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ANESTHETIC PHARMACOLOGY

Dexmedetomidine Enhances the Local Anesthetic Action of Lidocaine via an -2A Adrenoceptor

Tatsushi Yoshitomi, DDS^*, Atsushi Kohjitani, DDS, PhD, Shigeru Maeda, DDS, PhD^*, Hitoshi Higuchi, DDS, PhD^*, Masahiko Shimada, DDS, PhD, and Takuya Miyawaki, DDS, PhD^*

From the *Department of Dental Anesthesiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Japan; Department of Dental Anesthesiology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan; and Orofacial Pain Management, Department of Oral Restitution Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.

Address correspondence and reprint requests to Takuya Miyawaki, DDS, PhD, Department of Dental Anesthesiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8525, Japan. Address e-mail to miyawaki{at}md.okayama-u.ac.jp.

BACKGROUND: Clonidine, an -2 adrenoceptor agonist, is a common adjunct in both central and peripheral blocks. Dexmedetomidine, a more selective -2 adrenoceptor agonist, is also known to enhance central neural blockades. Its peripheral effect, however, has not been fully elucidated. Thus, we evaluated the effect of dexmedetomidine and other -2 adrenoceptor agonists on the local anesthetic action of lidocaine at the periphery and explored the mechanism involved.

METHODS: -2 Adrenoceptor agonists, including dexmedetomidine, clonidine, and oxymetazoline, combined with lidocaine were intracutaneously injected into the back of male guinea pigs. The test of six pinpricks was applied every 5 min until 60 min after the injection. The number of times which the prick failed to elicit a response during the 60-min period was added and the sum served as an anesthetic score indicating the degree of local anesthesia. Differences from the control value within the group were analyzed using an analysis of variance followed by a post hoc Dunnett’s test. Furthermore, we evaluated the antagonism of the effect of dexmedetomidine by yohimbine, an -2A, 2B, and 2C adrenoceptor antagonist, or prazosin, an -1, -2B, and 2C adrenoceptor antagonist, analyzed using a two-way analysis of variance.

RESULTS: All -2 adrenoceptor agonists enhanced the degree of local anesthesia of lidocaine in a dose-dependent manner. Furthermore, yohimbine inhibited the effect of dexmedetomidine, whereas prazosin did not.

CONCLUSION: We demonstrated that -2 adrenoceptor agonists enhanced the local anesthetic action of lidocaine, and suggest that dexmedetomidine acts via -2A adrenoceptors.

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999