title: The role of interleukin-1β in arthritic pain: main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis.
abstract: OBJECTIVE
  Interleukin-1β (IL-1β) is considered a pronociceptive cytokine, but its role in the generation of arthritic pain is unknown. The aim of this study was to investigate the role of IL-1β in arthritic pain and to explore the antinociceptive potential of the IL-1 receptor type I (IL-1RI) antagonist anakinra.
  
  
  METHODS
  Antigen-induced arthritis (AIA) was induced in rats. Expression of IL-1RI in the dorsal root ganglia (DRGs) was determined, and the effects of anakinra on inflammation, pain-related behavior, and receptor expression were assessed. In cultured DRG neurons, the effect of IL-1β on the expression of the transient receptor potential vanilloid 1 (TRPV-1) ion channel was examined. Recordings of action potentials from joint nociceptors were made after intraarticular injection of IL-1β into the rat knee joints.
  
  
  RESULTS
  AIA generated pronounced and persistent mechanical and thermal hyperalgesia, and IL-1RI expression in the lumbar DRGs was significantly up-regulated. Treatment with anakinra did not significantly reduce the severity of arthritis or mechanical hyperalgesia, but did result in a pronounced reduction in thermal hyperalgesia. In cultured DRG neurons, IL-1β up-regulated the expression of TRPV-1, a major transduction molecule involved in thermal hyperalgesia. During AIA, anakinra treatment down-regulated the expression of TRPV-1, consistent with the pronounced reduction in thermal hyperalgesia. IL-1β increased the mechanosensitivity of C-fibers of the joint, but reduced the mechanosensitivity of Aδ-fibers, thus having opposite effects on these mechanonociceptive nerve fibers.
  
  
  CONCLUSIONS
  In the context of arthritic knee pain, IL-1β and IL-1 receptors appear to be involved in thermal, rather than mechanical, hyperalgesia. Therefore, neutralization of IL-1β may be mainly antinociceptive in disease states characterized by thermal hyperalgesia, but not in disease states mainly characterized by mechanical hyperalgesia.
authors.affiliation: Jena University Hospital-Friedrich Schiller University of Jena, Jena, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Ebbinghaus
authors.forename: Benjamin
authors.initials: B
authors.lastname: Uhlig
authors.forename: Frank
authors.initials: F
authors.lastname: Richter
authors.forename: Gisela Segond
authors.initials: GS
authors.lastname: von Banchet
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Gajda
authors.forename: Rolf
authors.initials: R
authors.lastname: Bräuer
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Schaible
mesh_terms: D000818:Animals; D000941:Antigens / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D018771:Arthralgia / Q000188:drug therapy / Q000503:physiopathology*; D001169:Arthritis, Experimental / Q000139:chemically induced* / Q000188:drug therapy / Q000503:physiopathology*; D001696:Biomechanical Phenomena / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006930:Hyperalgesia / Q000503:physiopathology*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000494:pharmacology / Q000502:physiology*; D007719:Knee Joint / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D011917:Rats, Inbred Lew; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000941:Antigens; D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat