Omega-agatoxin IVA, a P-type calcium channel antagonist, reduces nociceptive processing in spinal cord neurons with input from the inflamed but not from the normal knee joint--an electrophysiological study in the rat in vivo.

High threshold voltage-dependent P- and Q-type calcium channels are involved in neurotransmitter release. In order to investigate the role of P- and Q-type calcium channels in the mechanosensory (nociceptive) processing in the spinal cord, their participation in the responses of spinal wide-dynamic-range neurons to innocuous and noxious mechanical stimulation of the knee and ankle joints was studied in 30 anaesthetized rats. The knee was either normal or acutely inflamed by kaolin/carrageenan. During the topical application of omega-agatoxin IVA (P-type channel antagonist, 0.1 microM) onto the dorsal surface of the spinal cord, the responses to innocuous and noxious pressure applied to the normal knee were increased to respectively 124 +/- 42% and 114 +/- 23% of predrug values (mean +/- SD, P < 0.05, 14 neurons). By contrast, in rats with an inflamed knee, the responses to innocuous and noxious pressure applied to the knee were reduced to respectively 72 +/- 19 and 73 +/- 22% of baseline (mean +/- SD, P < 0.01, 13 neurons). In the same neurons, omega-agatoxin IVA slightly increased the responses to pressure on the non-inflamed ankle whether the knee was normal or inflamed. Thus P-type calcium channels seem to acquire a predominant importance in the excitation of spinal cord neurons by mechanosensory input from inflamed tissue and hence in the generation of inflammatory pain. By contrast, the Q-type channel antagonist, omega-conotoxin MVIIC (1 or 100 microM), had no significant effect upon responses to innocuous or noxious pressure applied to either normal or inflamed knees (25 neurons).