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

Ann N Y Acad Sci. 2010 Apr:1193:60-9. doi: 10.1111/j.1749-6632.2009.05301.x.


The proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) 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-alpha 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-alpha increased the proportion of neurons that express the TRPV1 receptor and may thus contribute to the generation of inflammation-evoked thermal hyperalgesia.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthralgia / pathology*
  • Arthritis / pathology
  • Arthritis, Experimental / pathology
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Ganglia, Spinal / pathology
  • Hyperalgesia / pathology
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Knee Joint / pathology
  • Neurons, Afferent / pathology
  • Rats
  • TRPV Cation Channels / metabolism
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • Interleukin-6
  • TRPV Cation Channels
  • TRPV1 receptor
  • Tumor Necrosis Factor-alpha