Clinical and experimental evidence of sympathetic neural dysfunction during inflammatory bowel disease.
1. Inflammatory bowel diseases (IBD) alter the function of the enteric nervous system and the sensory innervation of the gastrointestinal (GI) tract. Less is known about whether IBD also affects the sympathetic nervous system (SNS). Given the importance of the SNS in regulating GI function and possibly immune system activation, the present review examines the evidence of sympathetic dysfunction during IBD and its possible consequences. 2. Sympathetic axons within the GI tract innervate several cell types, including vascular myocytes, enteric neurons and immune cells. The major neurotransmitters released from sympathetic varicosities are noradrenaline, neuropeptide Y and ATP or a related purine. 3. Clinical studies of IBD patients have provided evidence of an association between IBD and axonal or demyelinating neuropathy. Assays of autonomic function suggest that ulcerative colitis and Crohn's disease, the two major forms of IBD, have contrasting effects on sympathetic neural activity. 4. Animal models of IBD have been used to examine the effects of these diseases on sympathetic neurophysiology. A decrease in the release of noradrenaline from sympathetic varicosities in inflamed and uninflamed regions of the GI tract has consistently been reported. Recent findings suggest that the decrease in neurotransmitter release may be due to inhibition of N-type voltage-gated Ca(2+) current in post-ganglionic sympathetic neurons. 5. Interest in the role of the SNS in IBD is rapidly increasing. However, much work needs to be done to enhance understanding of how SNS function is altered during IBD and what contribution, if any, these changes make to pathogenesis.
Boissé
Lysa
L
Division of Neurology, Gastrointestinal Diseases Research Unit, Queen's University, Kingston, Ontario, Canada.
Chisholm
Susan P
SP
Lukewich
Mark K
MK
Lomax
Alan E
AE
D000818:Animals; D001342:Autonomic Nervous System Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D015212:Inflammatory Bowel Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D007422:Intestines / Q000276:immunology / Q000473:pathology; D008954:Models, Biological; D013564:Sympathetic Nervous System / Q000473:pathology / Q000503:physiopathology*