DECREASED SUBSTANCE-P LEVELS IN RECTAL BIOPSIES FROM PATIENTS WITH SLOW TRANSIT CONSTIPATION

Objective: Previous studies in patients with chronic constipation foun d abnormalities in the nervous tissue of the large intestine, predomin antly in the muscularis externa. Since there is evidence that the nerv ous system of mucosa and submucosa is also involved in the control of colonic motility we investigated the contents of vasoactive intestinal polypeptide (VIP), somatostatin and substance P in rectal biopsies of patients with slow colonic transit constipation. Design and methods: Twenty-two patients (17 females, 5 males) with chronic slow transit co nstipation toro-anal transit with radio-opaque markers on high fibre d iet > 70 h) and long-term use of laxatives, and 20 controls (12 female s, 8 males) with no history of constipation, were included in this stu dy. Large rectal biopsy specimens including the submucosa were obtaine d from 5 cm above the dentate line and frozen in liquid nitrogen. Afte r microdissection of the biopsies into mucosa and submucosa the neurop eptides were extracted by boiling and homogenizing the tissue in aceti c acid and determined using validated radioimmunoassays. Results: Pati ents with slow transit constipation showed, compared to healthy contro ls, significantly lower levels of the excitatory neurotransmitter subs tance P in the mucosa and submucosa of rectal biopsies. There was no d ifference between the two groups concerning the levels of the inhibito ry neurotransmitters, VIP and somatostatin. Conclusion: Slow transit c onstipation is associated with abnormalities of the substance P conten t of the enteric nervous system of mucosa and submucosa. This seems no t to be related to chronic laxative use, since anthranoids cause a red uction in the levels of inhibitory neurotransmitters (VIP, somatostati n), but not of substance P, in the rat colon.