Effect Of Intrathecal Midazolam On C-fos Expression In Dorsal Horn Of Spinal Cord In A Rat Model Of Peripheral Pain

Objective To investigate the median effective dose of intrathecal midazolam and the expression of c-fos in dorsal horn of spinal cord in a rat model of peripheral pain.Methods The experiment was performed in 2 parts.In part one,the median effective dose of intrathecal midazolam was obtained.In part two,the lumbar segmen of spinal cord was removed for determination of c-fos expression by immuno-histoehemistry.Thirty-two male SD rats were randomly divided into 4 groups(n=8 each):groupâ… control(C);groupâ…¡IT-NS+ PP(NS);groupâ…¢IT-midazolam before PP(M₁);groupâ…£IT midazolam afterPP(M₂);Peripheral pain(PP) was induced by injection of 5%formalin 100μ1 into the plantar surface of left hindpaw in groupâ…¡,â…¢andâ…£.100μ1 Normal saline(NS) was injected into the plantar surface of left hindpaw in groupâ… .A micro-catheter was inserted into subaraehnoid space in all animals.Normal saline 20μ1(groupâ… ,groupâ…¡)or the median effective dose of intrathecal midazolam 22μg(groupâ…¢)was injected intratheeally through the micro-catheter 10 rain before intraplantar formalin injection and midazolam 22μg(groupiv) was injected intratheeally after Peripheral pain.Pain behavior was assessed using mean flinching and licking time of the influenced limb. All the animals were killed at 2h after intraplantar formalin(or NS) injection after assessment of pain behavior and c-fos expression was determinate&Results The median effective analgesic dose(median value and 95%confidence interval) of intrathecal injection midazolam after peripheral pain was 21.8μg.The flinching and licking time of phaseâ…¡in groupâ…¡,groupâ…¢andâ…£was much longer than that in groupâ… (p＜0.01);The flinching and licking time of phaseâ…¡in groupâ…¢andâ…£was shorter than that in groupâ…¡(p＜0.01) and the time of phaseâ…¡in groupâ…¢was shorter than that in groupâ…£.(p＜0.01);The c-fos expression in dorsal horn of spinal cord was significantly higher in groupâ…¡than in groupâ… (control)but was significantly lower in groupâ…¢and group1â…¤(intrathecal midazolam)than that in groupâ…¡(P＜0.01).In group1â…¤The c-fos expression was higher than in groupâ…¢.Conclusion Intrathecal midazolam can inhibit the increase in c-fos expression in the spinal dorsal horn induced by intraplantar injection of formalin which is due to its antinociceptive and analgesic effects.Midazolam has preemptive analgesic effect at the spinal leve 1.