Question: 

Persistent inflammatory processes such as rheumatoid arthritis generate chronic pain. The progression of inflammation involves proinflammatory cytokines such as Tumor-Necrosis-Factor a (TNFa) which is also capable to induce peripheral sensitization leading to hyperalgesia and pain-related behavior. But so far it is unclear whether TNFa is also involved in central sensitization during arthritis.

Methods: 

We performed in-vivo electrophysiology on nociceptive dorsal horn cells with knee joint input in the lumbar spinal cord in rats.

Results: 

TNFa application to the knee joint cavity as well as locally to the surface of the spinal cord elicited a moderate but significant increase of responses in these cells to mechanical stimulation of the leg. We investigated further the involvement of TNFa in spinal hyperexcitability evoked by knee joint inflammation using the TNFa-neutralizing compound Etanercept. When Etanercept was locally applied to the knee joint after established Kaolin/Carrageenan-induced joint inflammation (K/C), it reduced the responses to noxious knee stimulation. Spinal application of Etanercept attenuated but did not prevent the development of hyperexcitability following K/C. During early antigen-induced arthritis (AIA) at day 1, spinal application of Etanercept significantly reduced the responses of dorsal horn cells. Noteworthy, such an effect was not observed after prolonged AIA at day 3. On the molecular level, TNFa recruits the transcription factor NFkB at Ser536 probably through TNF-RI activation.

Conclusion: 

These data suggest that TNFa is involved in the early central sensitization of spinal cord neurons during the onset of joint inflammation but its role in the maintenance of spinal sensitization needs to be further explored.