The protective effect of modafinil on vincristine-induced peripheral neuropathy in rats: A possible role for TRPA1 receptors
The protective effect of modafinil on vincristine-induced peripheral neuropathy in rats: A possible role for TRPA1 receptors
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DOI：
10.1111/bcpt.13454
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发表时间：
2020-07-03
影响因子：
3.1
通讯作者：
Dehpour, Ahmad Reza
中科院分区：
文献类型：
--
作者：
Amirkhanloo, Fatemeh;Karimi, Gholamreza;Dehpour, Ahmad Reza
长春新碱(VCR)可引起周围神经病变。我们的目的是评估莫达非尼对长春新碱所致大鼠神经病变的疗效。用腹腔注射(Ip)诱发神经病变。注射长春新碱(0.1 mg/kg)。神经病变组给予莫达非尼(5、25和50 mg/kg)、加巴喷丁(20 mg/kg)以及莫达非尼(5和50 mg/kg)和加巴喷丁(20 mg/kg)的组合。然后进行电生理、行为学、生化和病理学评价。甩尾潜伏期、von Frey细丝潜伏期、运动神经传导速度(MNCV)及神经传导兴奋时间缩短。此外，瞬时受体电位阳离子通道锚蛋白1(TRPA1)水平升高，而TRPV1和N-甲基-D-天冬氨酸(NMDA)水平不变。肿瘤坏死因子-α(TNF-α)和白介素1-β(IL-1β)水平明显升高。莫达非尼的预治疗通过延长潜伏期、MNCV和兴奋性，降低TRPA1、TNF-α和IL-1β水平来预防感觉运动神经病。莫达非尼可改善行为、电生理和病理障碍。结果表明，在VCR诱导的神经病理性疼痛中，TRPA1比NMDA和TRPV1具有更重要的作用。此外，炎性介质--肿瘤坏死因子-α和白介素1-β也参与其中。此外，莫达非尼和加巴喷丁的联合使用改善了加巴喷丁的神经保护作用。因此，莫达非尼可能是一种预防VCR所致神经病变的神经保护剂。
Vincristine (VCR) induces peripheral neuropathy. We aimed to assess the efficacy of modafinil on VCR-induced neuropathy in rats. Neuropathy was induced by intraperitoneal (i.p.) injections of VCR (0.1 mg/kg). Neuropathic groups received modafinil (5, 25 and 50 mg/kg); gabapentin (20 mg/kg); and a combination of modafinil (5 and 50 mg/kg) and gabapentin (20 mg/kg,). Then, electrophysiological, behavioural, biochemical and pathological evaluations were performed. Latencies of tail-flick and von Frey filament tests, motor nerve conduction velocity (MNCV) and excitation of nerve conduction were decreased. Moreover, the transient receptor potential cation channel ankyrin 1 (TRPA1) level was increased, while TRPV1 and N-Methyl-D-aspartate (NMDA) levels remained unchanged. Tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1 beta) levels were markedly elevated. Pre-treatment with modafinil prevented sensorimotor neuropathy by raising latencies, MNCV and excitation, reducing TRPA1, TNF-alpha and IL-1 beta levels. Modafinil improved behavioural, electrophysiological and pathological disturbances. The results showed that TRPA1 has a more important role than NMDA and TRPV1, in VCR-induced neuropathic pain. In addition, inflammatory mediators, TNF-alpha and IL-1 beta, were involved. Further, the combination of modafinil and gabapentin improved the neuroprotective effect of gabapentin. So, modafinil might be a neuroprotective agent in the prevention of VCR-induced neuropathy.