Acute, adverse skin effects to capsaicin can be activated by inhibition of sodium transport not only in nociceptive neurons, but also in keratinocytes. The aim of the current study was to describe and compare immediate (15 s) and prolonged (30 min) effects of capsaicin on epidermal (not neural) sodium transport using a rabbit skin model. Skin fragments (n = 169) were incubated in 4 conditions: undisturbed ion transport (U; n = 48); inhibited sodium transport (INa; n = 34) with amiloride used as sodium transport blocker; long-term irritation by capsaicin with undisturbed ion transport (CAPSA-U; n = 43) and with inhibited sodium transport (CAPSA-INa; n = 35). After 30 min of incubation, a solution of capsaicin was applied directly to the skin fragments. The study demonstrated that sodium transport inhibition eliminated the effects of both immediate and prolonged capsaicin application. The results could be the basis for future research considering selective sodium transport inhibitors for human skin to reduce the side effects of capsaicin, related to activation of sodium channels in keratinocytes.

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