Analgesic effect of intrathecal SB203580 in a rat model of neuropathic pain / 中华麻醉学杂志

ABSTRACT

Objective To investigate the analgesic effect of a specific p38MAPK inhibitor SB203580 in a rat model of chronic constriction injury (CCI) to sciatic nerve. Methods Male SD rats weighing 220-250 g were used in this study. The neuropathic pain model was established by CCI to sciatic nerve. The rats were anesthetized with intraperitoneal (i.p.) pentobarbital 40 mg?kg-1. Left sciatic nerve was exposed and 4 loose ligatures were placed on left sciatic nerve at 1 mm intervals with 4-0 silk suture. The animals were allowed 7 days to recover from surgery. Intrathecal (IT) SB203S80 was given through a needle inserted at L5,6 interspace. In experiment A, 40 rats wee randomly divided into 5 groups (n = 8 each) control group and 4 SBgroups (SB203580 0.1, 0.5, 2.5 and 5.0 ?g were given respectively) . Response of the hindpaw to mechanical stimulation with von Frey filament (MWT) was measured before (T0,baseline) and at 0.5, 3, 6, 12 and 24 h (T1-5) after IT SB203580 injection. In experiment B, 36 animals were randomly divided into 6 groups (n = 6 each) (1) sham operation group; (2) CCI group; (3) DMSO group; (4) SB 0.1 ?g group; (5) SB 0.5 ?g group and (6) SB 5.0 ?g group. The animals were lulled at 6h after IT SB203580 administration and L5,6 lumbar segment of the spinal cord was removed for determination of pCREB expression in the dorsal horn by immuno-cytochemistry. Results The rats developed hyperalgesia after CCI and IT SB203580 administration significantly increased MWT in a dose dependent manner. The number of pCREB positive neurons in the L4,5 spinal dorsal horn was significantly increased after CCI. Interthecal administration of SB203580 0.5 or 5.0 ?g significantly inhibited the CCI-induced increase in pCREB expression. Conclusion Intrathecal administration of SB203580 can attenuate the hyperalgesia induced by CCI and inhibition of CREB phosphorylation in the spinal dorsal horn is involved in the mechanism.