Zhang Xiao, Gao Yandong, Wang Qun, Du Shibin, He Xiaolan, Gu Nan, Lu Yan
Department of Pain Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China,
Department of Anesthesiology, First Hospital of Yulin City, Yulin 719000, China.
J Pain Res. 2018 Oct 26;11:2577-2586. doi: 10.2147/JPR.S169686. eCollection 2018.
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.
利鲁唑是肌萎缩侧索硬化症患者的主要治疗药物，据报道在神经病理性疼痛模型中具有抗伤害感受和抗痛觉过敏的功效。然而，其对脊髓浅表背角（SDH）神经传递的影响却鲜为人知。本研究旨在探究利鲁唑在生理和病理条件下对SDH伤害性感受通路突触传递的影响。
采用脊髓神经结扎术建立神经病理性疼痛模型。用von Frey细丝评估机械性痛觉过敏行为。通过对大鼠SDH神经元进行膜片钳记录，研究利鲁唑在生理和病理条件下对伤害性突触传递的影响。
本研究的主要发现有三点。第一，我们证实利鲁唑对体外和体内病理疼痛模型均有显著的长效镇痛作用。第二，利鲁唑对脊髓伤害性信号的延长抑制作用是由突触前和突触后机制介导的。最后，突触后GluR2的内吞作用促成了利鲁唑诱导的脊髓伤害性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中伤害性信号的LTD，并在神经损伤诱导的神经病理性疼痛状态下产生长效抗痛觉过敏作用。
