TRPV1 is a cation channel expressed in peripheral nociceptive pathways and its activation can trigger nociception signals to the brain. Ketamine is an intravenous anesthetic routinely used for anesthesia induction and with potent analgesic activity. Despite its proven depressant action on peripheral sensory pathways, the relationship between ketamine and TRPV1 receptors is still unclear. In this study, we evaluated the effect of ketamine injected peripherally in a rat model of spontaneous pain induced by capsaicin. We also investigated the effect of ketamine on Ca2+ transients in cultured dorsal root ganglia (DRG) neurons and HEK293 cells expressing the TRPV1 receptor (HEK-TRPV1 cells). Intraplantar administration of ketamine caused an unexpected increase in nocifensive behavior induced by capsaicin. Incubation of HEK-TRPV1 cells with 10 μM ketamine increased TRPV1 and PKCє phosphorylation. Ketamine potentiated capsaicin-induced Ca2+ transients in HEK-TRPV1 cells and DRG neurons. Ketamine also prevented TRPV1 receptor desensitization induced by successive applications of capsaicin. єV1-2, a PKCє inhibitor, reduced potentiation of capsaicin-induced Ca2+ transients by ketamine. Taken together, our data indicate that ketamine potentiates TRPV1 receptor sensitivity to capsaicin through a mechanism dependent on PKCє activity.
Keywords: Intracellular calcium signaling; Ketamine; Nociception; PKCє; TRPV1 receptor.
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