Colonic neuropathological aspects in patients with intractable constipation due to obstructed defecation

Abstract

One of the most frequent subtypes of constipation is represented by obstructed defecation, and it has recently been reported that these patients may have colonic motor abnormalities in addition to alterations of the anorectal area. However, it is unknown whether these patients display abnormalities of the enteric nervous system, as reported in other groups of constipated subjects. For this reason, we evaluated the neuropathologic aspects of the enteric nervous system in a homogeneous group of patients with obstructed defecation. Colonic specimens from 11 patients (nine women, age range 39-66 years) undergoing surgery for symptoms refractory to any therapeutic measure, including biofeedback training, were obtained and examined by means of conventional histological methods and immunohistochemistry (NSE, S100, c-Kit, formamide-mAb, Bcl-2, CD34, alfa-actin). Analysis of the specimens showed that the enteric neurons were significantly decreased only in the submucosal plexus of patients (Po0.0001 vs controls), whereas the enteric glial cells of constipated patients were reduced in both the myenteric (P ¼ 0.018 vs controls) and the submucosal plexus (P ¼ 0.004 vs controls). No difference between patients and controls were found concerning c-Kit and CD34 expression, and the number of apoptotic neurons. These findings support the concept that at least a subgroup of patients with obstructed defecation and severe, intractable symptoms display abnormalities of the enteric nervous system, mostly related to the enteric glial cells. These findings might explain some of the pathophysiological abnormalities, and help to better understand this condition.

Pancolonic spatiotemporal mapping reveals regional deficiencies in, and disorganization of colonic propagating pressure waves in severe constipation

“…An intrinsic dysregulation is a stronger possibility. In constipated patients, a diminished density of interstitial cells of Cajal has been implicated, 32 as has a decrease in the overall population of glial cells 33 . Such defects could feasibly account for the striking truncation of propagation of PS and the spatiotemporal disorganization among consecutive PS 9 …”

An assessment of enteric nervous system and estroprogestinic receptors in obstructed defecation associated with rectal intussusception

“…Tissue samples were processed as previously described 28,31,38,39 . After removal, the surgical specimens were immediately fixed in 10% neutral‐buffered formalin for 24 h and transversal sections obtained.…”

“…It is, however, worth noting that, notwithstanding numerous studies present in literature on the various pathophysiologic aspects of OD, almost nil is known concerning its neuropathologic aspects, particularly the ENS. Although alterations of the neuroenteric circuitry have been postulated as a pathophysiologic ground for these patients, 29,30 only one study so far showed that a subgroup of patients with OD and severe, intractable symptoms display abnormalities of the ENS, 31 even though the analysis was done in segments proximal to the rectum.…”

Enteric glial cells: new players in gastrointestinal motility?

“…20 Moreover, we have found a significant decrease of EGC, but not ICC, in both the myenteric and submucosal plexuses of patients with severe constipation due to obstructed defecation refractory to treatment. 21 …”