The Mechanism of R-PIA Induced Mechanical Antiallodynia in a Peripheral Neuropathic Rat

Abstract

The injury by a nerve ligation produces a mechanical allodynia. The antiallodynic effect resulted from intrathecal administration of the adenosine analogues has been well known. ATP-sensitive potassium channel blockers have been known to reverse the effect of some antinociceptive drugs in animal and human studies. Therefore, the present study is to assess the relationship between antiallodynic effect of N6-(R)-phenylisopropyl adenosine (R-PIA) and mitochondrial ATP-sensitive potassium (mKATP) channel in a neuropathic pain model. Methods: Allodynia was induced in male Sprague Dawley rats by the tight ligation of the left lumbar 5th and 6th spinal nerves. We tested the mechanical allodynia by pricking von Frey filaments to the left hind paw and assessed withdrawal thresholds of paw with up-down method. For the estimation of the antiallodynic effect of R-PIA, R-PIA (0.5, 1 and 2μg) or saline were administered intrathecally.To investigate the reversal effect on antiallodynic effect of R-PIA, variable amounts of 5-hydroxydecanoate (5-HD, 20, 30 and 40 mg), mKATP channel blocker were administered intraperitoneally at 5 min prior to the intrathecal injection of 2μg of R-PIA, and the degree of allodynia was assessed. Results: The paw withdrawal threshold was gradually increased with increased dose of R-PIA and reached the maximum level with 2μg R-PIA (P ＜ 0.05). The increase of paw withdrawal threshold with 2μg R-PIA was significantly reversed dose-dependently by intraperitoneal pretreatment of 20, 30 and 40 mg/kg 5-HD (P ＜ 0.05). Conclusions: In our results, intraperitoneal injection of 5-HD before intrathecal injection of R-PIA had reversed the antiallodynic effect of R-PIA. This results suggest that the mechanism of mechanical antiallodynia induced by intrathecal injection of R-PIA may relate with the mKATP channel in a rat model of nerve ligation injury.