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Anesth Analg 2008; 107:271-281
© 2008 International Anesthesia Research Society
doi: 10.1213/ane.0b013e318162cfa3
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PAIN MEDICINE

Vanilloid-Induced Conduction Analgesia: Selective, Dose-Dependent, Long-Lasting, with a Low Level of Potential Neurotoxicity

Igor Kissin, MD, PhD

From the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Address correspondence and reprint requests to Igor Kissin, MD, PhD, Pain Research Center, Brigham and Women's Hospital, 75 Francis St., MRB611, Boston, MA 02115. Address e-mail to kissin{at}zeus.bwh.harvard.edu.

Vanilloid agonists (capsaicin, resiniferatoxin, [RTX]) applied to the peripheral nerves provide conduction blockade. In contrast to the analgesic component of conduction anesthesia produced by local anesthetics, vanilloid agonists provide conduction analgesia not associated with suppression of motor or sensory functions not related to pain. Vanilloid agonists provide conduction analgesia selectively because their effect on the nerve trunks is limited to C- and A{Delta}-fibers. RTX is much more potent than capsaicin and has a wider therapeutic window. In rat experiments, perineural RTX produced a long-lasting thermal and mechanical hypoalgesia with a very wide separation between effective concentrations (from 0.00003% to 0.001%) providing an effect lasting from several hours to several weeks. A nerve block with RTX prevented the development of thermal and mechanical hyperalgesia as well as pain behavior in a model of incisional pain. RTX-induced conduction blockade has an inherent drawback of TRPV1 agonists, the initial excitation (pain); therefore, a local anesthetic should be injected to prevent it. When RTX was applied to the rat's sciatic nerve in doses necessary to provide conduction analgesia, the frequency of unmyelinated fiber degeneration was more than an order of magnitude lower than that with the therapeutic concentration of lidocaine. These promising results should be confirmed by experiments in species other than rodents (pigs, sheep). Taken together, the data indicate possible clinical applicability of vanilloid-induced conduction analgesia.




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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 © 2008 by the International Anesthesia Research Society.