Capsaicin, the pungent ingredient in hot pepper, activates nociceptors to produce pain and inflammation. However, prolonged exposures of capsaicin will cause desensitization to nociceptive stimuli. Hyperpolarization-activated cation currents (I_h) contribute to the maintenance of the resting membrane potential and excitability of neurons. In the cultured dorsal root ganglion (DRG) neurons, we investigated mechanisms underlying capsaicin-mediated modulation of I_h using patch clamp recordings. Capsaicin (1 µM) inhibited I_h only in the capsaicin-sensitive neurons. The capsaicin-induced inhibition of I_h was prevented by preexposing the TRPV1 antagonist, capsazepine (CPZ). Capsaicin-induced inhibition of I_h was dose dependent (IC₅₀= 0.68 µM) and partially abolished by intracellular BAPTA and cyclosporin A, specific calcineurin inhibitor. In summary, the inhibitory effects of capsaicin on I_h are mediated by activation of TRPV1 and Ca²⁺-triggered cellular responses. Analgesic effects of capsaicin have been thought to be related to desensitization of nociceptive neurons due to depletion of pain-related substances. In addition, capsaicin-induced inhibition of I_h is likely to be important in understanding the analgesic mechanism of capsaicin.

Keywords: capsaicin, DRG neuron, hyperpolarization-activated cation current, rat