| Objective: The present study was initiated to observe the effect ofintrathecal morphine and protein kinase C inhibitor on rat's painthreshold and changes of nervronal CGRP expression in rat spinal dorsalhorn following spared nerve injury of sciatic nerve,,and to explore themechanism of neuropathic pain and the effect of intrathecal morphine onthese changes.Methods: Thirty healthy male Sprague-Dawley rats (200-270g)were randomly devided into six groups(n=5,in each group): controlgroup(group C), non-operated group(group N), normal salinegroup(group NS), morphine group(group M), protein kinase C inhibitorgroup(group P), morphine and protein kinase C inhibitor group(groupMP).There weren't operative procedure in group C rats.The rats in otherfive groups were anesthetized with 10％Chlroral Hydrate and amicroapinal catheterwas insterted intrathecally into the lumbarregion(about 8cm) according to the method of Yaksh. After 5 days, group N involved exposure of the sciatic nerve and its branches without anylesion;the rats in group NS,group M,group P and group MP received alesion of two of the three terminal branchesof the sciatic nerve(tibial andcommon peroneal nerves) leaving the remaining sural nerve intact (thespared nerve injury model,SNI).group N and group NS were intrathecallyinjected 20μl normal saline;group M,group P and group MP wereintrathecally injected 10μg morphine,11μg Chelerythrine Chloride and10μg morphine+11μg Chelerythrine Chloride followed by 10μl normalsaline after 2 days post-surgery,respectively. Mechanical allodynia andradiogenic heat pain thresholds were measured pre-surgery and on day1,2 post-surgery and 30 min after intrathecally injection.2 hours afterintrathecally injection, all rats were killed,and the L5 spinal cord weredissected for determination of the expression of CGRP usingimmunohistochemical techniques.Result: (1) In each group,there were no difference on the statistics inpain threshold before pre-surgery (P＞0.05); (2) There were significantdifference on the statistics in pain threshold in group NS,M,P,MPas comparede with that in group C and group N (P＜0.01) on day 1,2post-surgery,but the radiant heat stimulus paw withdrawal latency was nochange in four groups.(3) In group M,group P and group MP,there wassignificant difference on the statistics in pain threshold 30minpost-injection when compared to pre-injection levels (P＞0.05), the radiant heat stimulus paw withdrawal latency was also noticeableprolonged(P＜0.05).However, the pain threshold 30min post-injection ingroup MP was higher than that in group M and group P;(4) The numberof CGRP immunoreactive soma in the superficial laminae of the L5spinal cord was significantly incressed significantly in group NS than thatin group C and group N(P＜0.05). The number of immunoreactive somain group M,group P and group MP decreased significantly compared withthat in group NS,and there was also difference the number ofimmunoreactive soma in group MP as compared with that in group M andgroup P(P＜0.05);(5) The immunoreactive soma quantity density ofCGRP was higher in group NS than those in group C and N(P＜0.05),butthe quantity density in group M. P and MP were lower than that in thegroup NS,and between group MPand group M or group P the quantitydensity was also different(P＜0.05). The immunoreactive soma opticaldensity of CGRP was higher in SNI model group than that in controlgroup(P＜0.05).Conclusions: (1) Hyperpathia may be caused in the injured sidelimbs of rats following spared nerve injury of sciatic nerve.Intrathecaladministration of morphine and protein kinase C inhibitor providesignificant antinociception in the rat of SNI model; (2)The pain of SNImodel can produced the increase of neuronal CGRP expression in ratspinal dorsal horn; (3) Intrathecal morphine and protein kinase C inhibitor significantly inhibited the increase of CGRP expression in rat spinaldorsal horn of SNI model, suggested the inhibition of CGRP pathway isone of the mechanisms for intrathecal morphine and protein kinase Cinhibitor antinociception.
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