Relevance of tumour necrosis factor-alpha for the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw.

1. The present study evaluated the participation of tumour necrosis factor-alpha (TNF-alpha) in the inflammatory and nociceptive responses evoked by carrageenan in the mouse paw. 2. The intraplantar injection of carrageenan (300 microg paw-1) induced a marked and biphasic paw oedema formation (peaks at 6 and 72 h), which was accompanied by a long-lasting mechanical allodynia (that remained elevated for up to 72 h) and a significant increase of myeloperoxidase (MPO) activity (peak at 6 h) in both Swiss and C57/BL6 mice. 3. The paw oedema, the elevation of MPO activity and to a lesser extent the mechanical allodynia elicited by carrageenan were found to be significantly reduced in TNF-alpha p55 receptor knockout mice. 4. Of interest, the systemic administration of an anti-TNF-alpha antibody produced a significant inhibition of paw oedema, mechanical allodynia and MPO activity. A noteworthy decrease in inflammatory and nociceptive responses caused by carrageenan was also observed when mice were previously treated with the preferential inhibitor of TNF-alpha synthesis, thalidomide. 5. The present results clearly indicate that the proinflammatory cytokine TNF-alpha plays a critical role in the oedema formation, as well as in the mechanical allodynia and the neutrophil migration, following carrageenan administration into the mouse paw. Intraplantar injection of carrageenan in mice could constitute a useful model for assessment of the in vivo effects of potential inhibitors of TNF-alpha-related pathways.