Central neuropathic pain is a common untreated symptom in progressive multiple sclerosis (PMS) and is associated with poor quality of life and interference with patients' daily activities. The neuroinflammation process and mitochondrial dysfunction in the PMS lesions generate reactive species. The transient potential receptor ankyrin 1 (TRPA1) has been identified as one of the major mechanisms that contribute to neuropathic pain signaling and can be activated by reactive compounds. Thus, the goal of our study was to evaluate the role of spinal TRPA1 in the central neuropathic pain observed in a PMS model in mice. We used C57BL/6 female mice (20-30 g), and the PMS model was induced by the experimental autoimmune encephalomyelitis (EAE) using mouse myelin oligodendrocyte glycoprotein (MOG35-55) antigen and CFA (complete Freund's adjuvant). Mice developed progressive clinical score, with motor impairment observed after 15 days of induction. This model induced mechanical and cold allodynia and heat hyperalgesia which were measured up to 14 days after induction. The hypersensitivity observed was reduced by the administration of selective TRPA1 antagonists (HC-030031 and A-967079, via intrathecal and intragastric), antioxidants (α-lipoic acid and apocynin, via intrathecal and intragastric), and TRPA1 antisense oligonucleotide (via intrathecal). We also observed an increase in TRPA1 mRNA levels, NADPH oxidase activity, and 4-hydroxinonenal (a TRPA1 agonist) levels in spinal cord samples of PMS-EAE induced animals. In conclusion, these results support the hypothesis of the TRPA1 receptor involvement in nociception observed in a PMS-EAE model in mice.

中文翻译：

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小鼠进行性多发性硬化模型中的伤害感受依赖于脊髓 TRPA1 通道的激活。

中枢神经性疼痛是进行性多发性硬化症 (PMS) 中常见的未经治疗的症状，与生活质量差和患者日常活动的干扰有关。PMS 病变中的神经炎症过程和线粒体功能障碍会产生反应性物质。瞬时电位受体锚蛋白 1 (TRPA1) 已被确定为导致神经性疼痛信号传导的主要机制之一，并且可以被反应性化合物激活。因此，我们研究的目的是评估脊髓 TRPA1 在小鼠 PMS 模型中观察到的中枢神经性疼痛中的作用。我们使用 C57BL/6 雌性小鼠 (20-30 g)，并使用小鼠髓鞘少突胶质细胞糖蛋白 (MOG35-55) 抗原和 CFA (完全弗氏佐剂) 通过实验性自身免疫性脑脊髓炎 (EAE) 诱导 PMS 模型。小鼠出现渐进的临床评分，在诱导 15 天后观察到运动障碍。该模型诱导了机械性和冷性异常性疼痛以及热痛觉过敏，在诱导后长达 14 天进行了测量。通过使用选择性 TRPA1 拮抗剂（HC-030031 和 A-967079，通过鞘内和胃内）、抗氧化剂（α-硫辛酸和夹竹桃麻素，通过鞘内和胃内）和 TRPA1 反义寡核苷酸（通过鞘内），观察到的超敏反应降低了. 我们还观察到 PMS-EAE 诱导的动物脊髓样本中 TRPA1 mRNA 水平、NADPH 氧化酶活性和 4-羟基辛酮（一种 TRPA1 激动剂）水平的增加。总之，这些结果支持在小鼠 PMS-EAE 模型中观察到的 TRPA1 受体参与伤害感受的假设。