Synergistic interaction of guanfacine or dexmedetomidine coadministered with lidocaine for cutaneous analgesia in rats

Background: This study examined the cutaneous analgesic effects of lidocaine co-injected with guanfacine and its comparison with dexmedetomidine. Methods: Cutaneous analgesic effects are quantified through the blocking effects of the cutaneous trunci muscle reflex against skin pinpricks in rats. The dose-response curves of guanfacine, dexmedetomidine, and lidocaine were constructed and drug-drug interactions were analyzed by the ED₅₀ isobologram. Results: Subcutaneous injections of guanfacine, dexmedetomidine, and lidocaine produced dose-dependently nociceptive/sensory blockade. On the ED₅₀ (50% effective dose) basis, the potency rankings of the drug are dexmedetomidine (0.09 [0.08–0.11] μmol/kg) > guanfacine (3.98 [2.96–5.34] μmol/kg) > lidocaine (25.40 [23.51–27.44] μmol/kg) (p < 0.01). On their equipotent doses (ED₂₅, ED₅₀, and ED₇₅), the duration of sensory blockade induced by guanfacine or dexmedetomidine was longer than lidocaine’s (p < 0.01). Both guanfacine and dexmedetomidine showed synergistic effects with lidocaine. Conclusions: We showed that guanfacine elicits dose-dependent cutaneous analgesia when administered subcutaneously. Lidocaine is less potent than guanfacine or dexmedetomidine. Both guanfacine and dexmedetomidine enhance the potency and duration of lidocaine. Better synergistic responses we are getting with guanfacine plus lidocaine.