The role of interleukin-1β in arthritic pain: Main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis
Article first published online: 28 NOV 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 12, pages 3897–3907, December 2012
How to Cite
Ebbinghaus, M., Uhlig, B., Richter, F., von Banchet, G. S., Gajda, M., Bräuer, R. and Schaible, H.-G. (2012), The role of interleukin-1β in arthritic pain: Main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis. Arthritis & Rheumatism, 64: 3897–3907. doi: 10.1002/art.34675
- Issue published online: 28 NOV 2012
- Article first published online: 28 NOV 2012
- Accepted manuscript online: 29 AUG 2012 03:07PM EST
- Manuscript Accepted: 9 AUG 2012
- Manuscript Received: 16 FEB 2012
- BMBF (Immunopain program)
- DFG. Grant Number: Scha 404/13-2
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.
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.
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.
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.