Anti-allodynic and promotive effect on inhibitory synaptic transmission of riluzole in rat spinal dorsal horn

Ryo Taiji; Manabu Yamanaka; Wataru Taniguchi; Naoko Nishio; Shunji Tsutsui; Terumasa Nakatsuka; Hiroshi Yamada

doi:10.1016/j.bbrep.2021.101130

Anti-allodynic and promotive effect on inhibitory synaptic transmission of riluzole in rat spinal dorsal horn

Biochem Biophys Rep. 2021 Sep 10:28:101130. doi: 10.1016/j.bbrep.2021.101130. eCollection 2021 Dec.

Authors

Ryo Taiji¹, Manabu Yamanaka¹, Wataru Taniguchi¹, Naoko Nishio¹, Shunji Tsutsui¹, Terumasa Nakatsuka², Hiroshi Yamada¹

Affiliations

¹ Department of Orthopaedic Surgery, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-8510, Japan.
² Pain Research Center, Kansai University of Health Sciences, 2-11-1 Wakaba, Kumatori, Osaka, 590-0482, Japan.

Abstract

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.

Keywords: CCI, chronic constriction injury; IPSC, inhibitory postsynaptic current; Mechanical allodynia; Neuropathic pain; Nociceptive transmission; Riluzole; SG, substantia gelatinosa; SNI, spared nerve injury; Spinal dorsal horn; TTX, tetrodotoxin.