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Fundamentals of Neurogastroenterology Gut: First Published As 10.1136/Gut.45.2008.Ii6 on 1 September 1999

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Fundamentals of Neurogastroenterology Gut: First Published As 10.1136/Gut.45.2008.Ii6 on 1 September 1999 II6 Gut 1999;45(Suppl II):II6–II16 Fundamentals of neurogastroenterology Gut: first published as 10.1136/gut.45.2008.ii6 on 1 September 1999. Downloaded from J D Wood, D H Alpers, P L R Andrews Co-Chair, Committee on Basic Science: Brain–Gut, Multinational Working Teams to Develop Abstract Enteric innervation Diagnostic Criteria for Current concepts and basic principles of Neural networks for control of digestive Functional neurogastroenterology in relation to functions are positioned in the brain, spinal Gastrointestinal cord, prevertebral sympathetic ganglia, and in Disorders, functional gastrointestinal disorders are Departments of reviewed. Neurogastroenterology is em- the walls of the specialized organs that make up Physiology and phasized as a new and advancing subspe- the digestive system. Control involves an Internal Medicine, cialty of clinical gastroenterology and integrated hierarchy of neural centers. Starting The Ohio State digestive science. As such, it embraces at the level of the gut, fig 1 illustrates four lev- University College of els of integrative organization. Level 1 is the the investigative sciences dealing with Medicine and Public enteric nervous system (ENS), which has local Health, Columbus, functions, malfunctions, and malforma- circuitry for integrative functions independent Ohio, USA tions in the brain and spinal cord, and the JDWood of extrinsic nervous connections. The second sympathetic, parasympathetic and en- level of integration occurs in the prevertebral Co-Chair, Committee teric divisions of the autonomic innerva- sympathetic ganglia where peripheral reflex on Basic Science: tion of the digestive tract. Somatomotor pathways are influenced by preganglionic sym- Brain–Gut, systems are included insofar as pharyn- pathetic fibers from the spinal cord. Levels 3 Gastroenterology geal phases of swallowing and pelvic floor Division, Department and 4 are within the central nervous system of Medicine, involvement in defecation, continence, (CNS). At the third level, sympathetic and Washington University and pelvic pain are concerned. Inclusion parasympathetic outflow to the gut is deter- School of Medicine, St of basic physiology of smooth muscle, mined in part by reflexes with sensory fibers Louis, Missouri, USA mucosal epithelium, and the enteric that travel with autonomic nerves. The fourth D H Alpers immune system in the neurogastroen- level includes higher brain centers that supply Department of terologic domain relates to requirements descending signals that are integrated with Physiology, St Georges for compatibility with neural control incoming sensory signals at level 3. The neural Hospital Medical mechanisms. Psychologic and psychiatric networks at level 1 within the walls of the gut School, London, UK relations to functional gastrointestinal integrate contraction of the muscle coats, P L R Andrews disorders are included because they are transport across the mucosal lining and intramural blood flow into organized patterns Correspondence to: significant components of neurogastroen- Jackie D Wood, Ph.D, of behavior. These networks form the ENS, terology, especially in relation to projec- http://gut.bmj.com/ Professor of Physiology and which is considered to be one of the three sub- tions of discomfort and pain to the Internal Medicine, divisions of the autonomic nervous system Department of Physiology, digestive tract. together with sympathetic and parasympa- College of Medicine, The (Gut 1999;45(Suppl II):II6–II16) Ohio State University, 302 thetic divisions. Nervous malformations and Hamilton Hall, 1645 Neil malfunctions in these systems are increasingly Avenue, Columbus, Ohio Keywords: enteric nervous system; brain–gut axis; 43210, USA. Email: autonomic nervous system; nausea; gut motility; mast recognized as underlying factors in functional [email protected] cells; gastrointestinal pain; Rome II gastrointestinal disorders (FGID). The musculature, mucosal epithelium, and on September 30, 2021 by guest. Protected copyright. vasculature are the gut’s eVector systems. Higher brain centers Control level 4 Global behavior of the organ at any moment reflects neurally integrated activity of these sys- tems. The nervous system coordinates activity of the primary eVectors to produce meaningful Parasympathetic Sympathetic patterns of behavior for the whole organ. The system system Control level 3 ENS is a local minibrain within which is stored Prevertebral a library of programs for diVerent patterns of ganglia Control level 2 gut behavior. Digestive, interdigestive, and emetic patterns of intestinal behavior reflect outputs from three respective programs. For example, during emesis, propulsion in the Enteric nervous system Control level 1 upper small intestine is reversed for rapid movement of the contents toward the open pylorus and relaxed stomach. This program can be called up from the library either by Muscle/mucosa/vasculature Effector level Abbreviations used in this paper: CNS, central Figure 1 Neural control of the gut is hierarchic with four basic levels of integrative nervous system; ENS, enteric nervous system; FGID, organization. Level 1 is the enteric nervous system (ENS) which behaves like a local functional gastrointestinal disorder; NTS, nucleus minibrain. The second level of integrative organization is in the prevertebral sympathetic tractus solitarius; DVN, dorsal motor nucleus of the ganglia. The third and fourth levels are within the central nervous system (CNS). Sympathetic and parasympathetic signals to the digestive tract originate at level 3 and vagus; IBS, irritable bowel syndrome; ICC, interstitial represent the final common pathways for outflow of information from the CNS to the gut. cells of Cajal; 5-HT, 5-hydroxytryptamine; TRH The fourth level includes higher brain centers that provide input for integrative functions at thyrotropin releasing hormone; CRF, corticotropin level 3. releasing factor. Fundamentals of neurogastroenterology II7 the response in the wall of the intestine to dis- tension or mucosal stroking is a reflex contrac- Gut: first published as 10.1136/gut.45.2008.ii6 on 1 September 1999. Downloaded from tion of the circular muscle coat above the site of stimulation and inhibition of the circular mus- cle below the site. This pattern of behavior is Effector systems reproduced each time mechanoreceptors are activated by stretch of the wall or deformation Interneurons Muscle of the mucosa. This behavioral pattern, like Reflexes that of all reflexes, mirrors the output of a set of Sensory Motor Secretory fixed “hardwired” connections within the Program glands neurons library neurons interneuronal circuitry. Blood Pattern generators are neural networks that Information vessels processing generate rhythmic or repetitive behavior in eVector systems of animal phyla ranging from Integrated Integrated system invertebrates to higher vertebrates including synaptic circuits behavior humans. They are formed by interneuronal Figure 2 The conceptual model for the enteric nervous system (ENS) is the same as for synaptic connections that are preprogramed to the central nervous system (CNS). Sensory neurons, interneurons, and motor neurons are produce an adaptive pattern of eVector behav- connected synaptically for flow of information from sensory neurons to interneuronal integrative networks to motor neurons to eVector systems. The ENS organizes and ior. Pattern-generating circuitry consists of coordinates the activity of each eVector system into meaningful behavior of the integrated motor programs that signal motor neurons for organ. Bi-directional communication occurs between the CNS and ENS. control of repetitive cyclical behaviors. The commands from the brain or by local sensory sequence of events in stereotyped repetitions of detection of noxious substances in the lumen. motor outflow to the eVector system is Structure, function, and neurochemistry of determined by the program circuit. Pro- enteric ganglia diVer significantly from other grammed motor behavior, unlike reflex behav- autonomic ganglia. Unlike other autonomic ior, does not require sensory input to start the ganglia that function mainly as relay distribu- program, and feedback information from tion centers for signals transmitted from the sensory neurons is unnecessary for sequencing CNS, ENS ganglia are interconnected to form of the steps in the program. For many of the a nervous system with mechanisms for integra- behaviors generated by programmed motor tion and processing of information like those circuits (e.g., chewing, swallowing, breathing), found in the brain and spinal cord. On this the entire sequence of the motor program may basis, the ENS is sometimes referred to as the be initiated by input signals from a single neu- brain-in-the-gut or enteric minibrain. ron called a command neuron. Cyclic patterns Many properties of the ENS resemble the of secretory and contractile behavior seen in CNS12 and the conceptual model is the same the large intestine in response to histamine (fig 2). Like the CNS, the ENS works with release from enteric mast cells is an example of the output of pattern generating circuitry in the http://gut.bmj.com/ three functional categories of neurons identi- 34 fied as sensory, inter-, and motor neurons. ENS. Sensory neurons have receptor regions specialized for detecting changes in thermal, Central command signals chemical, or mechanical stimulus energy. The The vagus nerves have long been recognized as receptor regions transform changes in stimulus the major transmission pathway for control
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