Possible involvement of the spinal substance P system in pilocarpine-induced scratching in mice

Abstract

IT administration of pilocarpine in the spinal subarachnoid space of mice produced a dose-related hindlimb scratching. When coadministered with substance P IT, the pilocarpine-induced scratches were enhanced by high doses of substance P but not by subthreshold doses. This characteristic behavioral response was inhibited dose dependently by IT coadministration of spantide [ D-Arg 1, D-Trp 7,9, Leu 11] substance P. Significant antagonistic effects of [ D-Phe 7, D-His 9] substance P (6–11), a selective antagonist for substance P receptors, and substance P (1–7), a substance P N-terminal fragment, were observed against the pilocarpine-induced scratching. Pretreatment with substance P antiserum resulted in the reduction of the response to pilocarpine. When coadministered IT with pilocarpine, atropine potently inhibited pilocarpine-induced scratching. These results demonstrate that not only muscarinic receptors but also substance P-containing neurons in the mouse spinal cord may be involved in elicitation of the scratching behavior following IT injection of pilocarpine.