Neurogastroenterology

K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released July 12, 2000; last updated July 23, 2016; expires July 23, 2019

Overview

Neurogastroenterology is a subspecialty of gastroenterology that overlaps with neurology. The enteric nervous system is a collection of neurones that can function more or less independently of the central nervous system (CNS). This article discusses the neurologic manifestations of gastroenterological disorders as well as significant gastroenterological manifestations of neurologic disorders. The CNS plays a role in the pathogenesis of some gastrointestinal disorders. Management depends on the individual disorder. Some general approaches to treatment of various gastrointestinal manifestations of neurologic disease are outlined in this article. Among the specialized procedures in development, transplantation of neural stem cells is a promising therapeutic approach for disorders of the enteric nervous system.

Key points

 

• Neurogastroenterology covers primarily the diseases of the intrinsic enteric nervous system of the gastrointestinal tract.

 

• Several neurologic disorders have gastroenteric manifestations.

 

• Similarly gastrointestinal disorders can lead to neurologic complications.

 

• Knowledge of the pathomechanism and management of neurogastroenterological disorders is important for the practice of neurology.

Historical note and terminology

Neurogastroenterology is defined as neurology of the gastrointestinal tract, liver, gallbladder, and pancreas and encompasses control of digestion through the enteric nervous system, the central nervous system, and integrative centers in sympathetic ganglia (Furness 2012). Neurogastroenterology has evolved as a subspecialty of gastroenterology during the past decade. It deals with diseases in which a disordered interaction takes place between the nervous system and the gastrointestinal system. Neurogastroenterology covers primarily the diseases of the intrinsic enteric nervous system, a part of the nervous system that evolved more than 500 million years ago and contains about 100 million neurons in humans, which constitute the "brain of the gut." This system controls the motility, endocrine secretions, and microcirculation of the gastrointestinal system (Goyal and Hirano 1996). Normal motility and transit through the gastrointestinal system result from a balanced interaction between the enteric nervous system and the extrinsic autonomic nervous system. Disorders of the autonomic nervous system that affect the gastrointestinal system usually manifest as disturbances of motility. Several gastrointestinal disorders including chronic intestinal pseudo-obstruction were once considered functional disorders but are now recognized as organic disorders because the pathology of the enteric nervous system has been identified (Mathias and Clench 1995). The term "functional gastrointestinal disorders" is applied to those disorders in which no abnormal metabolic or physical processes that could account for the symptoms can be identified, for example, irritable bowel syndrome (Drossman 2006). Emerging concepts in neurogastroenterology implicate dysfunctions at the levels of the enteric and central nervous systems as underlying causes of the prominent symptoms of many functional gastrointestinal disorders (Wood 2007). A consideration of psychological and psychiatric aspects of these disorders is important because they are significant in relation to projections of discomfort and pain in the digestive tract as well as stress-induced gastrointestinal disorders. Neurogastroenterological disorders include gastrointestinal manifestations of well-known neurologic disorders as well as primary disorders of the gastrointestinal system that lead to neurologic manifestations.

The relationship between the brain and the gut has been known for a long time. In the 19th century, Beumont made the observation in subjects with gastric fistulae that fear and anger and other disturbances of the nervous system led to suppression of gastric secretion and delay in emptying of the stomach (Beumont 1833). Stress-induced changes in intestinal motility have been recognized since 1902 when Cannon, the discoverer of barium meal technique for studying gastrointestinal motility, noted changes in the flow of intestinal contents in cats confronted by growling dogs (Cannon 1902). Although congenital megacolon was described by Hirschsprung in 1888, the fact that dilatation is secondary to the absence of submucosal Meissner and myenteric Auerbach plexuses was not established until 60 years later. Parkinson described dysphagia and constipation as cardinal features of Parkinson disease (Parkinson 1817). Although clinical neurologists in the 19th and 20th century recognized the relationship between the gastrointestinal system and neurologic disorders, there was a paucity of basic research on identifying the basic mechanisms involved in the transfer of information between the gut and the brain. Studies starting in the 1940s and 1950s described neurologic disorders secondary to gastrointestinal disorders. These were mainly nutritional deficiency disorders of the CNS, and the first book on this topic was published in 1974 (Pallis and Lewis 1974).

A landmark study in 1977 showed that intracerebroventricular injection of a hypothalamic peptide, thyrotropin releasing hormone, stimulates colonic motility in the anesthetized rabbit (Smith et al 1977). Several brain structures regulating gastrointestinal function were identified by electrophysiological techniques in the 1980s. The nucleus tractus solitarius was found to be the major projection target of vagal afferent fibers and, in turn, projected to the dorsal motor nucleus of the vagus, a major origin of efferent vagal fibers. Vagal afferent stimulation-evoked gastric secretion was shown to be suppressed by paraventricular hypothalamic nucleus lesion (Rogers and Hermann 1985).

It is well recognized that the enteric nervous system is a collection of neurones that can function more or less independently of the central nervous system and controls or modulates motility, exocrine and endocrine secretions, and microcirculation, immune, and inflammatory processes. The enteric nervous system is sometimes called the “second brain” because of the diversity of neuronal cell types and complex, integrated circuits that permit it to autonomously regulate many processes in the bowel (Avetisyan et al 2015). The gut and the brain are highly integrated. Animal experimental studies have shown that changes in gut microbiota can alter signaling mechanisms, emotional behavior, and visceral nociceptive reflexes. A study in healthy women has shown that consumption of a fermented milk product with probiotic affects activity of brain regions that control central processing of emotion and sensation (Tillisch et al 2013). Understanding the neural regulation of gut function and sensation makes it easier to understand the interrelatedness of emotionality, symptom-attentive behavior or hypervigilance, and pain.

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