title: Neuroanatomy of lower gastrointestinal pain disorders.
abstract: Chronic abdominal pain accompanying intestinal inflammation emerges from the hyperresponsiveness of neuronal, immune and endocrine signaling pathways within the intestines, the peripheral and the central nervous system. In this article we review how the sensory nerve information from the healthy and the hypersensitive bowel is encoded and conveyed to the brain. The gut milieu is continuously monitored by intrinsic enteric afferents, and an extrinsic nervous network comprising vagal, pelvic and splanchnic afferents. The extrinsic afferents convey gut stimuli to second order neurons within the superficial spinal cord layers. These neurons cross the white commissure and ascend in the anterolateral quadrant and in the ipsilateral dorsal column of the dorsal horn to higher brain centers, mostly subserving regulatory functions. Within the supraspinal regions and the brainstem, pathways descend to modulate the sensory input. Because of this multiple level control, only a small proportion of gut signals actually reaches the level of consciousness to induce sensation or pain. In inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) patients, however, long-term neuroplastic changes have occurred in the brain-gut axis which results in chronic abdominal pain. This sensitization may be driven on the one hand by peripheral mechanisms within the intestinal wall which encompasses an interplay between immunocytes, enterochromaffin cells, resident macrophages, neurons and smooth muscles. On the other hand, neuronal synaptic changes along with increased neurotransmitter release in the spinal cord and brain leads to a state of central wind-up. Also life factors such as but not limited to inflammation and stress contribute to hypersensitivity. All together, the degree to which each of these mechanisms contribute to hypersensitivity in IBD and IBS might be disease- and even patient-dependent. Mapping of sensitization throughout animal and human studies may significantly improve our understanding of sensitization in IBD and IBS. On the long run, this knowledge can be put forward in potential therapeutic targets for abdominal pain in these conditions.
authors.affiliation: Wim Vermeulen, Joris G De Man, Paul A Pelckmans, Benedicte Y De Winter, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Vermeulen
authors.affiliation: Wim Vermeulen, Joris G De Man, Paul A Pelckmans, Benedicte Y De Winter, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Joris G
authors.initials: JG
authors.lastname: De Man
authors.affiliation: Wim Vermeulen, Joris G De Man, Paul A Pelckmans, Benedicte Y De Winter, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Pelckmans
authors.affiliation: Wim Vermeulen, Joris G De Man, Paul A Pelckmans, Benedicte Y De Winter, Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
authors.forename: Benedicte Y
authors.initials: BY
authors.lastname: De Winter
mesh_terms: D015746:Abdominal Pain / Q000473:pathology / Q000503:physiopathology*; D000344:Afferent Pathways / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D017615:Enteric Nervous System / Q000473:pathology / Q000503:physiopathology*; D041981:Gastrointestinal Tract / Q000294:innervation*; D006801:Humans; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology*; D015212:Inflammatory Bowel Diseases / Q000473:pathology / Q000503:physiopathology*; D043183:Irritable Bowel Syndrome / Q000473:pathology / Q000503:physiopathology*; D058748:Pain Perception; D017288:Pain Threshold
keywords: Afferent nerves; Chronic pain; Inflammatory bowel disease; Irritable bowel syndrome; Sensitisation; Sensory nerves; Visceral hypersensitivity