The Mechanism of R-PIA Induced Mechanical Antiallodynia in a Peripheral Neuropathic Rat. |
Woo Jong Choi, Young Ki Kim, Eun Young Shin, Jin Woo Shin, Ji Yeon Sim, Jeong Gil Leem, Chung Lee |
1Department of Anesthesiology and Pain Medicine, Asan Medical Center, Seoul, Korea. jinwoos@amc.seoul.kr 2Department of Anesthesiology and Pain Medicine, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, Korea. 3Department of Anesthesiology and Pain Medicine, Eulji University College of Medicine, Daejeon, Korea. |
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Abstract |
BACKGROUND 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 2microgram) 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 2microgram 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 2microgram R-PIA (P < 0.05). The increase of paw withdrawal threshold with 2microgram 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 mK(ATP) channel in a rat model of nerve ligation injury. |
Key Words:
adenosine receptor; allodynia; ATP-sensitive potassium channel; 5-hydroxydecanoate; N6-(R)-phenylisopropyl adenosine |
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