Sensory nervous system plays key role in inflammatory bowel disease

FAU researchers discover new treatment alternatives

Chronic inflammatory bowel disease (IBD) is not only painful and extremely onerous for sufferers, but also poses a major risk to health – the final outcome in many cases being a cancer diagnosis. Research scientists from Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Erlangen University Hospital have now discovered a new neuro-immune pathway which plays a crucial role in the development of colitis. Dr. Matthias Engel and Prof. Dr. Peter Reeh from the Institute of Physiology and Pathophysiology, and Prof. Dr. Markus Neurath from Medical Clinic 1, have been able to prove that the TRPA1 receptor channel plays a pivotal role in experimentally induced inflammatory bowel disease. The scientists’ research findings have been published in the renowned journal “Gastroenterology” (www.ncbi.nlm.nih.gov/pubmed/21763243)

The receptor channel in question is found in sensory nerve fibres in the intestinal tissue and is responsible for the processing of chemically, and indirectly, of mechanically induced pain stimuli. Upon activation, it releases inflammation-inducing neuropeptides such as “substance P”. “Genetically modified mice that do not have the TRPA1 receptor are immune to the experimentally induced colitis”, explains project leader Dr. Matthias Engel. “Blocking the receptor channel induces the same effect.” The drug administered by the medical scientists to achieve this is yet to be approved. However, blocking the receptor channel in this way meant the experimental introduction of intestinal inflammation ¬– usually induced via the administration of TNBS (trinitrobenzene sulphonic acid) – was no longer possible.

Initially, the scientists had discovered that TNBS directly activates the sensory nerve endings via the activation of the TRPA1 receptor channel. The next logical step was to investigate the development of various forms of inflammatory bowel disease in genetically modified mice that do not have this receptor channel. The fact that medicinally blocking TRPA1 protects against colitis and even that sick animals could be cured this way provides clinicians with reason for optimism: “The deactivation of this receptor channel does not just mean that the pain caused by inflammation can be disabled, but that the illness itself can be cured!” This promises entirely new prospects for recovery for patients with chronic inflammatory bowel disease.

Nowadays, it is not only known that chronic inflammatory bowel disease such as ulcerative colitis and Crohn’s disease are autoimmune diseases, but also that they are the result of a leakage in the barrier between the intestinal flora and intestinal mucosa. “However, the key to understanding these diseases lies in controlling the inflammatory processes”, of this the Erlangen research team is certain.

The clinicians’ research focuses, in particular, on the role of the nervous system. At the core of this research, alongside the TRPA1 receptor channel, is “substance P” – a neuropeptide which is released by sensory nerve fibres and promotes inflammation. “The TRPA1 receptor channel is essentially responsible for the release of ‘substance P’”, says physiology professor, Peter Reeh.

The TRPA1 receptor channel and “substance P” connect neurological and immunological processes in colitis. They form a decisive “neuro-immune pathway” in experimentally induced inflammatory bowel disease. The breaking of this pathway by pharmacological means does not only make it possible to treat the symptoms of chronic inflammatory bowel disease and alleviate pain, but it also means a realistic chance of recovery for the patient. “We have been successful in curing mice by deactivating the receptor channel and we hope that our findings will allow us to do the same for humans in the near future”, says Dr. Engel.

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uni | media service | research No. 53/2011 on 8.11.2011