Modulation of carrageenan-induced hind paw edema by substance P.
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.
Gilligan
J P
JP
Unigene Laboratories, Fairfield, New Jersey 07006.
Lovato
S J
SJ
Erion
M D
MD
Jeng
A Y
AY
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004487:Edema / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D005260:Female; D005528:Foot / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*
D013373:Substance P; D002351:Carrageenan; D002211:Capsaicin