Xiao Zhang,1,* Yandong Gao,2,* Qun Wang,1 Shibin Du,1 Xiaolan He,1 Nan Gu,1 Yan Lu1 1Department of Pain Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China; 2Department of Anesthesiology, First Hospital of Yulin City, Yulin 719000, China *These authors contributed equally to this work Purpose: Riluzole – a major therapeutic medicine for patients with amyotrophic lateral sclerosis – reportedly has anti-nociceptive and anti-allodynic efficacies in neuropathic pain

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... dels. 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. Materials and methods: 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. Results: 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 postsynaptic GluR2 contributes to the riluzole-induced long-term depression (LTD) of the spinal nociceptive pathway. Conclusion: 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. Keywords: riluzole, neuropathic pain, superficial dorsal horn, SSDH, long-term depression, LTD, AMPA receptor endocytosis