Central neuropathic pain is the main symptom caused by spinal cord lesion in relapsing-remitting multiple sclerosis (RRMS), but its management is still not effective. The transient receptor potential ankyrin 1 (TRPA1) is a pain detecting ion channel involved in neuropathic pain development. Thus, the aim of our study was to evaluate the role of TRPA1 in central neuropathic nociception induced by relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) mouse model. In this model, we observed the development of similar clinical conditions of RRMS in C57BL/6 female mice through RR-EAE using MOG35-55 antigen and Quil A adjuvant. At the thirty-fifth day post-induction, C57BL/6 female mice demonstrated alteration in the RR-EAE score without motor impairment, mechanical and cold allodynia. Also, significative changes in demyelinating (Mog and olig-1) and neuroinflammatory (Iba1, Gfap and Tnfa) markers were observed, but this model did not alter Trpa1 RNA expression levels in the spinal cord. The hydrogen peroxide and 4-hydroxynonenal levels (TRPA1 agonists) were increased in RR-EAE induced mice, as well as the NADPH oxidase activity. The intragastric treatment of RR-EAE induced mice with TRPA1 antagonists (HC-030031 and A-967079) and antioxidant (α-lipoic acid and apocynin) caused an antiallodynic effect. Moreover, the intrathecal administration of TRPA1 antisense oligonucleotide, HC-030031, α-lipoic acid, and apocynin transiently attenuated mechanical and cold allodynia. Thus, TRPA1 plays a key role in the induction of neuropathic pain in this model of RR-EAE and can be a possible target for investigating the development of pain in RRMS patients.

中文翻译：

---

TRPA1激活介导复发-释放实验性自身免疫性脑脊髓炎的小鼠模型中的伤害感受行为。

中枢神经性疼痛是复发性多发性硬化症（RRMS）中由脊髓病变引起的主要症状，但其管理仍无效。瞬时受体电位锚蛋白1（TRPA1）是涉及神经性疼痛发展的疼痛检测离子通道。因此，我们的研究目的是评估TRPA1在复发缓解型实验性自身免疫性脑脊髓炎（RR-EAE）小鼠模型诱导的中枢神经性伤害感受中的作用。在此模型中，我们观察到使用MOG35-55抗原和Quil A佐剂通过RR-EAE在C57BL / 6雌性小鼠中产生RRMS的类似临床状况。诱导后第三十五天，C57BL / 6雌性小鼠表现出RR-EAE评分的改变，而没有运动障碍，机械性和冷性异常性疼痛。也，观察到脱髓鞘（Mog和olig-1）和神经炎症（Iba1，Gfap和Tnfa）标志物发生了显着变化，但该模型并未改变脊髓中Trpa1 RNA的表达水平。RR-EAE诱导的小鼠中过氧化氢和4-羟基壬烯醛水平（TRPA1激动剂）以及NADPH氧化酶活性均升高。用TRPA1拮抗剂（HC-030031和A-967079）和抗氧化剂（α-硫辛酸和载脂蛋白）对RR-EAE诱导的小鼠进行胃内治疗可产生抗痛觉过敏作用。此外，鞘内注射TRPA1反义寡核苷酸，HC-030031，α-硫辛酸和载脂蛋白具有暂时性减弱机械和冷异常性疼痛的作用。从而，