Differential effects of bupivacaine and tetracaine on capsaicin-induced currents in dorsal root ganglion neurons

Capsaicin opens the TRPV1 channel, a cation channel that depolarizes and activates nociceptive neurons. Following this initial activation, neurons become desensitized to subsequent applications of capsaicin as well as to other noxious stimuli, a phenomenon attributed primarily to the entry of Ca2+ ions through the open TRPV1 channel. This ability of capsaicin to desensitize nociceptors has led to its use as an analgesic in the treatment of a variety of chronic pain states. Because treatment with capsaicin is initially quite painful, local anesthetics are sometimes used to block axonal conduction in nociceptive neurons and thus minimize pain. However, local anesthetics might also block TRPV1 and prevent the Ca2+ entry required for capsaicin-induced desensitization. We have studied the direct effect of local anesthetics on currents induced by capsaicin (1 μM) in acutely isolated rat dorsal root ganglion neurons using the whole cell patch clamp technique. At the highest concentration tested (1 mM), bupivacaine only moderately inhibited the capsaicin-induced current to 55 ± 27% of control (mean ± S.D.; n = 12, p < 0.01). Tetracaine (1 mM), on the other hand, enhanced the capsaicin-induced current to 151 ± 34% of control (mean ± S.D.; n = 7, p < 0.01). These results show that local anesthetics can be used to prevent the initial pain induced by application of capsaicin without abolishing, and perhaps even enhancing, its desensitizing actions.