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The role of proinflammatory cytokines in the generation and maintenance of joint pain


Address for correspondence: Dr. Hans-Georg Schaible, Institute of Physiology/Neurophysiology, Universitätsklinikum Jena, Teichgraben 8, D-07740 Jena, Germany.


The proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) not only promote and maintain inflammation, they also contribute to the generation and maintenance of inflammatory pain by acting at nociceptive nerve cells. A large proportion of dorsal root ganglion (DRG) neurons express TNF receptors and receptor units for stimulation with IL-6. In the rat model of antigen-induced arthritis (AIA), neutralization of TNF-α by etanercept and infliximab reduced inflammation-evoked mechanical hyperalgesia at the inflamed knee joint. This treatment also attenuated the infiltration of macrophages into the DRGs usually observed during the acute phase of AIA. Intra-articular application of etanercept reduced the responses of C-fibers to mechanical stimulation of the inflamed joint but did not influence responses to stimulation of the normal joint. Finally, in cultured DRG neurons TNF-α increased the proportion of neurons that express the TRPV1 receptor and may thus contribute to the generation of inflammation-evoked thermal hyperalgesia.

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