Gastrointestinal Manifestations of Pediatric Autonomic Disorders $ Gisela Chelimsky, MD, * and Thomas C. Chelimsky, MD † Functional gastrointestinal disorders (FGIDs) are currently classified under the Rome criteria based on symptoms and absence of organic disease. Preliminary studies have shown that FGIDs are probably not restricted to the GI tract, but may represent a systemic disorder with comorbidities affecting other parts of the body, including migraine, fatigue, aches and pains, etc. The autonomic nervous system (ANS) provides the extrinsic control of GI motility, secretions, and even immune response. The role of the ANS in the development of FGIDs and comorbidities is still unclear. Limited data demonstrate orthostatic intolerance such as reflex syncope and postural tachycardia syndrome in a large subset of subjects with FGIDs. Some studies have found improvement in the GI symptoms with treatment of the orthostatic intolerance it produces. Prospective studies are needed to determine the chronology of the develop- ment of the comorbidities, the triggers that induce these syndromes, and effective treatments. This chapter aims to review current understanding of the role of the ANS in FGIDs. Semin Pediatr Neurol 20:27-30 C 2013 Published by Elsevier Inc. F unctional gastrointestinal disorders (FGIDs) have now been carefully classified into adult and pediatric disorders through the Rome criteria, currently in their third iteration. 1 Traditionally, these disorders required the absence of organic findings, a definition that is now nearly obsolete, based on recent discoveries in irritable bowel syndrome (IBS) and other FGIDs. Current understanding is based on the biopsychological model 1 comprising an interaction of (1) early life events, (2) psychological con- ditions, and (3) physiological factors that interrelate through the central nervous system, the autonomic ner- vous system (ANS), and the enteric nervous system. The enteric nervous system is sometimes considered as the third branch of the ANS, or sometimes as the ‘‘second brain’’, because of its large number of neurons (more than the spinal cord). The ANS can respond to signals from the gut ascending to higher central regions, or by descending pathways modulated by emotions or cognitive needs. 2 The brain is continuously informed by afferent nerves about the gut activities and state, and the gut receives efferent input modulated by stress and emotions. The bidirectional information is not limited just to motility and digestion but also to the inflammatory response, 3 and probably to many other parameters of gut functioning currently under study such as permeability and microbiome composition, and others that have yet to be established. FGIDs include many disorders, such as IBS, functional dyspepsia, functional abdominal pain, functional abdom- inal pain syndrome, cyclic vomiting syndrome (CVS), etc. The etiopathogenesis of these disorders remains unknown, though some progress has occurred in IBS, based on the observation that it may follow an acute gastroenteritis. A low-grade inflammatory response occurs, characterized by mast cell activation and increased lymphocytic and enterochromaffin cell infiltra- tion. This mast cell activation may play a role in the sensitization of nociceptive fibers. 3 Studies in adults with IBS have also shown dysregulation of the ANS. 4,5 Afferent and Efferent Autonomic Fibers to the GI Tract The parasympathetic innervation to the GI tract is received through the vagus nerve for the foregut, and by the sacral nerves to the distal intestine. 2 The vagus nerve innervates the stomach, the small intestine, and the proximal colon. It 1071-9091/11/$-see front matter & 2013 Published by Elsevier Inc. 27 http://dx.doi.org/10.1016/j.spen.2013.01.002 $ Financial disclosure: None, except NIH RO1 funding (for both). *Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI. †Department of Neurology, Medical College of Wisconsin, Milwaukee, WI. Address reprint requests to Gisela Chelimsky, MD, Medical College of Wisconsin, Division of Pediatric Gastroenterology, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail: gchelimsky@mcw.edu