Mechanisms of peripheral immune-cell-mediated analgesia in inflammation: clinical and therapeutic implications.
Peripheral mechanisms of endogenous pain control are significant. In peripheral inflamed tissue, an interaction between immune-cell-derived opioids and opioid receptors localized on sensory nerve terminals results in potent, clinically measurable analgesia. Opioid peptides and the mRNA encoding their precursor proteins are present in immune cells. These cells 'home' preferentially to injured tissue, where they secrete opioids to reduce pain. Investigation of the mechanisms underlying the migration of opioid-containing immune cells to inflamed tissue is an active area of research, with recent data demonstrating the importance of cell adhesion molecules in leukocyte adhesion to both the endothelium in vascular transmigration and to neurons within peripheral inflamed tissue. This review summarizes the physiological mechanisms and clinical significance of this unique endogenous peripheral analgesic pathway and discusses therapeutic implications for the development of novel targeted peripheral analgesics.
Hua
Susan
S
The School of Biomedical Sciences and Pharmacy, The University of Newcastle, New South Wales, Australia.
Cabot
Peter J
PJ
D000698:Analgesia / Q000379:methods*; D000818:Animals; D002448:Cell Adhesion / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D007962:Leukocytes / Q000378:metabolism; D008959:Models, Neurological; D009474:Neurons / Q000276:immunology*; D018847:Opioid Peptides / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism
D015815:Cell Adhesion Molecules; D018847:Opioid Peptides