Journal Article

Neuroplasticity and dysfunction after gastrointestinal inflammation

Linden, David R., Brierley, Stuart M.

2014

Overview

Key Points Gastrointestinal infection and inflammation are key risk factors for the development of numerous clinical gastrointestinal disorders that present with symptoms such as altered motility or secretion, abdominal discomfort and pain Neuronal processing along the gut–brain axis is crucial for the function and modulation of key gastrointestinal processes; findings suggest that this processing can be altered by gut inflammation or infection Inflammation or infection causes specific changes in enteric neuronal excitability, which can persist after inflammation has resolved; in some experimental models, inflammation also causes a rapid loss of myenteric neurons and viscerofugal neurons Inflammation causes a specific hypersensitivity of visceromotor sympathetic neurons in prevertebral ganglia, which persists long after inflammation has resolved Extrinsic gut sensory afferents express pronociceptive channels and receptors that can be activated in response to inflammatory and immune mediators, leading to acute neuronal hyperexcitability, visceral hypersensitivity and neurogenic inflammation Inflammation causes lowering of mechanical activation thresholds of high-threshold or low-threshold afferents, which leads to hyperexcitability in afferent neuronal cell bodies, and increased activation of nociceptive pathways in the central nervous system Neuronal processing along the gut–brain axis is crucial for the function and modulation of key gastrointestinal processes, and evidence suggests that this processing can be altered by gut inflammation or infection. This Review discusses the current body of evidence for neuroplasticity (the structural, synaptic or intrinsic changes that alter neuronal function) affecting gastrointestinal function. The gastrointestinal tract is innervated by several distinct populations of neurons, whose cell bodies either reside within (intrinsic) or outside (extrinsic) the gastrointestinal wall. Normally, most individuals are unaware of the continuous, complicated functions of these neurons. However, for patients with gastrointestinal disorders, such as IBD and IBS, altered gastrointestinal motility, discomfort and pain are common, debilitating symptoms. Although bouts of intestinal inflammation underlie the symptoms associated with IBD, increasing preclinical and clinical evidence indicates that infection and inflammation are also key risk factors for the development of other gastrointestinal disorders. Notably, a strong correlation exists between prior exposure to gut infection and symptom occurrence in IBS. This Review discusses the evidence for neuroplasticity (structural, synaptic or intrinsic changes that alter neuronal function) affecting gastrointestinal function. Such changes are evident during inflammation and, in many cases, long after healing of the damaged tissues, when the nervous system fails to reset back to normal. Neuroplasticity within distinct populations of neurons has a fundamental role in the aberrant motility, secretion and sensation associated with common clinical gastrointestinal disorders. To find appropriate therapeutic treatments for these disorders, the extent and time course of neuroplasticity must be fully appreciated.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/308/575 / 692/698/1688/1315/1951 / 692/699/1503/1581/2071 / 692/699/249/2510/257 / Animals / Biomedicine / Enteric Nervous System - immunology / Enteric Nervous System - physiopathology / Gastroenterology / Gastrointestinal diseases / Gastrointestinal Diseases - immunology / Gastrointestinal Diseases - physiopathology / Gastrointestinal Motility / Gastrointestinal system / Gastrointestinal Tract - immunology / Gastrointestinal Tract - innervation / Gastrointestinal Tract - physiopathology / Hepatology / Humans / Inflammation / Inflammatory Bowel Diseases - immunology / Inflammatory Bowel Diseases - physiopathology / Irritable Bowel Syndrome - immunology / Irritable Bowel Syndrome - physiopathology / Medical examination / Medicine & Public Health / Neuronal Plasticity - immunology / Neuronal Plasticity - physiology / Neurons / Neuroplasticity / Patient outcomes / Physiological aspects / review-article