Histamine 1 receptor antagonism as novel treatment for IBS

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder characterized by abdominal discomfort and pain associated with altered defecation in the absence of an organic cause. Aberrant abdominal pain perception or visceral hypersensitivity is the most disturbing and therapy resistant symptom in IBS, but the underlying pathophysiological mechanisms remain largely unknown. Mast cell activation is proposed to be involved in abnormal abdominal pain perception in IBS. Somatic pain studies indicate sensitization of nociceptors (TRPV1, TRPV4 and TRPA1) is a major mechanism by which inflammatory mediators induce increased pain perception. In the same line, we here hypothesize that mast cell mediators (histamine, serotonin, tryptase) not only directly activate visceral efferents, but also sensitize nociceptors leading to abnormal pain perception or visceral hypersensitivity. In the present project therefore, I will assess the role of mast cell mediators on sensitization of the nociceptors TRV1, TRPV4 and TRPA1 in human submucosal neurons of rectal biopsies, murine nociceptive neurons of dorsal root ganglia and murine afferent nerves. In addition, the molecular mechanisms underlying TRP sensitization will be investigated. The results of this project will be of crucial importance to improve our insight in IBS and will lead to a more efficient treatment strategy for visceral pain.

Jaar van publicatie:2018

Toegankelijkheid:Open