A role of peptidergic nerves in the internal anal sphincter of Hirschsprung's disease

Background. It is not clear what contribution the internal anal sphincter m akes to the impaired motility observed in patients with Hirschsprung's dise ase (HD). Neuropeptides have recently been shown to be neurotransmitters in the nonadrenergic, noncholinergic inhibitory and excitatory nerves in the human gut. To clarify the physiologic significance of vasoactive intestinal polypeptide and substance P in the internal anal sphincter of HD (aganglio nosis), we investigated the enteric nerve responses on lesional and normal internal anal sphincter muscle strips above the dentate line. Methods. The lesional and normal internal anal sphincter muscle strips abov e the dentate line were derived from patients with HD (9 cases) and patient s who underwent rectal amputation for low rectal cancers (8 cases). A mecha nographic technique was used to evaluate in vitro muscle responses to these peptides of adrenergic and cholinergic nerves before and after treatment w ith various autonomic nerve blockers. Results. Nonadrenergic, noncholinergic inhibitory nerves were found to act on the normal internal anal sphincter but had no effect on the enteric nerv es in aganglionosis. Peptidergic (vasoactive intestinal polypeptide and sub stance P) nerves were found to act on normal colon, but no effect was obser ved in the aganglionic internal anal sphincter. Conclusions. These findings suggest that peptidergic nerves play an importa nt role in the impaired motility observed in the internal anal sphincter wi th HD.