Evidence that spinal segmental nitric oxide mediates tachyphylaxis to peripheral local anesthetic nerve block

Background: Tachyphylaxis to sciatic nerve blockade in rats correlates with hyperalgesia, Spinal inhibition of nitric oxide synthase with N(G)nitro-L- arginine methyl ester (L-NAME) has been shown to prevent hyperalgesia. Give n systemically, L-NAME also prevents tachyphylaxis. The action of L-NAME in preventing tachyphylaxis therefore may be mediated at spinal sites. We com pared systemic versus intrathecal potency of L-NAME in modulating tachyphyl axis to sciatic nerve block. Methods: Rats were prepared with intrathecal catheters. Three sequential sc iatic nerve blocks were placed. Duration of block of thermal nocifensive, p roprioceptive and motor responses was recorded. We compared spinal versus s ystemic dose-response to L-NAME, and examined effects of intrathecal argini ne on tachyphylaxis. An additional group of rats underwent testing after TI O spinal cord transection. In these rats duration of sciatic nerve block wa s assessed by determining the heat-induced flexion withdrawal reflex. Results: L-NAME was 25-fold more potent in preventing tachyphylaxis given i ntrathecally than intraperitoneally. Intrathecal arginine augmented tachyph ylaxis. Spinalized rats exhibited tachyphylaxis to sciatic block. Conclusion: The increased potency of intrathecal versus systemic L-NAME sug gests a spinal site of action in inhibiting tachyphylaxis. Descending pathw ays are not necessary for the development of tachyphylaxis since it occurs even after TIO spinal cord transection. Thus tachyphylaxis, like hyperalges ia, is mediated at least in part by a spinal site of action.