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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.

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