Abstract
It is well-known that capsaicin (Caps) activates TRPV1s existing in the peripheral and central terminals of primary-afferent fibers; the peripheral activation of TRPV1 produces action potentials and the central activation of TRPV1 leads to a barrage of the spontaneous release of L-glutamate from nerve terminals to spinal dorsal horn neurons. Although Caps was reported to produce a nerve conduction block, this action has not been thoroughly examined yet. We examined the actions of Caps and its analogs on Na+-channel blocker tetrodotoxin-sensitive and fast-conducting compound action potentials (CAPs) recorded from the frog sciatic nerve by use of the air-gap method.Caps reversibly reduced the peak amplitude of the CAP in a dose-dependent manner (by about 50% at 200 µM). Although a TRPV1 antagonist capsazepine (50 µM) by itself inhibited CAPs, this drug did not affect the Caps-induced inhibition of CAP. A TRPV1 agonist resiniferatoxin (5 µM) had no effect on CAPs. Caps analogs, dihydrocapsaicin, zingerone, eugenol and vanillin, also inhibited CAPs in a reversible and dose-dependent manner. A potency sequence of these inhibitions was Caps = dihydrocapsaicin > eugenol >> zingerone ≥ vanillin >> vanillylamine. Other Caps analog, vanillic acid, had almost no effect on CAPs. A TRPV1 agonist, olvanil, at 30 µM, a maximal concentration to dissolve this drug in Ringer solution, was less effective than was Caps in inhibiting CAPs. It is concluded that Caps inhibits CAPs without TRPV1 activation and that a chemical structure bound to the vanillyl group of Caps analogs plays a role in determining the extent of CAP inhibition. These results may serve to know molecular mechanisms for Caps-induced conduction block.
