Inhibition of carrageenan induced inflammation in the rat knee joint by substance P antagonist.
The pathophysiology of acute joint inflammation remains unclear. Evidence is available to suggest a neurally mediated component to the inflammatory process. Acute joint inflammation in the rat knee, induced by intra-articular injection of 2% carrageenan, was reduced by 44% in animals whose knee had previously been injected with 1% capsaicin, while chronic joint denervation produced a 37% reduction. These results indicate a significant neurogenic component in this model of acute joint inflammation. Substance P may be the mediator of this response as intra-articular injection of this agent provoked an acute inflammatory response. Pretreatment of the test knee with the substance P antagonist d-Pro4,d-Trp7 9 10-SP(4-11), however, resulted in a 93% reduction of the inflammatory response to carrageenan. This unexpectedly large effect suggests that this substance P antagonist blocks both neurogenic and non-neurogenic mediators of inflammation. Sympathetic efferent fibres innervating the knee joint were not found to contribute to the neurogenic component of the inflammatory process.
Lam
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Institute of Physiology, University of Glasgow.
Ferrell
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WR
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002351:Carrageenan / Q000276:immunology*; D006614:Hindlimb; D007249:Inflammation / Q000276:immunology; D007596:Joints / Q000276:immunology*; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013585:Synovitis / Q000276:immunology*
D010446:Peptide Fragments; D013373:Substance P; C040436:substance P (4-11), Pro(4)-Trp(7,9,10)-; D002351:Carrageenan; D002211:Capsaicin