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.