MYENTERIC PLEXUS NEUROPATHY IN REFRACTORY FUNCTIONAL CHRONIC INTESTINAL CONSTIPATION

Abstract

Chronic functional constipation (CFC) is often attributed to behavioral factors, yet refractory cases increasingly show primary dysfunction of the enteric nervous system (ENS), particularly the myenteric plexus. This narrative review aimed to analyze the morphofunctional evidence linking myenteric plexus alterations to CFC and how this understanding underpins rational therapies. The search was conducted in PubMed/MEDLINE, Web of Science, EMBASE, and LILACS (2010–2024), using MeSH terms “Myenteric Plexus”, “Constipation”, and “Enteric Nervous System”. Included were full-thickness histological studies, colonic manometry, clinical trials with prokinetics, and expert reviews. Results show that patients with refractory CFC have a 30–60% reduction in nNOS⁺ inhibitory neurons, loss of interstitial cells of Cajal (ICCs), and hypoganglionosis—findings correlated with absent propagated contractions on manometry. Drugs such as prucalopride (5-HT₄ agonist) and linaclotide (guanylate cyclase-C agonist) act directly on the ENS, restoring the balance between contraction and relaxation. It is concluded that refractory CFC often reflects a myenteric plexus neuropathy with a demonstrable organic substrate, enabling more precise diagnosis and mechanism-based therapy.