دورية أكاديمية
أعرض في EDS

Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG 35-55 -induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.

التفاصيل البيبلوغرافية
العنوان: Crotoxin down-modulates pro-inflammatory cells and alleviates pain on the MOG 35-55 -induced experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.
المؤلفون: Teixeira NB; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil., Sant'Anna MB; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil., Giardini AC; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil., Araujo LP; Department of Microbiology, Immunology and Parasitology, Paulista School of Medicine, Federal University of Sao Paulo, UNIFESP, Sao Paulo, Brazil., Fonseca LA; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil., Basso AS; Department of Microbiology, Immunology and Parasitology, Paulista School of Medicine, Federal University of Sao Paulo, UNIFESP, Sao Paulo, Brazil., Cury Y; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil., Picolo G; Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo, Brazil. Electronic address: gisele.picolo@butantan.gov.br.
المصدر: Brain, behavior, and immunity [Brain Behav Immun] 2020 Feb; Vol. 84, pp. 253-268. Date of Electronic Publication: 2019 Dec 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 8800478 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2139 (Electronic) Linking ISSN: 08891591 NLM ISO Abbreviation: Brain Behav Immun Subsets: MEDLINE
أسماء مطبوعة: Publication: <2000- > : Amsterdam : Elsevier
Original Publication: San Diego : Academic Press, [c1987-
مواضيع طبية MeSH: Crotoxin*/pharmacology , Crotoxin*/therapeutic use , Encephalomyelitis, Autoimmune, Experimental*/drug therapy , Multiple Sclerosis*/complications , Multiple Sclerosis*/drug therapy , Pain*/drug therapy , Pain*/etiology, Animals ; Anti-Inflammatory Agents/pharmacology ; Anti-Inflammatory Agents/therapeutic use ; Disease Models, Animal ; Female ; Humans ; Mice ; Mice, Inbred C57BL
مستخلص: Multiple sclerosis (MS) is a Central Nervous System inflammatory demyelinating disease that has as primary symptoms losses of sensory and motor functions, including chronic pain. To date, however, few studies have investigated the mechanisms of chronic pain in animal models of MS since locomotor impairments render difficult its evaluation. It was previously demonstrated that in the MOG 35-55 -induced EAE, an animal model of MS, the hypernociception appears before the onset of motor disability, allowing for the study of these two phenomena separately. Here, we evaluated the effect of crotoxin (CTX), a neurotoxin isolated from the Crotalus durissus terrificus snake venom that displays, at non-toxic dose, antinociceptive, anti-inflammatory and immunomodulatory effects, in the pain and in symptoms progression of EAE. The pain threshold of female C57BL/6 mice decreased at the 4th day after immunization, while the first sign of disease appeared around the 11st-12nd days, coinciding with the onset of motor abnormalities. CTX (40 µg/kg, s.c.) administered in a single dose on the 5th day after immunization, induced a long-lasting analgesic effect (5 days), without interfering with the clinical signs of the disease. On the other hand, when crotoxin was administered for 5 consecutive days, from 5th-9th day after immunization, it induced analgesia and also reduced EAE progression. The antinociceptive effect of crotoxin was blocked by Boc-2 (0.5 mg/kg, i.p.), a selective antagonist of formyl peptide receptors, by NDGA (30 μg/kg, i.p.), a lipoxygenase inhibitor and by atropine sulfate (10 mg/kg, i.p.), an antagonist of muscarinic receptors, administered 30 min before CTX. CTX was also effective in decreasing EAE clinical signs even when administered after its onset. Regarding the interactions between neurons and immunocompetent cells, CTX, in vitro, was able to reduce T cell proliferation, decreasing Th1 and Th17 and increasing Treg cell differentiation. Furthermore, in EAE model, the treatment with 5 consecutive doses of CTX inhibited IFN-γ-producing T cells, GM-CSF-producing T cells, reduced the frequency of activated microglia/macrophages within the CNS and decreased the number of migrating cell to spinal cord and cerebellum at the peak of the disease. These results suggest that CTX is a potential treatment not only for pain alteration but also for clinical progression induced by the disease as well as an useful tool for the development of new therapeutic approaches for the multiple sclerosis control.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
فهرسة مساهمة: Keywords: Analgesia; Crotoxin; Experimental autoimmune encephalomyelitis; Immunomodulatory effect; Multiple sclerosis
المشرفين على المادة: 0 (Anti-Inflammatory Agents)
9007-40-3 (Crotoxin)
تواريخ الأحداث: Date Created: 20191218 Date Completed: 20210309 Latest Revision: 20210309
رمز التحديث: 20221213
DOI: 10.1016/j.bbi.2019.12.009
PMID: 31843645
قاعدة البيانات: MEDLINE
الوصف
تدمد:1090-2139
DOI:10.1016/j.bbi.2019.12.009