{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:23:19Z","timestamp":1791663799462,"version":"4.3.4"},"reference-count":103,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,22]],"date-time":"2021-11-22T00:00:00Z","timestamp":1637539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"National Council for Scientific and Technological Development","doi-asserted-by":"publisher","award":["467211\/2014-0"],"award-info":[{"award-number":["467211\/2014-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Finance Code 001"],"award-info":[{"award-number":["Finance Code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["Cetics program 2013\/07467-1"],"award-info":[{"award-number":["Cetics program 2013\/07467-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2015\/01254-1"],"award-info":[{"award-number":["2015\/01254-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Multiple sclerosis (MS) is a demyelinating disease of inflammatory and autoimmune origin, which induces sensory and progressive motor impairments, including pain. Cells of the immune system actively participate in the pathogenesis and progression of MS by inducing neuroinflammation, tissue damage, and demyelination. Crotalphine (CRO), a structural analogue to a peptide firstly identified in Crotalus durissus terrificus snake venom, induces analgesia by endogenous opioid release and type 2 cannabinoid receptor (CB2) activation. Since CB2 activation downregulates neuroinflammation and ameliorates symptoms in mice models of MS, it was presently investigated whether CRO has a beneficial effect in the experimental autoimmune encephalomyelitis (EAE). CRO was administered on the 5th day after immunization, in a single dose, or five doses starting at the peak of disease. CRO partially reverted EAE-induced mechanical hyperalgesia and decreased the severity of the clinical signs. In addition, CRO decreases the inflammatory infiltrate and glial cells activation followed by TNF-\u03b1 and IL-17 downregulation in the spinal cord. Peripherally, CRO recovers the EAE-induced impairment in myelin thickness in the sciatic nerve. Therefore, CRO interferes with central and peripheral neuroinflammation, opening perspectives to MS control.<\/jats:p>","DOI":"10.3390\/toxins13110827","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T03:12:40Z","timestamp":1638328360000},"page":"827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Crotalphine Attenuates Pain and Neuroinflammation Induced by Experimental Autoimmune Encephalomyelitis in Mice"],"prefix":"10.3390","volume":"13","author":[{"given":"Aline C.","family":"Giardini","sequence":"first","affiliation":[{"name":"Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca G.","family":"Evangelista","sequence":"additional","affiliation":[{"name":"Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2682-3860","authenticated-orcid":false,"given":"Morena B.","family":"Sant\u2019Anna","sequence":"additional","affiliation":[{"name":"Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara B.","family":"Martins","sequence":"additional","affiliation":[{"name":"Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen L. P.","family":"Lancellotti","sequence":"additional","affiliation":[{"name":"Department of Pathological Sciences, Medical Science School Santa Casa of Sao Paulo, Sao Paulo 01221-020, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2912-3376","authenticated-orcid":false,"given":"Adriano P.","family":"Ciena","sequence":"additional","affiliation":[{"name":"Laboratory of Morphology, Institute of Biosciences, S\u00e3o Paulo State University, Rio Claro 13506-52, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marucia","family":"Chacur","sequence":"additional","affiliation":[{"name":"Laboratory of Functional Neuroanatomy of Pain, Instituto de Ci\u00eancias Biom\u00e9dicas, Universidade de Sao Paulo, Sao Paulo 05508-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5351-6575","authenticated-orcid":false,"given":"Rosana L.","family":"Pagano","sequence":"additional","affiliation":[{"name":"Laboratory of Neuroscience, Hospital S\u00edrio-Liban\u00eas, Sao Paulo 01308-060, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2117-2402","authenticated-orcid":false,"given":"Orlando G.","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Laboratory of Immunogenetics, Butantan Institute, Sao Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0890-9561","authenticated-orcid":false,"given":"Vanessa O.","family":"Zambelli","sequence":"additional","affiliation":[{"name":"Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6784-8266","authenticated-orcid":false,"given":"Gisele","family":"Picolo","sequence":"additional","affiliation":[{"name":"Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo 05503-900, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,22]]},"reference":[{"key":"ref_1","unstructured":"The Multiple Sclerosis International Federation Atlas of MS: Mapping Multiple Sclerosis Around of World, The Multiple Sclerosis International Federation. 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