Motility patterns in mouse colon: gastrointestinal dysfunction induced by anticancer chemotherapy

Colon cancer is a leading cause of cancer-related death in humans. 5-Fluorouracil (5-FU), a major chemotherapy treatment, has been used for decades to fight numerous types of cancers, including breast, colon, and head and neck carcinomas. Unfortunately, a large proportion of patients treated with 5-FU develop toxicities that include diarrhea, mucositis, neutropenia, and vomiting. While the side effects of 5-FU are well known, the mechanisms underlying the induction of these unpleasant symptoms are poorly understood. The study by McQuade etal. in this issue of Neurogastroenterology & Motility provides important new potential explanations for the gastrointestinal (GI) dysfunction induced by 5-FU. These researchers carefully investigated an overlooked research area in which the symptoms of GI-motility dysfunction maybe due to an effect on the enteric nervous system. McQuade etal. delivered 5-FU treatment to mice and discovered an initial increase in GI transit (associated with acute intestinal inflammation), followed by a slowing in transit. Major differences were noted in characteristics of colonic migrating motor complexes. These effects maybe causally related to deficits in enteric ganglia or neurotransmission. Their study identified specific neurochemical classes of neurons in the myenteric plexus most affected by 5-FU. This is the first study to provide evidence that the functional intrinsic neural pathways within the enteric nervous system are likely impaired by 5-FU, leading to colonic dysmotility. This review will describe major patterns of motor activity in isolated whole mouse colon and how these patterns are modified by anticancer chemotherapy.