The tachykinin NK1 receptor antagonist SR140333 prevents the increase of nerve growth factor in rat paw skin induced by substance P or neurogenic inflammation

Abstract Target-derived nerve growth factor provides trophic support for adult primary afferent neurons containing calcitonin gene-related peptide and tachykinins. Noxious chemical or thermal stimuli cause the release of these mediators from peripheral afferent nerve endings. However, little is known of the extent to which these mediators, in turn, influence nerve growth factor expression in the innervated tissue. The aim of this study was therefore to investigate the possible effect of exogenous substance P, or neurogenic inflammation on the nerve growth factor concentration in the skin of the rat hindpaw. Our results show that substance P as well as topical application of mustard oil cause a significant increase in detectable nerve growth factor, an effect that was prevented by treatment of rats with the tachykinin NK 1 receptor antagonist SR140333. We did not observe a significant inhibitory effect of SR140333 on the nerve growth factor content in non-treated skin, or the nerve growth factor increase caused by carrageenan or allergic inflammation. The results provide evidence that substance P as well as neurogenic inflammation cause a rapid increase in detectable nerve growth factor in the paw skin and suggest the involvement of NK 1 receptors in this effect. We obtained no evidence for the participation of a NK 1 receptor-mediated nerve growth factor increase in models of inflammation induced by non-neurogenic stimuli.