title: Different mechanisms of intrinsic pain inhibition in early and late inflammation.
abstract: Neuroimmune interactions control pain through activation of opioid receptors on sensory nerves by immune-derived opioid peptides. Here we evaluate mechanisms of intrinsic pain inhibition at different stages of Freund's adjuvant-induced inflammation of the rat paw. We use immunohistochemistry and paw pressure testing. Our data show that in early (6 h) inflammation leukocyte-derived beta-endorphin, met-enkephalin and dynorphin A activate peripheral mu-, delta- and kappa-receptors to inhibit nociception. In addition, central opioid mechanisms seem to contribute significantly to this effect. At later stages (4 days), antinociception is exclusively produced by leukocyte-derived beta-endorphin acting at peripheral mu and delta receptors. Corticotropin-releasing hormone (CRH) is an endogenous trigger of these effects at both stages. These findings indicate that peripheral opioid mechanisms of pain inhibition gain functional relevance with the chronicity of inflammation.
authors.affiliation: Klinikum Benjamin Franklin, Freie Universität Berlin, D-12200 Berlin, Germany. MACHELSKA@zop-admin.ukbf.fu-berlin.de
authors.forename: Halina
authors.initials: H
authors.lastname: Machelska
authors.forename: Julia K
authors.initials: JK
authors.lastname: Schopohl
authors.forename: Shaaban A
authors.initials: SA
authors.lastname: Mousa
authors.forename: Dominika
authors.initials: D
authors.lastname: Labuz
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfer
authors.forename: Christoph
authors.initials: C
authors.lastname: Stein
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D004399:Dynorphins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D004487:Edema / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D004723:Endorphins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D004744:Enkephalin, Methionine / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology; D005620:Freund's Adjuvant / Q000008:administration & dosage; D006614:Hindlimb; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D007279:Injections, Subcutaneous; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008297:Male; D009270:Naloxone / Q000008:administration & dosage; D010146:Pain / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*; D017288:Pain Threshold; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors
chemical_list: D004723:Endorphins; D009270:Naloxone; D004744:Enkephalin, Methionine; D004399:Dynorphins; D005620:Freund's Adjuvant; D003346:Corticotropin-Releasing Hormone