Cellular and molecular basis of chronic constipation: Taking the functional/idiopathic label out

Abstract

In recent years, the improvement of technology and the increase in knowledge have shifted several strongly held paradigms. This is particularly true in gastroenterology, and specifically in the field of the so-called “functional” or “idiopathic” disease, where conditions thought for decades to be based mainly on alterations of visceral perception or aberrant psychosomatic mechanisms have, in fact, be reconducted to an organic basis (or, at the very least, have shown one or more demonstrable abnormalities). This is particularly true, for instance, for irritable bowel syndrome, the prototype entity of “functional” gastrointestinal disorders, where low-grade inflammation of both mucosa and myenteric plexus has been repeatedly demonstrated. Thus, researchers have also investigated other functional/idiopathic gastrointestinal disorders, and found that some organic ground is present, such as abnormal neurotransmission and myenteric plexitis in esophageal achalasia and mucosal immune activation and mild eosinophilia in functional dyspepsia. Here we show evidence, based on our own and other authors’ work, that chronic constipation has several abnormalities reconductable to alterations in the enteric nervous system, abnormalities mainly characterized by a constant decrease of enteric glial cells and interstitial cells of Cajal (and, sometimes, of enteric neurons). Thus, we feel that (at least some forms of) chronic constipation should no more be considered as a functional/idiopathic gastrointestinal disorder, but instead as a true enteric neuropathic abnormality.

Keywords: Constipation, Enteric glia, Enteric nervous system, Enteric neurons, Interstitial cells of Cajap, Neurogastroenterology

Core tip: Concerning gut motility, in the last years the basic/clinical interplay between gastroenterology and neurology has become stricter, and many pathologic conditions, among which constipation, related to abnormal gastrointestinal motility are now considered and studied by a neurogastroenterological point of view. However, the fact that these conditions are still labelled as “functional” or “idiopathic” is puzzling. We examined the evidence for taking these labels out from constipation, that should be considered as a true neurenteric dysfunction.