Stiripentol alleviates neuropathic pain in L5 spinal nerve-transected mice
Stiripentol alleviates neuropathic pain in L5 spinal nerve-transected mice
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DOI：
10.1007/s00540-020-02762-2
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发表时间：
2020-03-18
影响因子：
2.8
通讯作者：
Minami, Toshiaki
中科院分区：
文献类型：
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作者：
Fujiwara, Atsushi;Nakao, Kenta;Minami, Toshiaki
目的抗癫痫药物不仅用于癫痫的治疗，也用于神经性疼痛的治疗。然而，它们的作用机制并不总是得到很好的解释。斯立戊醇是一种有效的抗癫痫药物，最近被证明可以作为星形胶质细胞乳酸脱氢酶的抑制剂。在本研究中，我们研究了施曲妥醇对L5脊髓神经横断小鼠神经性疼痛的影响。方法对L5脊髓神经横断小鼠鞘内给药后，采用标定的von Frey纤维和星形胶质细胞标记物胶质纤维酸性蛋白的免疫组化进行行为学测试。结果与加巴喷丁、卡马西平等抗惊厥药一样，在L5脊神经横断后7、14和28天，施替利妥醇能以剂量依赖性的方式减轻L5脊神经横断引起的机械性痛痛过敏。同样，α -氰基-4-羟基肉桂酸，一种广泛的单羧酸转运蛋白抑制剂，可以减轻L5脊神经横断引起的机械性痛觉过敏。同时给药l-乳酸可抑制施力哌醇、卡马西平和-氰基-4-羟基肉桂酸引起的镇痛作用，而加巴喷丁没有。抗惊厥药均不影响胶质原纤维酸性蛋白的免疫反应性。结论本研究表明，施曲妥醇对神经性疼痛有一定的治疗作用，并提示星形胶质细胞-乳酸神经元穿梭与神经性疼痛有关。
Purpose Antiepileptic drugs are used not only for the treatment of epilepsy but also for that of neuropathic pain. However, their action mechanisms have not always been well explained. Stiripentol, an effective antiepileptic drug indicated as a therapeutic for Dravet syndrome, was recently shown to act as an inhibitor of lactate dehydrogenase in astrocytes. In this present study, we examined the effect of stiripentol on neuropathic pain in L5 spinal nerve-transected mice. Methods We carried out behavioral tests using calibrated von Frey filaments and the immunohistochemistry of glial fibrillary acidic protein, an astrocyte marker, in L5 spinal nerve-transected mice after intrathecal administration of drugs. Results Like other anticonvulsants such as gabapentin and carbamazepine, stiripentol alleviated mechanical hyperalgesia induced by L5 spinal nerve transection in a dose-dependent manner, when intrathecally administered to mice 7, 14, and 28 days after L5 spinal nerve transection. Likewise, alpha-cyano-4-hydroxycinnamic acid, a broad inhibitor of monocarboxylate transporters, diminished mechanical hyperalgesia induced by L5 spinal nerve transection. Simultaneous administration of l-lactate negated the analgesic effect elicited by stiripentol, carbamazepine or alpha-cyano-4-hydroxycinnamic acid, but not that by gabapentin. None of the anticonvulsants affected the immunoreactivity of glial fibrillary acidic protein. Conclusions This present study demonstrated that stiripentol was effective against neuropathic pain and suggested that the astrocyte-neuron lactate shuttle was involved in such pain.