Functional neuromuscular impairment in severe intestinal dysmotility.

Abstract

Chronic intestinal pseudo-obstruction (CIPO) and enteric dysmotility (ED) are severe intestinal motility disorders usually associated with underlying neuromuscular abnormalities. To evaluate the in vitro neuromuscular function of patients with severe intestinal motility disorders. Full-thickness intestinal biopsies (16 jejunum and 3 ileum) obtained from patients with CIPO (n=10) and ED (n=9) were studied using muscle bath and microelectrode techniques. Control samples (n=6 ileum and n=6 jejunum) were used to establish the range of normality. Fourteen parameters were defined to assess muscle contractility and nerve-muscle interaction: five to evaluate smooth muscle and interstitial cells of Cajal (ICC) and nine to evaluate inhibitory neuromuscular transmission. For each sample, a parameter was scored 0 if the value was inside the normal range or a value of 1 if it was outside. Patients' samples (CIPO/ED) had more abnormal parameters than controls (P<0.001 for both jejunum and ileum). Functional abnormalities were found to be heterogeneous. The most prevalent abnormality was a decreased purinergic neuromuscular transmission, which was detected in 43.8% of jejunal samples. Abnormalities of neuromuscular intestinal function are detected in vitro in severe intestinal dysmotility. However, consistent with the heterogeneity of the disease pathophysiology, functional impairment cannot be attributed to a single mechanism. Specifically, defects of purinergic neuromuscular transmission may have an important role in motility disorders of the gastrointestinal tract.