DAMGO, a micro-opioid agonist and cholecystokinin-octapeptide have dual modulatory effects on capsaicin-activated current in rat dorsal root ganglion neurons

ABSTRACT

Capsaicin, a pungent ingredient of hot pepper, elicits an intense burning pain when applied cutaneously and intradermally. Activation of capsaicin-gated channel in. C-type dorsal root ganglion (DRG) neurons produces nonselective cationic currents. Although electrophysiological and biochemical properties of capsaicin-activated current (ICAP) were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of ICAP by DAMGO (micro-opioid agonist) and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of ICAP was significantly increased by DAMGO and completely reversed after washout, while ICAP was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on ICAP. Mean action potential duration was significantly different between 'increased-by-DAMGO' group and 'decreased-by-DAMGO' group. Mean amplitudes of IH were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of ICAP (5/13). DAMGO also increased ICAP amplitude significantly in the same cells. The amplitude of ICAP was increased in additive manner by combined applications of DAMGO and CCK-8 in these cells. These results suggest that DAMGO and CCK-8 can either increase or decrease ICAP presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.