Role of NO/cGMP signaling pathway in dexmedetomidine-induced reduction of neuropathic pain in rats

Abstract

Objective To investigate the role of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling pathway in dexmedetomidine-induced reduction of neuropathic pain (NP) in the rats. Methods Forty-two healthy male Sprague-Dawley rats, weighing 200-250 g, were randomly divided into 7 groups (n=6 each) using a random number table: normal control group (C group); NP group; dexmedetomidine group (D group); dimethyl sulfoxide (DMSO) group; a non-selective nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) group (L-NAME group); inactive enantiomer D-NAME group (D-NAME group); a soluble guanylyl cyclase inhibitor 1H-[1, 2, 4] oxidazole[4, 3-a] quinoxalin-1-one (ODQ) group (ODQ group). NP was induced by chronic constriction injury to the sciatic nerve in anesthetized rats.On day 7 after chronic constriction injury, dexmedetomidine 1.5 μg/kg was injected intrathecally in group D, and in DMSO, L-NAME, D-NAME and ODQ groups, DMSO 10 μl, L-NAME 100 μg, D-NAME 100 μg and ODQ 10 μg were injected intrathecally, respectively, and 25 min later dexmedetomidine 1.5 μg/kg was injected intrathecally.The thermal paw withdrawal latency was measured immediately after intrathecal administration and at 30, 60, 90, 120, 150, 180 and 210 min after intrathecal administration, and the area under the curve of thermal paw withdrawal latency was calculated to reflect the thermal pain threshold. Results Compared with group C, the thermal pain threshold was significantly decreased in the other six groups (P 0.05). Conclusion The mechanism by which dexmedetomidine reduces NP is related to activation of NO/cGMP signaling pathway in the rats. Key words: Dexmedetomidine; Neuralgia; Nitric oxide; Cyclic GMP; Spinal cord