine-Induced Fibromyalgia: An Evaluation of Pain, Oxidative Stress, and Inflammation"],"prefix":"10.3390","volume":"8","author":[{"given":"Roberta","family":"Fusco","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba","family":"Siracusa","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0389-3871","authenticated-orcid":false,"given":"Ramona","family":"D\u2019Amico","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio Filippo","family":"Peritore","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-0043","authenticated-orcid":false,"given":"Marika","family":"Cordaro","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6840-3154","authenticated-orcid":false,"given":"Enrico","family":"Gugliandolo","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7629-3132","authenticated-orcid":false,"given":"Rosalia","family":"Crupi","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Impellizzeri","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6131-3690","authenticated-orcid":false,"given":"Salvatore","family":"Cuzzocrea","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"},{"name":"Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, 1402 South Grand Blvd, St. Louis, MO 63104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6725-8581","authenticated-orcid":false,"given":"Rosanna","family":"Di Paola","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D\u2019Alcontres, n 31, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/art.1780330203","article-title":"The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee","volume":"33","author":"Wolfe","year":"1990","journal-title":"Arthritis Rheum"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"457","DOI":"10.4065\/mcp.2010.0738","article-title":"FibroCollaborative, Improving the recognition and diagnosis of fibromyalgia","volume":"86","author":"Arnold","year":"2011","journal-title":"Mayo Clin. Proc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00482-012-1169-x","article-title":"Das Fibromyalgiesyndrom","volume":"26","author":"Eich","year":"2012","journal-title":"Der Schmerz"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.3899\/jrheum.100594","article-title":"Fibromyalgia criteria and severity scales for clinical and epidemiological studies: A modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia","volume":"38","author":"Wolfe","year":"2011","journal-title":"J. Rheumatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.semarthrit.2007.09.003","article-title":"Central sensitivity syndromes: A new paradigm and group nosology for fibromyalgia and overlapping conditions, and the related issue of disease versus illness","volume":"37","author":"Yunus","year":"2008","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_6","first-page":"20","article-title":"Fibromyalgia and cognition","volume":"69","author":"Glass","year":"2008","journal-title":"J. Clin. Psychiatry"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1177\/1099800411424204","article-title":"Psychoneuroimmunological relationships in women with fibromyalgia","volume":"15","author":"Menzies","year":"2013","journal-title":"Biol. Res. Nurs."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1016\/j.amjmed.2009.09.008","article-title":"Pathophysiology of fibromyalgia","volume":"122","author":"Bradley","year":"2009","journal-title":"Am. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.biopsycho.2011.02.002","article-title":"Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders","volume":"87","author":"Tak","year":"2011","journal-title":"Biol. Psychol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1177\/0004563213506413","article-title":"Altered profile of chemokines in fibromyalgia patients","volume":"51","author":"Garcia","year":"2014","journal-title":"Ann. Clin. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Behm, F.G., Gavin, I.M., Karpenko, O., Lindgren, V., Gaitonde, S., Gashkoff, P.A., and Gillis, B.S. (2012). Unique immunologic patterns in fibromyalgia. BMC Clin. Pathol., 12.","DOI":"10.1186\/1472-6890-12-25"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Uceyler, N., Hauser, W., and Sommer, C. (2011). Systematic review with meta-analysis: Cytokines in fibromyalgia syndrome. BMC Musculoskelet. Disord., 12.","DOI":"10.1186\/1471-2474-12-245"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.imlet.2014.01.009","article-title":"Fibromyalgia and cytokines","volume":"161","author":"Howard","year":"2014","journal-title":"Immunol. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.7754\/Clin.Lab.2014.131017","article-title":"Serum ischemia-modified albumin and malondialdehyde levels and superoxide dismutase activity in patients with fibromyalgia","volume":"60","author":"Toker","year":"2014","journal-title":"Clin. Lab."},{"key":"ref_15","first-page":"1199","article-title":"Evaluation of some antioxidant enzyme activities (SOD and GPX) and their polymorphisms (MnSOD2 Ala9Val, GPX1 Pro198Leu) in fibromyalgia","volume":"18","author":"Akbas","year":"2014","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1007\/s00296-003-0427-8","article-title":"Free radicals and antioxidants in primary fibromyalgia: An oxidative stress disorder?","volume":"25","author":"Bagis","year":"2005","journal-title":"Rheumatol. Int."},{"key":"ref_17","first-page":"981565","article-title":"Fibromyalgia: When Distress Becomes (Un) sympathetic Pain","volume":"2012","year":"2012","journal-title":"Pain Res. Treat."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nrrheum.2016.26","article-title":"Neuroinflammation in fibromyalgia and CRPS: Top-down or bottomup?","volume":"12","author":"Littlejohn","year":"2016","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4081\/reumatismo.2014.767","article-title":"Pain in fibromyalgia and related conditions","volume":"66","author":"Cassisi","year":"2014","journal-title":"Reumatismo"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/B978-0-7020-4086-3.00033-3","article-title":"Fibromyalgia","volume":"Volume 119","author":"Sumpton","year":"2014","journal-title":"Handbook of Clinical Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrrheum.2015.56","article-title":"The role of sleep in pain and fibromyalgia","volume":"11","author":"Choy","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.mito.2015.01.010","article-title":"Oxidative stress, mitochondrial dysfunction and, inflammation common events in skin of patients with Fibromyalgia","volume":"21","author":"Bullon","year":"2015","journal-title":"Mitochondrion"},{"key":"ref_23","first-page":"S109","article-title":"Brain imaging in fibromyalgia syndrome","volume":"29","author":"Staud","year":"2011","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1080\/14737175.2016.1207531","article-title":"Recent strategies for drug development in fibromyalgia syndrome","volume":"16","author":"Blumenthal","year":"2016","journal-title":"Expert Rev. Neurother."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40122-016-0049-y","article-title":"Melatonin in Chronic Pain Syndromes","volume":"5","author":"Danilov","year":"2016","journal-title":"Pain Ther."},{"key":"ref_26","first-page":"S14","article-title":"The involvement of melatonin in the clinical status of patients with fibromyalgia syndrome","volume":"33","author":"Pernambuco","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"T187","DOI":"10.1530\/JOE-15-0119","article-title":"60 YEARS OF NEUROENDOCRINOLOGY: Regulation of mammalian neuroendocrine physiology and rhythms by melatonin","volume":"226","author":"Johnston","year":"2015","journal-title":"J. Endocrinol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1152\/physiol.00011.2014","article-title":"Melatonin: Exceeding expectations","volume":"29","author":"Reiter","year":"2014","journal-title":"Physiology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/jpi.12267","article-title":"Melatonin: An ancient molecule that makes oxygen metabolically tolerable","volume":"59","author":"Manchester","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.pain.2007.01.025","article-title":"Oral and spinal melatonin reduces tactile allodynia in rats via activation of MT2 and opioid receptors","volume":"132","year":"2007","journal-title":"Pain"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1111\/aas.12747","article-title":"The analgesic effects of exogenous melatonin in humans","volume":"60","author":"Andersen","year":"2016","journal-title":"Acta Anaesthesiol. Scand."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1007\/s00296-005-0079-y","article-title":"Antioxidant status, lipid peroxidation and nitric oxide in fibromyalgia: Etiologic and therapeutic concerns","volume":"26","author":"Ozgocmen","year":"2006","journal-title":"Rheumatol. Int."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1093\/nutrit\/nuw053","article-title":"Role of folic acid in nitric oxide bioavailability and vascular endothelial function","volume":"75","author":"Stanhewicz","year":"2017","journal-title":"Nutr. Rev."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1079\/BJN2001478","article-title":"Folate protects against oxidative modification of human LDL","volume":"86","author":"Nakano","year":"2001","journal-title":"Br. J. Nutr."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1016\/S0891-5849(01)00543-3","article-title":"Free radical scavenging behavior of folic acid: Evidence for possible antioxidant activity","volume":"30","author":"Joshi","year":"2001","journal-title":"Free Radic. Biol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S0891-5849(97)00097-X","article-title":"Vitamins C, E and A and heme oxygenase in rats fed methyl\/folate-deficient diets","volume":"23","author":"Henning","year":"1997","journal-title":"Free Radic. Biol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/0021-9150(95)06724-8","article-title":"Pro-thrombotic effects of a folic acid deficient diet in rat platelets and macrophages related to elevated homocysteine and decreased n-3 polyunsaturated fatty acids","volume":"121","author":"Durand","year":"1996","journal-title":"Atherosclerosis"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.pain.2009.05.024","article-title":"Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia","volume":"146","author":"Nagakura","year":"2009","journal-title":"Pain"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1017\/S0007114500000222","article-title":"High-dose folic acid supplementation in rats: Effects on gestation and the methionine cycle","volume":"83","author":"Achon","year":"2000","journal-title":"Br. J. Nutr."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Favero, G., Trapletti, V., Bonomini, F., Stacchiotti, A., Lavazza, A., Rodella, L.F., and Rezzani, R. (2017). Oral Supplementation of Melatonin Protects against Fibromyalgia-Related Skeletal Muscle Alterations in Reserpine-Induced Myalgia Rats. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18071389"},{"key":"ref_41","unstructured":"Bhalala, O.G., and de Morree, A. (2016). Assessment of Mechanical Allodynia in Rats Using the Electronic Von Frey Test. J. Neurosci."},{"key":"ref_42","first-page":"382","article-title":"Co-micronized palmitoylethanolamide\/polydatin treatment causes endometriotic lesion regression in a rodent model of surgically induced endometriosis","volume":"7","author":"Fusco","year":"2016","journal-title":"Front. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/0014-2999(78)90118-8","article-title":"Behavioural despair in rats: A new model sensitive to antidepressant treatments","volume":"47","author":"Porsolt","year":"1978","journal-title":"Eur. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/0166-4328(96)00067-8","article-title":"Detection of serotonergic and noradrenergic antidepressants in the rat forced swimming test: The effects of water depth","volume":"73","author":"Detke","year":"1996","journal-title":"Behav. Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/0005-2760(65)90118-9","article-title":"Mechanisms of Lipid Peroxide Formation in Tissues. Role of Metals and Haematin Proteins in the Catalysis of the Oxidation Unsaturated Fatty Acids","volume":"98","author":"Wills","year":"1965","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1159\/000136485","article-title":"Bromobenzene-induced liver necrosis. Protective role of glutathione and evidence for 3,4-bromobenzene oxide as the hepatotoxic metabolite","volume":"11","author":"Jollow","year":"1974","journal-title":"Pharmacology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/0003-9861(78)90479-4","article-title":"Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase","volume":"186","author":"Kono","year":"1978","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_48","unstructured":"Claiborne, A. (1985). Handbook of Methods for Oxygen Radical Research, CRC Press."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1016\/j.psyneuen.2011.04.012","article-title":"Curcumin ameliorates reserpine-induced pain-depression dyad: Behavioural, biochemical, neurochemical and molecular evidences","volume":"36","author":"Arora","year":"2011","journal-title":"Psychoneuroendocrinology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S37","DOI":"10.1016\/j.freeradbiomed.2017.04.144","article-title":"Anti-oxidant and anti-inflammatory effects of a flavonoid-rich extract from orange juice in experimental colitis","volume":"108","author":"Fusco","year":"2017","journal-title":"Free Radic. Biol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.phrs.2019.01.041","article-title":"Formyl peptide receptor 1 signalling promotes experimental colitis in mice","volume":"141","author":"Fusco","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1744-8069-8-32","article-title":"Patients with fibromyalgia display less functional connectivity in the brain\u2019s pain inhibitory network","volume":"8","author":"Jensen","year":"2012","journal-title":"Mol. Pain"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/1756-185X.12550","article-title":"Some oxidative and antioxidative parameters and their relationship with clinical symptoms in women with fibromyalgia syndrome","volume":"20","author":"Fatima","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_54","first-page":"S128","article-title":"Oxidative stress and antioxidative parameters and metal ion content in patients with fibromyalgia syndrome: Implications in the pathogenesis of the disease","volume":"31","author":"Fatima","year":"2013","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_55","first-page":"S121","article-title":"Is fibromyalgia-related oxidative stress implicated in the decline of physical and mental health status","volume":"31","author":"Rus","year":"2013","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1517\/14728222.2013.818657","article-title":"The role of mitochondrial dysfunctions due to oxidative and nitrosative stress in the chronic pain or chronic fatigue syndromes and fibromyalgia patients: Peripheral and central mechanisms as therapeutic targets?","volume":"17","author":"Meeus","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_57","first-page":"166","article-title":"Mast cells","volume":"63","author":"Saito","year":"2005","journal-title":"Nihon Rinsho"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.jaip.2013.09.004","article-title":"The Mastocytosis Society survey on mast cell disorders: Patient experiences and perceptions","volume":"2","author":"Jennings","year":"2014","journal-title":"J. Allergy Clin. Immunol. Pract."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1056\/NEJMra1409760","article-title":"Mast Cells, Mastocytosis, and Related Disorders","volume":"373","author":"Theoharides","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"353","DOI":"10.3389\/fncel.2019.00353","article-title":"Mast Cells, Neuroinflammation and Pain in Fibromyalgia Syndrome","volume":"13","author":"Theoharides","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1177\/205873920601900102","article-title":"Fibromyalgia\u2014New concepts of pathogenesis and treatment","volume":"19","author":"Lucas","year":"2006","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_62","first-page":"S140","article-title":"Mast cells in fibromyalgia","volume":"33","author":"Pollack","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1016\/j.clinthera.2013.04.002","article-title":"Atopic conditions in search of pathogenesis and therapy","volume":"35","author":"Theoharides","year":"2013","journal-title":"Clin. Ther."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1177\/1073858416687249","article-title":"Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons","volume":"23","author":"Skaper","year":"2017","journal-title":"Neuroscientist"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jneuroim.2013.09.018","article-title":"A focus on mast cells and pain","volume":"264","author":"Heron","year":"2013","journal-title":"J. Neuroimmunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.molimm.2014.03.001","article-title":"Mast cells: Versatile gatekeepers of pain","volume":"63","author":"Chatterjea","year":"2015","journal-title":"Mol. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"29069","DOI":"10.3390\/ijms161226151","article-title":"Mast Cell-Mediated Mechanisms of Nociception","volume":"16","author":"Aich","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/0006-8993(76)90356-5","article-title":"Autonomic nerves, mast cells, and amine receptors in human brain vessels. A histochemical and pharmacological study","volume":"115","author":"Edvinsson","year":"1976","journal-title":"Brain Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/0165-3806(90)90077-C","article-title":"Migration of mast cells in the developing rat brain","volume":"56","author":"Dimitriadou","year":"1990","journal-title":"Brain Res. Dev. Brain Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jdermsci.2007.09.009","article-title":"Mast cells: Versatile regulators of inflammation, tissue remodeling, host defense and homeostasis","volume":"49","author":"Galli","year":"2008","journal-title":"J. Dermatol. Sci."},{"key":"ref_71","first-page":"293","article-title":"Brain IL-1beta was involved in reserpine-induced behavioral depression in rats","volume":"25","author":"Huang","year":"2004","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1111\/j.1749-6632.2000.tb05378.x","article-title":"Contribution of differently localized alpha (2)- and beta-adrenoceptors in the modulation of TNF-alpha and IL-10 production in endotoxemic","volume":"917","author":"Szelenyi","year":"2000","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/j.neuron.2017.08.020","article-title":"Synapse-Specific Encoding of Fear Memory in the Amygdala","volume":"95","author":"Maren","year":"2017","journal-title":"Neuron"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.4049\/jimmunol.172.2.1227","article-title":"Prostaglandin E-2 induces degranulation-independent production of vascular endothelial growth factor by human mast cells","volume":"172","author":"Marshall","year":"2004","journal-title":"J. Immunol."},{"key":"ref_75","first-page":"1564","article-title":"Role of reactive oxygen species in mast cell degranulation","volume":"81","author":"Chelombitko","year":"2016","journal-title":"Biochemistry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"349","DOI":"10.2165\/0063030-200822060-00002","article-title":"Targeting Nerve Growth Factor in Pain What is the Therapeutic Potential","volume":"22","author":"Watson","year":"2008","journal-title":"Biodrugs"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1853","DOI":"10.1182\/blood-2013-04-498105","article-title":"Mast cell activation contributes to sickle cell pathobiology and pain in mice","volume":"122","author":"Vincent","year":"2013","journal-title":"Blood"},{"key":"ref_78","first-page":"598","article-title":"Mast cell degranulation activates a pain pathway underlying migraine headache","volume":"27","author":"Kainz","year":"2007","journal-title":"Cephalalgia"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pain.2004.12.002","article-title":"Unilateral spinal nerve ligation leads to an asymmetrical distribution of mast cells in the thalamus of female but not male mice","volume":"114","author":"Taiwo","year":"2005","journal-title":"Pain"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.1096\/fj.11-197194","article-title":"Microglia and mast cells: Two tracks on the road to neuroinflammation","volume":"26","author":"Skaper","year":"2012","journal-title":"Faseb J."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.2174\/1871527313666141130224206","article-title":"Neuroinflammation, Microglia and Mast Cells in the Pathophysiology of Neurocognitive Disorders: A Review","volume":"13","author":"Skaper","year":"2014","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1016\/S0928-4257(02)00018-9","article-title":"Brain plasticity and microglia: Is transsynaptic glial activation in the thalamus after limb denervation linked to cortical plasticity and central sensitisation?","volume":"96","author":"Banati","year":"2002","journal-title":"J. Physiol. Paris"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.sjpain.2010.01.002","article-title":"Long-term pain, neuroinflammation and glial activation","volume":"1","author":"Hansson","year":"2010","journal-title":"Scand. J. 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