Exploring the neuroimmunopharmacology of opioids: An integrative review of mechanisms of central immune signaling and their implications for opioid analgesia

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dc.contributor.authorHutchinson, M.
dc.contributor.authorShavit, Y.
dc.contributor.authorGrace, P.
dc.contributor.authorRice, K.
dc.contributor.authorMaier, S.
dc.contributor.authorWatkins, L.
dc.contributor.editorBarker, E.L.
dc.date.issued2011
dc.description.abstractVastly 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.
dc.description.statementofresponsibilityMark R. Hutchinson, Yehuda Shavit, Peter M. Grace, Kenner C. Rice, Steven F. Maier, and Linda R. Watkins
dc.identifier.citationPharmacological Reviews, 2011; 63(3):772-810
dc.identifier.doi10.1124/pr.110.004135
dc.identifier.issn0031-6997
dc.identifier.issn1521-0081
dc.identifier.orcidHutchinson, M. [0000-0003-2154-5950]
dc.identifier.orcidGrace, P. [0000-0002-8999-1220]
dc.identifier.urihttp://hdl.handle.net/2440/68981
dc.language.isoen
dc.publisherAmerican Society of Pharmacology Experimental Therapeutics
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/465423
dc.relation.granthttp://purl.org/au-research/grants/arc/DP110100297
dc.rightsU.S. Government work not protected by U.S. copyright
dc.source.urihttps://doi.org/10.1124/pr.110.004135
dc.subjectCentral Nervous System
dc.subjectNeurons
dc.subjectImmune System
dc.subjectAnimals
dc.subjectHumans
dc.subjectReceptors, Opioid
dc.subjectReceptors, Interleukin-1
dc.subjectNerve Tissue Proteins
dc.subjectAnalgesics, Opioid
dc.subjectNarcotic Antagonists
dc.subjectAnalgesia
dc.subjectSignal Transduction
dc.subjectNeuroimmunomodulation
dc.subjectToll-Like Receptors
dc.subjectMolecular Targeted Therapy
dc.titleExploring the neuroimmunopharmacology of opioids: An integrative review of mechanisms of central immune signaling and their implications for opioid analgesia
dc.typeJournal article
pubs.publication-statusPublished

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