Substance P and CGRP do not play an important role in TNFα-induced inflammation

Previously,we have shown a role for TRPV1 in CFA-induced joint inflammation and suggested an involvement ofTNFα [1]. We have now investigated mechanisms involved in TNFα-induced inflammation in the mouse paw. The possible role of neuropeptides was investigated, since TRPV1 activation leads to CGRP and substance P release. NK₁ ^?/? and CGRP^?/? mice matched with their respective wild-types were used. Mice were given intraplantar injections ofTNF a (10pmol/50μl) and Tyrode (contralateral paw; 50μl). One group ofCG RP^-/-) mice were pretreated with the NK₁ receptor antagonist, SR140333 (480nmol/kg i.v.). Thermal hyperalgesic thresholds were measured using the Hargreaves technique before and over 4 hours after injection. Paw mass and neutrophil accumulation were measured. All the mice exhibited bilateral hyperalgesia, significant paw oedema and neutrophil accumulation in the TNFα-treated paw. These results suggest that substance P and CGRP are not important in development of hyperalgesia, oedema or neutrophil accumulation in this model.