DAMGO, a μ-Opioid Agonist and Cholecystokinin-Octapeptide Have Dual Modulatory Effects on Capsaicin-Activated Current in Rat Dorsal Root Ganglion Neurons

DAMGO, a μ-Opioid Agonist and Cholecystokinin-Octapeptide Have Dual Modulatory Effects on Capsaicin-Activated Current in Rat Dorsal Root Ganglion Neurons

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<P> 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 (I<SUB>CAP</SUB>) were studied, the regulatory mechanism and intracellular signaling pathway are still unclear. In the present study, we investigated the modulations of I<SUB>CAP</SUB> by DAMGO (μ-opioid agonist) and cholecystokinin octapeptide (CCK-8). In 18 out of 86 cells, the amplitude of I<SUB>CAP</SUB> was significantly increased by DAMGO and completely reversed after washout, while I<SUB>CAP</SUB> was decreased by DAMGO in 25 cells. In 43 cells, DAMGO had no effect on I<SUB>CAP</SUB>. Mean action potential duration was significantly different between increased-by-DAMGO group and decreased-by-DAMGO group. Mean amplitudes of I<SUB>H</SUB> were not significantly different between both groups. CCK-8 reversibly enhanced the amplitude of I<SUB>CAP </SUB>(5/13). DAMGO also increased I<SUB>CAP</SUB> amplitude significantly in the same cells. The amplitude of I<SUB>CAP</SUB> 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 I<SUB>CAP</SUB> presumably depending on the subtypes of DRG cells and classified by electrophysiological properties.