Analgesic characteristics of a newly developed α2δ ligand, mirogabalin, on inflammatory pain. (26th November 2021)

• Record Type: Journal Article
• Authors: Komatsu, Shuji; Nakamura, Shingo; Nonaka, Takahiro; Yamada, Toshihiko; Yamamoto, Tatsuo
• Is Part Of: Molecular pain. Volume 17(2021)
• Publication Date: 2021-11-26
• Subjects: Mirogabalin -- formalin test -- open field test -- gabapentinoid -- analgesics; Pain -- Molecular aspects -- Periodicals; Pain -- Pathophysiology -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1177/17448069211052167
• Languages: English
• ISSNs: 1744-8069

Abstract

Mirogabalin is a novel α2 δ ligand approved in Japan for the treatment of peripheral neuropathic pain. However, the sites of action of α2 δ ligands to produce analgesic effects on inflammatory pain remain unclear. In this study, we investigated the analgesic effect and site of action of mirogabalin using the rat formalin test, an acute inflammatory pain model. Mirogabalin was administered orally, intrathecally, and intracerebroventricularly. Open field tests were performed to evaluate the effect of oral-, intrathecally, and intracerebroventricularly administered mirogabalin on locomotor activity and orientation ability. Oral mirogabalin produced an analgesic effect when the formalin test was performed 4 h, but not 1 or 2 h, after oral administration. Intrathecal, but not intracerebroventricular, administration of mirogabalin produced analgesic effects when mirogabalin was administered 10 min before formalin injection. These analgesic effects were not antagonized by idazoxan, an α2 adrenergic antagonist; WAY100135, a 5-HT1A antagonist; or naloxone, an opioid receptor antagonist. Mirogabalin attenuated moving distances 1 and 2 h after oral administration and 10 min after intracerebroventricular administration, but not 10 min after intrathecal administration. In the oral administration group, the time course of the analgesic effect was different from that of moving distance. In the intracerebroventricular group, mirogabalin attenuated moving distances but did not produce an analgesic effect. In the intrathecal group, mirogabalin produced an analgesic effect but did not affect moving distances. These findings suggest that the analgesic effect of mirogabalin on the rat formalin test is mediated by spinal action and not by the activation of α2, 5-HT1A, or opioid receptors, and that the inhibitory effect of mirogabalin on moving distances is mediated by the supraspinal brain.