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.
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