The role of interleukin-1β in arthritic pain: main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis

Arthritis Rheum. 2012 Dec;64(12):3897-907. doi: 10.1002/art.34675.


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.

Conclusion: 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.

MeSH terms

  • Animals
  • Antigens / adverse effects*
  • Antirheumatic Agents / therapeutic use
  • Arthralgia / drug therapy
  • Arthralgia / physiopathology*
  • Arthritis, Experimental / chemically induced*
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / physiopathology*
  • Biomechanical Phenomena / drug effects
  • Cells, Cultured
  • Disease Models, Animal
  • Female
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Hyperalgesia / physiopathology*
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1beta / pharmacology
  • Interleukin-1beta / physiology*
  • Knee Joint / drug effects
  • Knee Joint / physiopathology*
  • Rats
  • Rats, Inbred Lew
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / metabolism
  • TRPV Cation Channels / metabolism
  • Treatment Outcome


  • Antigens
  • Antirheumatic Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1beta
  • Receptors, Interleukin-1
  • TRPV Cation Channels
  • Trpv1 protein, rat