Abstract
Chemical permeation enhancers (CPEs) have the potential to improve access of local anesthetics to the nerve, thereby improving nerve block performance. We assessed the effects of six CPEs on nerve blockade from tetrodotoxin (TTX) and from bupivacaine. Each of the six surfactants, representing three CPE subgroups (anionic, cationic, and nonionic surfactants) was coinjected with TTX or bupivacaine at the sciatic nerve of Sprague-Dawley rats. Myotoxicity of CPEs, alone and with TTX, was assessed in vitro in C2C12 myotubes and in vivo via histological analysis. All enhancers produced marked concentration-dependent improvements in the frequency and duration of block with TTX but not bupivacaine. An in vitro toxicity assay showed a wide range of CPE myotoxicity, but in vivo histological assessment showed no signs of muscle or nerve damage at concentrations of CPEs that produced a half-maximal increase in the duration of block of TTX (except in the case of the cationic surfactant DDAB). This study demonstrates that CPEs can provide marked prolongation of nerve blockade from TTX but not bupivacaine, without apparent local tissue toxicity. These results may enhance the clinical applicability of TTX for prolonged-duration local anesthesia.
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