Osteoarthritis joint pain: the cytokine connection

Abstract

Osteoarthritis is a chronic and painful disease of synovial joints. Chondrocytes, synovial cells and other cells in the joint can express and respond to cytokines and chemokines, and all of these molecules can also be detected in synovial fluid of patients with osteoarthritis. The presence of inflammatory cytokines in the osteoarthritic joint raises the question whether they may directly participate in pain generation by acting on innervating joint nociceptors. Here, we first provide a systematic discussion of the known proalgesic effects of cytokines and chemokines that have been detected in osteoarthritic joints, including TNF-α, IL-1, IL-6, IL-15, IL-10, and the chemokines, MCP-1 and fractalkine. Subsequently, we discuss what is known about their contribution to joint pain based on studies in animal models. Finally, we briefly discuss limited data available from clinical studies in human osteoarthritis.

Keywords: Animal models; Chemokines; Cytokines; Osteoarthritis; Pain.

Figure 1

Nociceptors (medium-sized myelinated Aδ fibers and small unmyelinated C-fibers) detect noxious signals in the innervated tissues and carry them to the dorsal horn of the spinal cord. The cell bodies of these pseudounipolar nociceptors are located in the dorsal root ganglia (DRG) and extend axons to the periphery as well as centrally to the dorsal horn, where the first synapse occurs. In osteoarthritis, all joint tissues participate in driving progressive structural joint damage, including the articular cartilage, subchondral bone, and the synovial membrane. Ongoing chronic tissue damage and low-level inflammation generates cytokines and chemokines that may directly act on innervating nociceptors. The precise nature of this interaction in the arthritic joint has not been elucidated Osteoarthritis is a chronic and painful disease of synovial joints. Osteoarthritic joint tissues produce and respond to cytokines and chemokines. Cytokines promote joint destruction and directly activate innervating nociceptors.