Laboratory of Pain and Signaling, Butantan Institute, Sao Paulo 05503-900, SP, Brazil.
Department of Pathological Sciences, Medical Science School Santa Casa of Sao Paulo, Sao Paulo 01221-020, SP, Brazil.
Toxins (Basel). 2021 Nov 22;13(11):827. doi: 10.3390/toxins13110827.
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 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-α 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.
多发性硬化症（MS）是一种炎症性和自身免疫性脱髓鞘疾病，可导致感觉和进行性运动障碍，包括疼痛。免疫系统的细胞通过诱导神经炎症、组织损伤和脱髓鞘积极参与 MS 的发病机制和进展。Crotoxin（CRO）是在蛇毒液中首次鉴定出的肽的结构类似物，通过内源性阿片类物质释放和 2 型大麻素受体（CB2）激活来诱导镇痛。由于 CB2 的激活可下调神经炎症并改善 MS 小鼠模型的症状，因此目前研究了 CRO 是否对实验性自身免疫性脑脊髓炎（EAE）有有益作用。CRO 在免疫后第 5 天单次给药或在疾病高峰期开始的 5 次剂量中给药。CRO 部分逆转了 EAE 引起的机械性痛觉过敏，并降低了临床症状的严重程度。此外，CRO 减少了脊髓中的炎症浸润和小胶质细胞激活，随后下调 TNF-α 和 IL-17。在外周，CRO 恢复了 EAE 引起的坐骨神经髓鞘厚度的损伤。因此，CRO 干扰了中枢和外周神经炎症，为 MS 的控制开辟了前景。
