Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/68981
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Type: Journal article
Title: Exploring the neuroimmunopharmacology of opioids: An integrative review of mechanisms of central immune signaling and their implications for opioid analgesia
Author: Hutchinson, M.
Shavit, Y.
Grace, P.
Rice, K.
Maier, S.
Watkins, L.
Citation: Pharmacological Reviews, 2011; 63(3):772-810
Publisher: American Society of Pharmacology Experimental Therapeutics
Issue Date: 2011
ISSN: 0031-6997
1521-0081
Statement of
Responsibility: 
Mark R. Hutchinson, Yehuda Shavit, Peter M. Grace, Kenner C. Rice, Steven F. Maier, and Linda R. Watkins
Abstract: Vastly stimulated by the discovery of opioid receptors in the early 1970s, preclinical and clinical research was directed at the study of stereoselective neuronal actions of opioids, especially those played in their crucial analgesic role. However, during the past decade, a new appreciation of the non-neuronal actions of opioids has emerged from preclinical research, with specific appreciation for the nonclassic and nonstereoselective sites of action. Opioid activity at Toll-like receptors, newly recognized innate immune pattern recognition receptors, adds substantially to this unfolding story. It is now apparent from molecular and rodent data that these newly identified signaling events significantly modify the pharmacodynamics of opioids by eliciting proinflammatory reactivity from glia, the immunocompetent cells of the central nervous system. These central immune signaling events, including the release of cytokines and chemokines and the associated disruption of glutamate homeostasis, cause elevated neuronal excitability, which subsequently decreases opioid analgesic efficacy and leads to heightened pain states. This review will examine the current preclinical literature of opioid-induced central immune signaling mediated by classic and nonclassic opioid receptors. A unification of the preclinical pharmacology, neuroscience, and immunology of opioids now provides new insights into common mechanisms of chronic pain, naive tolerance, analgesic tolerance, opioid-induced hyperalgesia, and allodynia. Novel pharmacological targets for future drug development are discussed in the hope that disease-modifying chronic pain treatments arising from the appreciation of opioid-induced central immune signaling may become practical.
Keywords: Central Nervous System; Neurons; Immune System; Animals; Humans; Receptors, Opioid; Receptors, Interleukin-1; Nerve Tissue Proteins; Analgesics, Opioid; Narcotic Antagonists; Analgesia; Signal Transduction; Neuroimmunomodulation; Toll-Like Receptors; Molecular Targeted Therapy
Rights: U.S. Government work not protected by U.S. copyright
RMID: 0020111247
DOI: 10.1124/pr.110.004135
Grant ID: http://purl.org/au-research/grants/nhmrc/465423
http://purl.org/au-research/grants/arc/DP110100297
Appears in Collections:Pharmacology publications

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