Mexiletine co-injected with clonidine increases the quality and duration of cutaneous analgesia in response to skin pinpricks in the rat

The goal of the experimental design was to assess the cutaneous analgesic effect of mexiletine by co-injection with clonidine. The effect of nociceptive block was evaluated according to the inhibition of the cutaneous trunci muscle reflex (CTMR) in response to skin pinpricks in rats. The dose-related analgesic effect of mexiletine alone or mexiletine co-administrated with clonidine was constructed after subcutaneous injection. Subcutaneous injections of mexiletine elicited dose-related cutaneous analgesia. Compared with mexiletine (1.8 μmol), adding clonidine to mexiletine (1.8 μmol) solutions for skin nociceptive block potentiated and prolonged the action (p < 0.01). Mexiletine (6 μmol) combined with clonidine extended the duration of cutaneous analgesia when compared with mexiletine (6 μmol) alone (p < 0.01). Co-administration of clonidine increases the potency and extends the duration of cutaneous analgesia by mexiletine, and the minimal dose of clonidine to intensify the analgesic effect is 0.06 μmol.