The role of interleukin-1? in arthritic pain: main involvement in thermal, but not mechanical, hyperalgesia in rat antigen-induced arthritis.
Arthritis Rheum. 2012 Dec;64(12):3897-907
Authors: Ebbinghaus M, Uhlig B, Richter F, von Banchet GS, Gajda M, Bräuer R, Schaible HG
OBJECTIVE: Interleukin-1? (IL-1?) 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-1? 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-1? 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-1? 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-1? 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-1? increased the mechanosensitivity of C-fibers of the joint, but reduced the mechanosensitivity of A?-fibers, thus having opposite effects on these mechanonociceptive nerve fibers.
CONCLUSION: In the context of arthritic knee pain, IL-1? and IL-1 receptors appear to be involved in thermal, rather than mechanical, hyperalgesia. Therefore, neutralization of IL-1? may be mainly antinociceptive in disease states characterized by thermal hyperalgesia, but not in disease states mainly characterized by mechanical hyperalgesia.
PMID: 22933159 [PubMed – in process]