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Anesth Analg 2007;105:245-250
© 2007 International Anesthesia Research Society
doi: 10.1213/01.ane.0000265850.08385.a6

ANALGESIA

Peripheral Suppression of Arthritic Pain by Intraarticular Fadolmidine, an {alpha}2-Adrenoceptor Agonist, in the Rat

Osei B. Ansah, DVM, PhD, and Antti Pertovaara, MD, PhD

From the Biomedicum Helsinki, Institute of Biomedicine/Physiology, University of Helsinki, Helsinki, Finland.

Address correspondence and reprint requests to A. Pertovaara, MD, PhD, Biomedicum Helsinki, Institute of Biomedicine/Physiology, POB 63, University of Helsinki, FIN-00014 Helsinki, Finland. Address e-mail to antti.pertovaara{at}helsinki.fi.

Abstract

BACKGROUND: Earlier results suggest that peripheral {alpha}2-adrenoceptors and opioid receptors may reduce arthritic pain. Fadolmidine is a highly selective {alpha}2-adrenoceptor agonist that has only limited central access after peripheral administration. We assessed the peripheral antinociceptive properties of fadolmidine and the potential contribution of peripheral opioid receptors to its antinociceptive effect in experimental monoarthritis.

METHODS: After induction of monoarthritis in the knee joints of rats, we determined the frequency of vocalization induced by repetitive movement of the knee joint. Fadolmidine and clonidine were administered intraarticularly ipsi- or contralateral to the inflamed joint. Reversal of the fadolmidine-induced effect was attempted with subcutaneous (s.c.) administration of atipamezole, an {alpha}2-adrenoceptor antagonist, and intraarticular administration of naloxone methiodide, an opioid receptor antagonist that does not penetrate the blood–brain barrier.

RESULTS: Fadolmidine produced a dose-dependent attenuation of the vocalization response to movement of the inflamed knee joint, and this effect was significantly stronger after ipsi- than contralateral drug administration. Clonidine also produced a dose-dependent attenuation of the vocalization response, but this effect was not significantly different after ipsi- versus contralateral drug administration. Fadolmidine-induced antinociception was reversed by s.c. administration of atipamezole. Furthermore, intraarticular administration of naloxone methiodide into the inflamed, but not the contralateral, joint reversed the antinociceptive effect of fadolmidine independent of whether fadolmidine was administered into the inflamed or contralateral joint.

CONCLUSIONS: In rats, intraarticular administration of fadolmidine provides a marked suppression of pain-related behavior in arthritis, due to a selective action on peripheral {alpha}2-adrenoceptors and opioid receptors.




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Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 2007 by the International Anesthesia Research Society.