MODULATION OF CARRAGEENAN-INDUCED HIND PAW EDEMA BY SUBSTANCE-P

Substance P has been implicated as a mediator of inflammation. The inv olvement of this neuropeptide in carrageenan-induced hind paw edema in the rat was assessed. Subcutaneous injection of carrageenan into the rat paw caused a significant increase in substance P levels, which pre ceded the onset of inflammation. While injection of substance P alone caused mild edema, coadministration of submaximal doses of carrageenan and substance P resulted in a synergistic exacerbation in the degree of inflammation. This synergistic response was not detected when the n onamidated precursor of substance P was coinjected with carrageenan. T he effects of substance P depletion on inflammation were also evaluate d. In animals pretreated with capsaicin followed by injection with car rageenan, no significant increase in either the levels of substance P or the extent of edema was observed when compared to capsaicin-treated controls. These results indicate that substance P may play an importa nt role in the early stages of carrageenan-induced paw edema and that a reduction in the biosynthesis of substance P may lessen the severity of this inflammatory response.