The autonomic nervous system and inflammatory bowel disease

Crohn's disease and ulcerative colitis, collectively known as inflammatory bowel disease (IBD), are chronic, recurring, inflammatory conditions of the intestine. The precise mechanisms underlying the pathogenesis of IBD are not yet clear but they are believed to involve a number of precipitating factors, most notably genetic susceptibility and environmental influences. The autonomic nervous system (ANS) has long been known as a critical regulator of intestinal function and much evidence now exists to suggest that it also plays an important role in the development of IBD. Dramatic changes in the ANS in IBD are apparent from the cellular to the molecular level ultimately leading to altered communication between the ANS and effector cells of the intestine. This review aims to synthesize the current understanding of the pathogenesis of IBD with a particular emphasis on the role that the ANS plays in the progression of these diseases.

[1]  G. Burnstock,et al.  Neurochemical coding in the small intestine of patients with Crohn's disease. , 1997, Gut.

[2]  D. Hollander Inflammatory bowel diseases and brain-gut axis. , 2003, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[3]  H. Friess,et al.  Nerve growth factor and Trk high affinity receptor (TrkA) gene expression in inflammatory bowel disease , 2000, Gut.

[4]  J. Macdonald,et al.  Transdermal nicotine for induction of remission in ulcerative colitis. , 2004, The Cochrane database of systematic reviews.

[5]  M. D'Andrea,et al.  Vanilloid receptor 1 antagonists attenuate disease severity in dextran sulphate sodium‐induced colitis in mice , 2004, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[6]  K. Sharkey,et al.  Plasticity of the enteric nervous system during intestinal inflammation , 2005, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[7]  H. Mizukami,et al.  Adeno-associated virus 2 co-receptors? , 1999, Nature Medicine.

[8]  R. Stead,et al.  Vagal afferent nerve fibres contact mast cells in rat small intestinal mucosa. , 1997, Neuroimmunomodulation.

[9]  J. Galmiche,et al.  Changes in chemical coding of myenteric neurones in ulcerative colitis , 2003, Gut.

[10]  J. Wood,et al.  Enteric neuroimmunophysiology and pathophysiology. , 2004, Gastroenterology.

[11]  K. Jacobson,et al.  Myenteric plexus injury and apoptosis in experimental colitis , 2005, Autonomic Neuroscience.

[12]  W. Stremmel,et al.  IL‐1β and IL‐10 have dual effects on enteric glial cell proliferation , 2001, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[13]  P. Rutgeerts,et al.  Current status of genetics research in inflammatory bowel disease , 2005, Genes and Immunity.

[14]  R. Yantiss,et al.  Diagnostic difficulties in inflammatory bowel disease pathology , 2006, Histopathology.

[15]  M. Castagna,et al.  STUDIO IMMUNOISTOCHIMICO DELLA GLIA ENTERICA NELLE MALATTIE INFIAMMATORIE CRONICHE INTESTINALI , 1996 .

[16]  H. Szechtman,et al.  Antidepressants attenuate increased susceptibility to colitis in a murine model of depression. , 2006, Gastroenterology.

[17]  E. Loftus Clinical epidemiology of inflammatory bowel disease: Incidence, prevalence, and environmental influences. , 2004, Gastroenterology.

[18]  M. Macey,et al.  The effect of acute psychologic stress on systemic and rectal mucosal measures of inflammation in ulcerative colitis. , 2006, Gastroenterology.

[19]  J. Olsen,et al.  Psychological Stress and Inflammatory Bowel Disease: A Follow-up Study in Parents Who Lost a Child in Denmark , 2004, American Journal of Gastroenterology.

[20]  R. Stenling,et al.  Colonic endocrine cells in inflammatory bowel disease , 1997, Journal of internal medicine.

[21]  A. Pfeufer,et al.  Differential modulation of human immunoglobulin isotype production by the neuropeptides substance P, NKA and NKB 1 Dedicated to the 60th birthday of Professor Eckart Köttgen. 1 , 1999, Journal of Neuroimmunology.

[22]  Christopher G Mathew,et al.  Genetics of inflammatory bowel disease: progress and prospects. , 2004, Human molecular genetics.

[23]  J. Galmiche,et al.  Enteric glia inhibit intestinal epithelial cell proliferation partly through a TGF-beta1-dependent pathway. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[24]  B. Cravatt,et al.  The endogenous cannabinoid system protects against colonic inflammation. , 2004, The Journal of clinical investigation.

[25]  J. Milbrandt,et al.  Ninjurin, a Novel Adhesion Molecule, Is Induced by Nerve Injury and Promotes Axonal Growth , 1996, Neuron.

[26]  M. Sjöblom,et al.  Epithelial cells and their neighbors. II. New perspectives on efferent signaling between brain, neuroendocrine cells, and gut epithelial cells. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[27]  G. Adler,et al.  Proinflammatory cytokines increase glial fibrillary acidic protein expression in enteric glia , 2004, Gut.

[28]  F. Shanahan,et al.  Manipulation of the bacterial flora in inflammatory bowel disease. , 2003, Best practice & research. Clinical gastroenterology.

[29]  Dockerty Mb,et al.  The myenteric plexus in regional enteritis: a study of the number of ganglion cells in the ileum in 24 cases. , 1955 .

[30]  D. Binion,et al.  Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation. , 2003, Gastroenterology.

[31]  H. Ahlman,et al.  Influence of Topical Rectal Application of Drugs on Dextran Sulfate-Induced Colitis in Rats , 1997, Digestive Diseases and Sciences.

[32]  S. Smid,et al.  Impaired capsaicin and neurokinin‐evoked colonic motility in inflammatory bowel disease , 2005, Journal of gastroenterology and hepatology.

[33]  K. Sharkey,et al.  Neuroimmune and epithelial interactions in intestinal inflammation. , 2002, Current opinion in pharmacology.

[34]  M. Chamaillard,et al.  Advances and perspectives in the genetics of inflammatory bowel diseases. , 2006, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[35]  P. Rutgeerts,et al.  Major histocompatibility class II expression on the small intestinal nervous system in Crohn's disease. , 1992, Gastroenterology.

[36]  T. Seufferlein,et al.  Glial-derived neurotrophic factor regulates apoptosis in colonic epithelial cells. , 2003, Gastroenterology.

[37]  H. Steinhart,et al.  Attachment Insecurity Moderates the Relationship Between Disease Activity and Depressive Symptoms in Ulcerative Colitis , 2005, Inflammatory bowel diseases.

[38]  J. Féher,et al.  Neuroimmune Interactions in Experimental Colitis , 2002, Neuroimmunomodulation.

[39]  A. Dvorak,et al.  Crohn's disease: transmission electron microscopic studies. III. Target tissues. Proliferation of and injury to smooth muscle and the autonomic nervous system. , 1980, Human pathology.

[40]  T. Muto,et al.  Distribution and quantification of somatostatin in inflammatory disease , 1992, Diseases of the colon and rectum.

[41]  B. Janic,et al.  Colonic vasoactive intestinal polypeptide (VIP) in ulcerative colitis--a radioimmunoassay and immunohistochemical study. , 1996, Hepato-gastroenterology.

[42]  M. Neunlist,et al.  Neurotransmitter coding of enteric neurones in the submucous plexus is changed in non‐inflamed rectum of patients with Crohn’s disease , 2001, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[43]  S. Bischoff,et al.  Role of mast cells and eosinophils in neuroimmune interactions regulating mucosal inflammation in inflammatory bowel disease. , 2006, Advances in experimental medicine and biology.

[44]  K. Wakai,et al.  Dietary Risk Factors for Inflammatory Bowel Disease: A Multicenter Case‐Control Study in Japan , 2005, Inflammatory bowel diseases.

[45]  S. Collins,et al.  Structural abnormalities of the nervous system in Crohn's disease and ulcerative colitis , 1998, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[46]  A. Vetuschi,et al.  Dextran Sulfate Sodium (DSS) Colitis in Rats (Clinical, Structural, and Ultrastructural Aspects) , 1999, Digestive Diseases and Sciences.

[47]  David Grundy,et al.  Signalling the state of the digestive tract , 2006, Autonomic Neuroscience.

[48]  C. Gaveriaux-Ruff,et al.  Anti-inflammatory properties of the mu opioid receptor support its use in the treatment of colon inflammation. , 2003, The Journal of clinical investigation.

[49]  Tadataka Yamada,et al.  Textbook of Gastroenterology , 1995 .

[50]  C. Bernstein,et al.  Isolation, identification, and culture of normal mouse colonic glia , 1994, Glia.

[51]  J. Maldonado,et al.  Aetiology of inflammatory bowel disease (IBD): role of intestinal microbiota and gut-associated lymphoid tissue immune response. , 2005, Clinical nutrition.

[52]  M. Zeitz,et al.  The gut as an organ of immunology , 2003, International Journal of Colorectal Disease.

[53]  Kevin J. Tracey,et al.  Nicotinic acetylcholine receptor α7 subunit is an essential regulator of inflammation , 2002, Nature.

[54]  H. Cooke Neurotransmitters in Neuronal Reflexes Regulating Intestinal Secretion , 2000, Annals of the New York Academy of Sciences.

[55]  M. Palmer,et al.  Treatment with Neurokinin-1 Receptor Antagonist Reduces Severity of Inflammatory Bowel Disease Induced by Cryptosporidium parvum , 2002, Clinical and Vaccine Immunology.

[56]  D. R. Linden,et al.  Effects of gastrointestinal inflammation on enteroendocrine cells and enteric neural reflex circuits , 2006, Autonomic Neuroscience.

[57]  G. Corrao,et al.  Risk of inflammatory bowel disease attributable to smoking, oral contraception and breastfeeding in Italy: a nationwide case-control study. Cooperative Investigators of the Italian Group for the Study of the Colon and the Rectum (GISC). , 1998, International journal of epidemiology.

[58]  D. Delbro,et al.  Adrenoceptor-mediated modulation of evans blue dye permeation of rat small intestine , 1995, Digestive diseases and sciences.

[59]  J. Galmiche,et al.  Changes in enteric neurone phenotype and intestinal functions in a transgenic mouse model of enteric glia disruption , 2005, Gut.

[60]  R. Maunder,et al.  Supportive-Expressive Group Psychotherapy for Persons with Inflammatory Bowel Disease , 2001, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[61]  S. Collins,et al.  Expression of cytokines in the longitudinal muscle myenteric plexus of the inflamed intestine of rat. , 1994, Gastroenterology.

[62]  A. Leiter,et al.  The “Normal” Endocrine Cell of the Gut: Changing Concepts and New Evidences , 2004, Annals of the New York Academy of Sciences.

[63]  A. Keshavarzian,et al.  Heightened Responses to Stressors in Patients with Inflammatory Bowel Disease , 2005, The American Journal of Gastroenterology.

[64]  T. Halstensen,et al.  The B-cell system in inflammatory bowel disease. , 2006, Advances in experimental medicine and biology.

[65]  J. Lopez-Garcia,et al.  Responses of rat spinal neurons to distension of inflamed colon: role of tachykinin NK2 receptors , 2001, Neuropharmacology.

[66]  J. Holst,et al.  Tissue levels and post-prandial secretion of the intestinal growth factor, glucagon-like peptide-2, in controls and inflammatory bowel disease: comparison with peptide YY , 2005, European journal of gastroenterology & hepatology.

[67]  S. Rose-John,et al.  The IL-6/sIL-6R fusion protein hyper-IL-6 promotes neurite outgrowth and neuron survival in cultured enteric neurons. , 1999, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[68]  K. Barrett,et al.  Chloride secretion by the intestinal epithelium: molecular basis and regulatory aspects. , 2000, Annual review of physiology.

[69]  A. Hart,et al.  Mechanisms of initiation and perpetuation of gut inflammation by stress , 2002, Alimentary pharmacology & therapeutics.

[70]  T. Bush Enteric glial cells. An upstream target for induction of necrotizing enterocolitis and Crohn's disease? , 2002, BioEssays : news and reviews in molecular, cellular and developmental biology.

[71]  H. Blaszyk,et al.  Indiscriminate loss of myenteric neurones in the TNBS‐inflamed guinea‐pig distal colon , 2005, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[72]  F. Shanahan,et al.  The role of substance P in inflammatory disease , 2004, Journal of cellular physiology.

[73]  N. Saadé,et al.  Inhibitory effect of experimental colitis on fluid absorption in rat jejunum: role of the enteric nervous system, VIP, and nitric oxide. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[74]  D. Grundy Neuroanatomy of visceral nociception: vagal and splanchnic afferent , 2002, Gut.

[75]  M. Breschi,et al.  Altered prejunctional modulation of intestinal cholinergic and noradrenergic pathways by α2‐adrenoceptors in the presence of experimental colitis , 2003, British journal of pharmacology.

[76]  K. Jacobson,et al.  Noradrenergic and cholinergic neural pathways mediate stress-induced reactivation of colitis in the rat , 2006, Autonomic Neuroscience.

[77]  C. Bernstein,et al.  On Studying the Connection Between Stress and IBD , 2006, The American Journal of Gastroenterology.

[78]  M. Jönsson,et al.  Substance P and the neurokinin-1 receptor in relation to eosinophilia in ulcerative colitis , 2005, Peptides.

[79]  F. Ponti,et al.  Enteric neuroplasticity evoked by inflammation , 2006, Autonomic Neuroscience.

[80]  K. Jacobson,et al.  Cholinergic pathways modulate experimental dinitrobenzene sulfonic acid colitis in rats , 2003, Autonomic Neuroscience.

[81]  J. Overmier,et al.  An acute stressor enhances sensitivity to a chemical irritant and increases51CrEDTA permeability of the colon in adult rats , 2005, Integrative physiological and behavioral science : the official journal of the Pavlovian Society.

[82]  J. Mawdsley,et al.  RECENT ADVANCES IN BASIC SCIENCE PSYCHOLOGICAL STRESS IN IBD: NEW INSIGHTS INTO PATHOGENIC AND THERAPEUTIC IMPLICATIONS , 2005 .

[83]  Vikram Bhatia,et al.  Stress and the gastrointestinal tract , 2005, Journal of gastroenterology and hepatology.

[84]  M. Salaspuro,et al.  Rectal mucosal adrenergic innervation and enterochromaffin cells in ulcerative colitis and irritable colon. , 1977, Scandinavian journal of gastroenterology.

[85]  G. Bubenik,et al.  Localization, Physiological Significance and Possible Clinical Implication of Gastrointestinal Melatonin , 2001, Neurosignals.

[86]  T. Nguyen,et al.  The Enteric Nervous System and Its Extrinsic Connections , 2009 .

[87]  Kernohan Jw,et al.  The myenteric plexus in chronic ulcerative colitis. , 1953 .

[88]  M. Sans,et al.  Inflammatory bowel disease: the role of environmental factors. , 2004, Autoimmunity reviews.

[89]  M. Crowell,et al.  Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. , 2004, Gastroenterology.

[90]  J. Furness Types of neurons in the enteric nervous system. , 2000, Journal of the autonomic nervous system.

[91]  K. Sharkey,et al.  Interleukin-1beta activates specific populations of enteric neurons and enteric glia in the guinea pig ileum and colon. , 2003, American journal of physiology. Gastrointestinal and liver physiology.

[92]  H. Lassmann,et al.  Enterocolitis induced by autoimmune targeting of enteric glial cells: A possible mechanism in Crohn's disease? , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[93]  M. Gulubova,et al.  Mast cells and inflammatory mediators in chronic ulcerative colitis. , 2002, Acta histochemica.

[94]  D. Haller,et al.  Intestinal epithelial cell signalling and host‐derived negative regulators under chronic inflammation: to be or not to be activated determines the balance towards commensal bacteria , 2006, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[95]  B. Yeğen,et al.  Colitis‐induced oxidative damage of the colon and skeletal muscle is ameliorated by regular exercise in rats: the anxiolytic role of exercise , 2006, Experimental physiology.

[96]  M. Fujimoto,et al.  Vasoactive intestinal peptide specifically induces human IgA1 and IgA2 production , 1994, European journal of immunology.

[97]  M. Fujimura,et al.  Changes in number of serotonin-containing cells and serotonin levels in the intestinal mucosa of rats with colitis induced by dextran sodium sulfate , 1999, Histochemistry and Cell Biology.

[98]  U. Böcker,et al.  Inflammatory Bowel Disease and Smoking: A Review of Epidemiology, Pathophysiology, and Therapeutic Implications , 2004, Inflammatory bowel diseases.

[99]  H. Cooke Neuroimmune signaling in regulation of intestinal ion transport. , 1994, The American journal of physiology.

[100]  L. Mucke,et al.  Fulminant Jejuno-Ileitis following Ablation of Enteric Glia in Adult Transgenic Mice , 1998, Cell.

[101]  S. Collins,et al.  The role of CD4+ lymphocytes in the susceptibility of mice to stress-induced reactivation of experimental colitis , 1999, Nature Medicine.

[102]  M. Hansen The enteric nervous system I: organisation and classification. , 2003, Pharmacology & toxicology.

[103]  J. Söderholm,et al.  Increased antigen and bacterial uptake in follicle associated epithelium induced by chronic psychological stress in rats , 2004, Gut.

[104]  A. Malliani,et al.  Sympathetic overactivity in active ulcerative colitis: effects of clonidine. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[105]  Hämäläinen M,et al.  Glial regulation of neuronal plasticity in the gut: implications for clinicians , 2006, Gut.

[106]  K. Kip,et al.  Crohn's Disease: A Two-Year Prospective Study of the Association Between Psychological Distress and Disease Activity , 2004, Digestive Diseases and Sciences.

[107]  C. Mittermaier,et al.  Impact of Depressive Mood on Relapse in Patients With Inflammatory Bowel Disease: A Prospective 18-Month Follow-Up Study , 2004, Psychosomatic medicine.

[108]  F. Shanahan,et al.  Neurokinin-1 receptor expression in inflammatory bowel disease: molecular quantitation and localisation , 2000, Gut.

[109]  E. Hahn,et al.  Effect of substance P on histamine secretion from gut mucosa in inflammatory bowel disease. , 1999, Scandinavian journal of gastroenterology.

[110]  T. Savidge,et al.  Role of enteric glial cells in inflammatory bowel disease , 2003, Glia.

[111]  Xing,et al.  Altered myoelectrical activity in noninflamed ileum of rats with colitis induced by trinitrobenzene sulphonic acid , 1999, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[112]  S. Hanauer,et al.  Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities , 2006, Inflammatory bowel diseases.

[113]  W. Falk,et al.  Chronic intermittent psychosocial stress (social defeat/overcrowding) in mice increases the severity of an acute DSS-induced colitis and impairs regeneration. , 2006, Endocrinology.

[114]  S. Lam,et al.  Reduction of colonic mucus by repeated short-term stress enhances experimental colitis in rats , 2001, Journal of Physiology-Paris.

[115]  M. Saruta,et al.  Urocortin 1 in colonic mucosa in patients with ulcerative colitis. , 2004, The Journal of clinical endocrinology and metabolism.

[116]  Philip Jacobs,et al.  Work losses related to inflammatory bowel disease in the United States: Results from the National Health Interview Survey , 2003, American Journal of Gastroenterology.

[117]  R. Stead Nerve Remodelling during Intestinal Inflammation a , 1992, Annals of the New York Academy of Sciences.

[118]  G. Greenberg,et al.  Autonomic response to standardized stress predicts subsequent disease activity in ulcerative colitis , 2006, European journal of gastroenterology & hepatology.

[119]  I. Hall,et al.  Eosinophil-mediated cholinergic nerve remodeling. , 2006, American journal of respiratory cell and molecular biology.

[120]  H. Raybould,et al.  Sensory mechanisms: transmitters, modulators and reflexes , 2004, Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society.

[121]  M. Blennerhassett,et al.  Damage to the enteric nervous system in experimental colitis. , 1999, The American journal of pathology.