Prolonged cutaneous analgesia in rats induced by 3‐acetylaconitine as an additive

3-Acetylaconitine (3AA) is an “aconitine-like” plant alkaloid that has been used as an analgesic agent for the treatment of chronic pain and rheumatoid arthritis in China. Aconitine-like alkaloids appear to target the CNS for their analgesic action, although they also display local anesthetic properties. We tested whether 3AA prolonged cutaneous analgesia in rats when co-injected with lidocaine (0.5%) and epinephrine (1:200,000), a mixture commonly used in infiltration anesthesia. Inhibition of the cutaneous trunci muscle reflex was evaluated quantitatively by pinpricks applied to the injected area. Co-injection of lidocaine and epinephrine with 3AA ranging within 50–125 µM elicited complete cutaneous analgesia in vivo lasting 3–12 h, and full recovery occurred after ∼5–8 days in a 3AA concentration-dependent manner. In contrast, cutaneous analgesia induced by the mixture of lidocaine and epinephrine or by 3AA alone in rats was significantly shorter. No adverse systemic effects or local toxicities were evident after injection of 3AA as an additive. Our results suggest that “aconitine-like” alkaloids could be exploited as an additive for long-lasting cutaneous analgesia. Drug Dev Res 69: 83–88, 2008. © 2008 Wiley-Liss, Inc.