Role of spinal neuronal nitric oxide synthase in neuropathic pain in rats

Abstract

Objective To investigate the role of spinal neuronal nitric oxide synthase(nNOS)in neuropathic pain in rats.Methods Male SD rots weighing 220-280 g were used in this study.The rats were implanted with chronic intrathecal(IT)catheters.Forty rats with normal motor function were randomly divided into4 groups(n = 10 each): group Ⅰ sham operation+7-nitorindaxole(7-NI);group Ⅱ sham operation+DMSO;group Ⅲ CCI+7-NI and group Ⅳ CCI+DMSO.Neuropathic pain was induced by chronic constrictive injury(CCI).Right sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0chromic catgut.In sham operation groups right sciatic nerve was exposed but not ligated.In group Ⅰ and Ⅲ 7-NI(a selective nNOS inhibitor)60 μg in 20% DMSO 10 μl was injected IT once a day for 6 consecutive days while in group Ⅱ and Ⅳ only the solvent 20% DMSO 10 μl was injected IT instead of 7-NI.Paw withdrawal threshold(PWT)to mechanical stimulation with von Frey filaments and paw withdrawal latency(PWL)to radiant beat were measured before operation(baseline)and at 1,3,5,7 d after operation.Five animals in each group were killed on the 7th day after operation after last pain threshold measurement.The dorsal root ganglions(DRGs)of the lumbar segment(L_(4-6))were removed for determination of the expression of nNOS mRNA(by RT-PCR)and protein(by Western blot).Results CCI significantly decreased the mechanical and thermal pain thresholds and increased the expression of nNOS mRNA and protein in the ipsilateral DRGs.IT 7-NI administration significantly suppressed the expression of nNOS in the lumbar DRGs and significantly attenuated CCI-induced mechanical allodynia and thermal hyperalgesia.Conclusion The spinal nNOS is involved in the formation of neuropathic pain. Key words: Neuralgia; Injections,spinal; Nitric oxide synthase