Redox modulation of peripheral T-type Ca2+ channels in vivo: alteration of nerve injury-induced thermal hyperalgesia.

We reported recently that redox agents, including the endogenous amino acid L-cysteine, modulate T-type Ca2+ currents in primary sensory neurons in vitro, and alter mechanical and thermal nociception in peripheral nociceptors in vivo in intact animals [Neuron 31 (2001) 75]. Here, we studied the effects of locally applied redox agents (L-cysteine and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) on thermal hyperalgesia in animals with neuropathic pain due to chronic constrictive injury (CCI) of the sciatic nerve. We found that, following injection into the peripheral receptive fields, the endogenous reducing agent L-cysteine increased thermal hyperalgesia in a dose-dependent manner in rats with CCI of the sciatic nerve as well as in sham-operated rats.

Mechanical and thermal anti-nociception in rats after systemic administration of verapamil.

Voltage-gated Ca(2+) channels expressed in neurons may contribute to nociceptive information processing. However, the role of L-type Ca(2+) channels in pain transmission is not well understood. In this study, we examined the effects of systemically administered verapamil, an antihypertensive agent and L-type Ca(2+) channel blocker, on mechanical and thermal withdrawal thresholds in rats.

Mechanical and thermal antinociception in rats following systemic administration of mibefradil, a T-type calcium channel blocker.

Voltage-gated Ca(2+) channels play a crucial role in pain perception. We studied the antinociceptive potential of systemically administered mibefradil, a peripherally acting antihypertensive agent and preferential T-type Ca(2+) channel blocker. Systemic injections of mibefradil, in clinically relevant doses, induced mechanical and thermal antinociception in adult rats without compromising their sensorimotor abilities.