Endogenous opioid analgesia in peripheral tissues and the clinical implications for pain control

(2005) Views  (267) Full article downloads

Authors: Daniel Kapitzke, Irina Vetter, Peter J Cabot

Published Date January 2005 Volume 2005:1(4) Pages 279 - 297

DOI: http://dx.doi.org/10.2147/TCRM.S

Daniel Kapitzke^1,2, Irina Vetter^1,2, Peter J Cabot²

¹These authors contributed equally to this work. ²School of Pharmacy, University of Queensland, 4072, Australia

Abstract: Opioid receptors are widely expressed in the central and peripheral nervous system as well as in numerous nonneuronal tissues. Both animal models and human clinical data support the involvement of peripheral opioid receptors in analgesia, particularly in inflammation where both opioid receptor expression and efficacy are increased. Immune cells have been shown to contain numerous opioid peptides such as β-endorphin (END), met-enkephalin (ENK), and dynorphin-A (DYN), although the predominant opioid peptide involved in immunecell mediated antinociception is thought to be END. These opioid-containing immune cells migrate to inflamed tissues during a complex process of recruitment by chemokines, adhesion, and extravasation. In these tissues, opioid peptide is released from the immune cells upon stimulation with corticotrophin-releasing factor (CRF), noradrenaline, and interleukin 1β (IL-1β), and the immune cells return to the local lymph node depleted of peptide. Consistent with this model, systemic immunosuppression may lead to impaired endogenous analgesia as competent immune cells are essential to achieve release of endogenous opioid peptides within inflamed tissue. A further level of complexity is added by the observation that exogenous opioids may impair immune cell function, although there is some evidence to suggest that endogenous opioid peptides do not share this immunosuppressive effect. Improving our understanding of endogenous opioid mechanisms will provide valuable insight towards the development of novel treatments for pain with improved side effect profiles.

Keywords: Opioid, analgesia, inflammation, immunosuppression, immune cell, pain