Capsaicin induces a slow inward current which is not mediated by substance P in substantia gelatinosa neurons of the rat spinal cord.

Whole-cell voltage-clamp techniques were employed to investigate a capsaicin-induced current in substantia gelatinosa (SG) neurons in the dorsal horn of adult rat spinal cord slices. Bath-applied capsaicin (2 microM) for 30 s activated a slow excitatory current having an amplitude of 21.3+/-6.3 pA and a duration of 93+/-13 s (n=10; V(H)=-70 mV). This capsaicin current was compared in amplitude under various conditions among different SG neurons. After either neonatal capsaicin treatment or sciatic-nerve transection, by which C-afferent fibers are known to degenerate, this capsaicin current was reduced in amplitude to 5.0+/-3.5 pA (n=8) or 4.5+/-2.3 pA (n=6), respectively. A non-N-methyl-D-aspartate (NMDA)-receptor antagonist, CNQX (10 microM), depressed greatly the capsaicin current to 4.0+/-1.3 pA (n=9). On the other hand, this current had an amplitude of 14.4+/-2.7 pA (n=10) in the presence of an NMDA-receptor antagonist, AP-5 (50 microM); this value was not significantly different from that in the control (P>0.05). Substance P (SP; 1-2 microM) superfused for 2 min had no detectable effect on all SG neurons examined (n=7). After SP washout, however, these cells exhibited a capsaicin current (22.8+/-12.1 pA); this current persisted in the presence of a neurokinin-1 receptor antagonist, L-732,138 (1 microM; 19.8+/-3.5pA, n=9). The capsaicin current was not abolished by an intracellular dialysis with GDP-beta-S (1 mM; 20. 2+/-2.4 pA, n=9) which inhibited a baclofen (10 microM) response mediated by the G-protein-coupled GABA(B) receptor. These results indicate that the capsaicin-induced current is mediated through the activation of C-fibers by non-NMDA receptors. This mechanism in SG neurons is different from that known in neurons in other laminae of the dorsal horn that is thought to be a direct action of SP released from C-fibers. This current in SG neurons would contribute to the pain sensation caused by capsaicin.