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Loss of visceral pain following colorectal distension in an endothelin‐3 deficient mouse model of Hirschsprung's disease
Author(s) -
Zagorodnyuk Vladimir P.,
Kyloh Melinda,
Nicholas Sarah,
Peiris Heshan,
Brookes Simon J.,
Chen Bao Nan,
Spencer Nick J.
Publication year - 2011
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2010.202820
Subject(s) - nociception , distension , endothelin receptor , visceral pain , medicine , hirschsprung's disease , rectum , noxious stimulus , receptor , enteric nervous system , afferent , neuroscience , endocrinology , biology , disease
Non‐technical summary The endothelin‐3 (ET‐3) gene is essential for the development of the enteric nervous system in the gastrointestinal tract of mammals, including humans and mice. Loss of the ET‐3 gene leads to the formation of an aganglionic colorectum and impaired bowel function. Endogenous endothelin peptides and their receptors also play a major role in nociception in a variety of organs and species, including humans. However, whether nociception is altered in the aganglionic region of the colorectum is unknown. We show that in ET‐3 deficient mice, there is a loss of nociception from the aganglionic rectum, but not other visceral organs. This loss of nociception is due to a reduction in spinal afferent innervation and a selective deficiency in specific classes of rectal afferent nerve fibres, which are necessary for detection of noxious stimuli from this region.