Taiji Ryo, Yamanaka Manabu, Taniguchi Wataru, Nishio Naoko, Tsutsui Shunji, Nakatsuka Terumasa, Yamada Hiroshi
Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.
Pain Research Center, Kansai University of Health Sciences, 2-11-1 Wakaba, Kumatori, Osaka, 590-0482, Japan.
Biochem Biophys Rep. 2021 Sep 10;28:101130. doi: 10.1016/j.bbrep.2021.101130. eCollection 2021 Dec.
Riluzole (2-amino-6-(trifluoromethoxy)benzothiazole) is a drug known for its inhibitory effect on glutamatergic transmission and its anti-nociceptive and anti-allodynic effects in neuropathic pain rat models. Riluzole also has an enhancing effect on GABAergic synaptic transmission. However, the effect on the spinal dorsal horn, which plays an important role in modulating nociceptive transmission, remains unknown. We investigated the ameliorating effect of riluzole on mechanical allodynia using the von Frey test in a rat model of neuropathic pain and analyzed the synaptic action of riluzole on inhibitory synaptic transmission in substantia gelatinosa (SG) neurons using whole-cell patch clamp recordings. We found that single-dose intraperitoneal riluzole (4 mg/kg) administration effectively attenuated mechanical allodynia in the short term in a rat model of neuropathic pain. Moreover, 300 μM riluzole induced an outward current in rat SG neurons. The outward current induced by riluzole was not suppressed in the presence of tetrodotoxin. Furthermore, we found that the outward current was suppressed by simultaneous bicuculline and strychnine application, but not by strychnine alone. Altogether, these results suggest that riluzole enhances inhibitory synaptic transmission monosynaptically by potentiating GABAergic synaptic transmission in the rat spinal dorsal horn.
利鲁唑（2-氨基-6-（三氟甲氧基）苯并噻唑）是一种药物，因其对谷氨酸能传递的抑制作用以及在神经性疼痛大鼠模型中的抗伤害感受和抗异常性疼痛作用而闻名。利鲁唑对γ-氨基丁酸能（GABAergic）突触传递也有增强作用。然而，其对在调节伤害性传递中起重要作用的脊髓背角的影响尚不清楚。我们使用von Frey试验在神经性疼痛大鼠模型中研究了利鲁唑对机械性异常性疼痛的改善作用，并使用全细胞膜片钳记录分析了利鲁唑对脊髓背角胶状质（SG）神经元抑制性突触传递的突触作用。我们发现，在神经性疼痛大鼠模型中，单剂量腹腔注射利鲁唑（4mg/kg）在短期内有效减轻了机械性异常性疼痛。此外，300μM利鲁唑在大鼠SG神经元中诱导出外向电流。利鲁唑诱导的外向电流在存在河豚毒素的情况下未被抑制。此外，我们发现，同时应用荷包牡丹碱和士的宁可抑制外向电流，但单独使用士的宁则不能。总之，这些结果表明，利鲁唑通过增强大鼠脊髓背角的GABA能突触传递来单突触地增强抑制性突触传递。
