N-G-NITRO-L-ARGININE METHYL-ESTER (L-NAME) PREVENTS TACHYPHYLAXIS TO LOCAL-ANESTHETICS IN A DOSE-DEPENDENT MANNER

A model of local anesthetic tachyphylaxis was developed in our group p reviously using repeated sciatic nerve blocks in rats. In this model, thermal hyperalgesia accelerated tachyphylaxis, and the noncompetitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, MK-801, prevente d both hyperalgesia and tachyphylaxis. Nitric oxide is thought to be a second messenger for NMDA pathways in the spinal cord, and appears to be involved in spinal mechanisms of hyperalgesia. We hypothesized tha t nitric oxide synthase inhibitors would also inhibit the development of tachyphylaxis. Repeated rat sciatic nerve blacks were placed by per cutaneous injection of 2-chloroprocaine. Block duration was tested by measuring hot-plate latency at 56 degrees C. Two hours before the firs t nerve block, rats received intraperitoneal injections with saline or one of six concentrations of N-G-nitro-L-arginine methyl ester (L-NAM E) in a randomized, blinded pattern. Control rats developed tachyphyla xis as seen previously: the duration of the third block was 30% that o f the first. L-NAME inhibited the development of tachyphylaxis in a do se-dependent manner; tachyphylaxis was inhibited by 50% using L-NAME a t 0.2 mg/kg and completely abolished by 50 mg/kg. Nitric oxide pathway s may be involved in the development of tachyphylaxis to local anesthe tic nerve block.