Neuronal anomalies and normal muscle morphology at the hypomotile ileocecocolonic region of patients affected by idiopathic chronic constipation

Patients suffering from idiopathic slow-transit chronic constipation have a delayed colonic transit referable to a decrease or loss of propagating con tractions. Myogenic and/or neural mechanisms have been implicated in the pa thophysiology of this dysfunction and neuronal abnormalities have been desc ribed at the ascending, descending and sigmoid colon. The morphology and mo tile behaviour of the ileocecocolonic region, which in healthy subjects reg ulates cecum filling and emptying, have never been investigated in such dis ease. Therefore, we endoscopically ascertained whether a motility impairmen t was present at these junctional areas and neither spontaneous nor provoke d occlusive contractions were found at the cecocolonic junction. Light and electron microscope examination of the entire colon revealed apparently nor mal features of neurons, smooth muscle cells and interstitial cells of Caja l, while immunohistochemistry and quantitative analysis demonstrated neuron al anomalies at the junctional areas. These anomalies consisted of low tota l neuron density and significantly few VIP-immunoreactive neurons at the tw o enteric plexuses, significantly few NOS-immunoreactive neurons at the mye nteric plexus and significantly more NOS-immunoreactive neurons at the subm ucous plexus. These findings exclude a myopathy and demonstrate the existen ce of a neuropathy. In particular, the presence at the ileocecocolonic regi on of few VIP- and NO-producing neurons suggests that there might be a redu ced VIP and NO production which may result in a compromised relaxation and/ or onset of propagating contractions, slowing down bolus transit. The prese nce at the proximal colon of such an abnormality might explain why left col ectomy and/or cecorectal anastomosis are unsuccessful in patients with this disease.