Tetrodotoxin, Epinephrine, and Chemical Permeation Enhancer Combinations in Peripheral Nerve Blockade.

Abstract

Chemical permeation enhancers (CPEs) have the potential to improve nerve blockade by site 1 sodium channel blockers such as tetrodotoxin (TTX). Here, we investigated the efficacy and toxicity of CPE-enhanced nerve blockade across a range of TTX concentrations using 2 CPEs (sodium octyl sulfate and octyl trimethyl ammonium bromide). We also tested the hypothesis that CPEs could be used to reduce the concentrations of TTX and/or of a second adjuvant drug (in this case, epinephrine) needed to achieve prolonged local anesthesia METHODS:: Sprague-Dawley rats were injected at the sciatic nerve with combinations of TTX and CPEs, with and without epinephrine. Sensory and motor nerve blockade were assessed using a modified hot plate test and a weight-bearing test, respectively. Systemic and local toxicities of the different combinations were assessed. Addition of increasing concentrations of TTX to fixed concentrations of CPEs produced a marked concentration-dependent improvement in the rate of successful nerve blocks and in nerve block duration. CPEs did not affect systemic toxicity. At some concentrations, the addition of sodium octyl sulfate increased the duration of block from TTX plus epinephrine, and epinephrine increased that from TTX plus CPEs. The addition of epinephrine did not cause an increase in local toxicity, and it markedly reduced systemic toxicity. CPEs can prolong the duration of nerve blockade across a range of concentrations of TTX. CPEs could also be used to reduce the concentration of epinephrine needed to achieve a given degree of nerve block. CPEs may be useful in enhancing nerve blockade from site 1 sodium channel blockers.