Nerves within the wall of the intestine may contribute to inflammatory responses, such as those occurring in
inflammatory bowel disease. Studies in an experimental model of
colitis have demonstrated that neuromodulation, through
chemical sympathectomy or administration of
lidocaine, can markedly attenuate granulocyte infiltration and tissue injury. Given the many pro-inflammatory effects of
substance P, we have evaluated the effects of a
tachykinin receptor (NK-1) antagonist,
RP 67580, in models of acute
colitis in the rat and guinea pig. While administration of
RP 67580 and a second NK-1 antagonist (CP-96,345-1) significantly reduced the infiltration of granulocytes into colonic tissue during the first 12 h after induction of
colitis in the rat, repeated administration of
RP 67580 over a three day period failed to significantly affect granulocyte recruitment or the severity of tissue injury. In contrast,
lidocaine enemas were effective in reducing both indices of
inflammation/injury. In the guinea pig, similar observations were made. These observations demonstrate that blockade of
NK-1 receptors over a three day period failed to significantly modify the course of experimental
colitis. It remains possible that the beneficial effects of
lidocaine may be due, in part, to inhibition of
substance P release, and that the contribution of
substance P to
inflammation in experimental
colitis occurs through
NK-1 receptor-independent mechanisms.