title: Role of sensory neurons in colitis: increasing evidence for a neuroimmune link in the gut.
abstract: Growing evidence suggests a crucial involvement of extrinsic sensory neurons in the aberrant immune response in colitis. Activation of sensory neurons is accompanied by a release of the neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), which induce neurogenic inflammation characterized by vasodilatation, plasma extravasation, and leukocyte migration. Although the role of these neuropeptides in experimental colitis and human inflammatory bowel disease (IBD) remains controversial, numerous data indicate a functional role for sensory neurons. In fact, chemical desensitization or surgical denervation of sensory nerves were shown to attenuate experimental colitis. Furthermore, pharmacological blockade of the neurokinin-1 (NK1) receptor was demonstrated to be efficient in chemically induced mouse models of colitis, and, intriguingly, also in immune-mediated models of colitis (T-cell transfer colitis). Finally, the genetic deletion or pharmacological blockade of receptor channels such as TRPV1 and TRPA1 on nociceptive sensory neurons was also demonstrated to be effective in treating experimental colitis, supposedly by inhibiting neuropeptide release. In summary, we are only beginning to understand the mechanisms of how sensory neurons modulate immune cellular actions. These findings highlight a new role of sensory neurons in chronic intestinal inflammation and suggest new avenues for therapy of IBD.
authors: Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany. engel@physiologie1.uni-erlangen.de
authors: Matthias A
authors: MA
authors: Engel
authors: Christoph
authors: C
authors: Becker
authors: Peter W
authors: PW
authors: Reeh
authors: Markus F
authors: MF
authors: Neurath
mesh_terms: D000818:Animals; D003092:Colitis / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000276:immunology*; D006801:Humans; D051379:Mice; D011984:Sensory Receptor Cells / Q000276:immunology*