Riluzole induces LTD of spinal nociceptive signaling via postsynaptic GluR2 receptors.
Riluzole induces LTD of spinal nociceptive signaling via postsynaptic GluR2 receptors.
复制标题
利鲁唑通过突触后 GluR2 受体诱导脊髓伤害性信号传导的 LTD
DOI：
10.2147/jpr.s169686
复制
发表时间：
2018
影响因子：
2.7
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Zhang X;Gao Y;Wang Q;Du S;He X;Gu N;Lu Y
利鲁唑是肌萎缩性侧索硬化症患者的主要治疗药物，据报道，它在神经性疼痛模型中具有抗伤害性和抗变动力的功效。然而，其对脊髓浅背角（SDH）神经传递的影响尚不清楚。本研究旨在探讨利鲁唑在生理和病理条件下对SDH痛觉通路突触传递的影响。采用脊髓神经结扎法建立神经性疼痛模型。用Von Frey纤维评估机械异常性痛行为。采用膜片钳法观察利鲁唑在生理和病理条件下对大鼠SDH神经元伤害性突触传递的影响。本研究的主要发现有三个方面。首先，我们证实利鲁唑对体内和体外病理疼痛模型都有显著的长效镇痛作用。其次，利鲁唑对脊髓痛觉信号的长期抑制作用是由突触前和突触后机制介导的。最后，突触后GluR2的内吞作用有助于利鲁唑诱导的脊髓伤害感受通路的长期抑制（LTD）。本研究发现，利鲁唑通过与GluR2内吞作用相关的突触后AMPA受体，诱导SDH中伤害性信号通路的有限，并在神经损伤引起的神经性疼痛中产生持久的抗异痛觉作用。
Riluzole – a major therapeutic medicine for patients with amyotrophic lateral sclerosis – reportedly has anti-nociceptive and anti-allodynic efficacies in neuropathic pain models. However, little is known about its effect on neurotransmission in the spinal superficial dorsal horn (SDH). The present study aims to investigate the effects of riluzole on the synaptic transmission of SDH nociceptive pathways in both physiological and pathological conditions. Spinal nerve ligation was used to produce a neuropathic pain model. Mechanical allodynia behavior was assessed with Von Frey filaments. Riluzole’s effects on nociceptive synaptic transmission under both physiological and pathological conditions were examined by patch-clamp recordings in rat SDH neurons. The principal findings of the present study are three-fold. First, we affirm that riluzole has a remarkable long-lasting analgesic effect on both in vitro and in vivo pathological pain models. Second, the prolonged inhibitory effects of riluzole on spinal nociceptive signaling are mediated by both presynaptic and postsynaptic mechanisms. Finally, endocytosis of post-synaptic GluR2 contributes to the riluzole-induced long-term depression (LTD) of the spinal nociceptive pathway. The present study finds that riluzole induces LTD of nociceptive signaling in the SDH and produces long-lasting anti-allodynia effects in nerve injury-induced neuropathic pain conditions via postsynaptic AMPA receptors associated with the endocytosis of GluR2.