Impact of chemotherapy-induced enteric nervous system toxicity on gastrointestinal mucositis

Curr Opin Support Palliat Care. 2020 Sep;14(3):293-300. doi: 10.1097/SPC.0000000000000515.

Abstract

Purpose of review: Chemotherapy is a first-line treatment for many cancers; however, its use is hampered by a long list of side-effects. Gastrointestinal mucositis is a common and debilitating side-effect of anticancer therapy contributing to dose reductions, delays and cessation of treatment, greatly impacting clinical outcomes. The underlying pathophysiology of gastrointestinal mucositis is complex and likely involves several overlapping inflammatory, secretory and neural mechanisms, yet research investigating the role of innervation in gastrointestinal mucositis is scarce. This review provides an overview of the current literature surrounding chemotherapy-induced enteric neurotoxicity and discusses its implications on gastrointestinal mucositis.

Recent findings: Damage to the intrinsic nervous system of the gastrointestinal tract, the enteric nervous system (ENS), occurs following chemotherapeutic administration, leading to altered gastrointestinal functions. Chemotherapeutic drugs have various mechanisms of actions on the ENS. Oxidative stress, direct toxicity and inflammation have been identified as mechanisms involved in chemotherapy-induced ENS damage. Enteric neuroprotection has proven to be beneficial to reduce gastrointestinal dysfunction in animal models of oxaliplatin-induced enteric neuropathy.

Summary: Understanding of the ENS role in chemotherapy-induced mucositis requires further investigation and might lead to the development of more effective therapeutic interventions for prevention and treatment of chemotherapy-induced gastrointestinal side-effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Cisplatin / adverse effects
  • Enteric Nervous System / drug effects*
  • Enteric Nervous System / physiopathology
  • Fluorouracil / adverse effects
  • Gastrointestinal Diseases / chemically induced*
  • Gastrointestinal Diseases / physiopathology
  • Gastrointestinal Diseases / prevention & control
  • Gastrointestinal Diseases / therapy
  • Humans
  • Inflammation / physiopathology
  • Irinotecan / adverse effects
  • Mucositis / chemically induced*
  • Mucositis / physiopathology
  • Mucositis / prevention & control
  • Mucositis / therapy
  • Oxaliplatin / adverse effects
  • Vincristine / adverse effects

Substances

  • Antineoplastic Agents
  • Oxaliplatin
  • Vincristine
  • Irinotecan
  • Cisplatin
  • Fluorouracil