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Locally Injected Dexmedetomidine Inhibits Carrageenin-Induced Inflammatory Responses in the Injected Region

Sukegawa, Shintaro DDS*; Higuchi, Hitoshi DDS, PhD; Inoue, Miho PhD; Nagatsuka, Hitoshi DDS, PhD§; Maeda, Shigeru DDS, PhD; Miyawaki, Takuya DDS, PhD*

doi: 10.1213/ANE.0000000000000060
Pain and Analgesic Mechanisms: Research Report

BACKGROUND: Dexmedetomidine, a highly selective agonist of α2-adrenoceptors, is a commonly used sedative; however, a potent anti-inflammatory effect has also been found. In the present study we evaluated the inhibitory effect of locally injected dexmedetomidine on inflammatory responses in the injected region.

METHODS: Local inflammation was induced in the hindpaws of male mice (aged 6–8 weeks) by intraplantar injection of lambda-carrageenin. To offset the central effect of tested agents, different agents were blindly injected into the left and right paws in the pairs of comparison. The effect of dexmedetomidine on edema (increase in paw volume), the accumulation of leukocytes, and production of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) were evaluated after carrageenin injection, using water displacement plethysmometry, histological imaging, immunohistochemistry, and Western blotting analysis. Furthermore, we also evaluated the effect of yohimbine, a full antagonist of α2-adrenoceptors, and phenylephrine, an agonist of the α1-adrenoceptor, on dexmedetomidine’s action on inflammatory responses.

RESULTS: Paw volume and amount of leukocytes in the injected region significantly increased after the injection of carrageenin. Similarly, TNF-α and COX-2 production was found in the subcutaneous region injected with carrageenin, 4 hours after injection. Dexmedetomidine significantly inhibited all increases in paw volume, leukocytes, and production of TNF-α and COX-2. Furthermore, yohimbine significantly antagonized the anti-inflammatory effects of dexmedetomidine, whereas phenylephrine did not significantly alter them.

CONCLUSIONS: The findings suggest that locally injected dexmedetomidine exhibits an anti-inflammatory effect against local acute inflammatory responses, mediated by α2-adrenoceptors.

From the *Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences; Department of Dental Anesthesiology, Okayama University Hospital; Okayama University Dental School; and §Department of Oral Pathology and Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Accepted for publication November 1, 2013.

Funding: This study was supported by Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and the Accelerating Utilization of University Intellectual Property Program of the Japan Science and Technology Agency.

The authors declare no conflicts of interest.

Shintaro Sukegawa, DDS, and Hitoshi Higuchi, DDS, PhD, are co-first authors and contributed equally to this manuscript.

This report was previously presented, in part, at the 2011 American Society of Anesthesiologists meeting.

Reprints will not be available from the authors.

Address correspondence to Takuya Miyawaki, DDS, PhD, Department of Dental Anesthesiology and Special Care Dentistry Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700–8525, Japan. Address e-mail to

© 2014 International Anesthesia Research Society