Modulation of carrageenan-induced hind paw edema by substance P |
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Authors: | James P. Gilligan Susan J. Lovato Mark D. Erion Arco Y. Jeng |
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Affiliation: | (1) Unigene Laboratories, 07006 Fairfield, New Jersey;(2) Research Department, Pharmaceuticals Division, CIBA-GEIGY Corp., 07901 Summit, New Jersey;(3) Present address: Sandoz Pharmaceuticals, 07936 East Hanover, New Jersey;(4) Present address: Gensia, Inc., 92121 San Diego, California |
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Abstract: | Substance P has been implicated as a mediator of inflammation. The involvement 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 preceded 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 nonamidated precursor of substance P was coinjected with carrageenan. The effects of substance P depletion on inflammation were also evaluated. In animals pretreated with capsaicin followed by injection with carrageenan, 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 important 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. |
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