title: Identification of functional intramuscular rectal mechanoreceptors in aganglionic rectal smooth muscle from piebald lethal mice.
abstract: The mechanosensitive endings of low-threshold, slowly adapting pelvic afferents that innervate the rectum have been previously identified as rectal intraganglionic laminar endings (rIGLEs) that lie within myenteric ganglia. We tested whether the aganglionic rectum of piebald-lethal (s(l)/s(l)) mice lacks rIGLEs and whether this could explain impaired distension-evoked reflexes from this region. Extracellular recordings were made from fine rectal nerves in C57BL/6 wild-type and s(l)/s(l) mice, combined with anterograde labeling. In C57BL/6 mice, graded circumferential stretch applied to the rectum activated graded increases in firing of slowly adapting rectal mechanoreceptors. In s(l)/s(l) mice, graded stretch of the aganglionic rectum activated similar graded increases in rectal afferent firing. Stretch-sensitive afferents responded at low mechanical thresholds and fired more intensely at noxious levels of stretch. They could also be activated by probing their receptive fields with von Frey hairs and by muscle contraction. Anterograde labeling from recorded rectal nerves identified the mechanoreceptors of muscular afferents in the aganglionic rectal smooth muscle. A population of afferents were also recorded in both C57BL/6 and s(l)/s(l) mice that were activated by von Frey hair probing, but not stretch. In summary, the aganglionic rectum is innervated by a population of stretch-sensitive rectal afferent mechanoreceptor which develops and functions in the absence of any enteric ganglia. These results suggest that in patients with Hirschsprung's disease the inability to activate extrinsic distension reflexes from the aganglionic rectum is unlikely to be due to the absence of stretch-sensitive extrinsic mechanoreceptors.
authors.affiliation: Dept. of Human Physiology, School of Medicine, Flinders Univ., South Australia, Australia. nicholas.spencer@flinders.edu.au
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Spencer
authors.forename: Aoife
authors.initials: A
authors.lastname: Kerrin
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zagorodnyuk
authors.forename: Grant W
authors.initials: GW
authors.lastname: Hennig
authors.forename: Melodie
authors.initials: M
authors.lastname: Muto
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Brookes
authors.forename: Orla
authors.initials: O
authors.lastname: McDonnell
mesh_terms: D000200:Action Potentials; D000344:Afferent Pathways / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D017615:Enteric Nervous System / Q000473:pathology / Q000503:physiopathology*; D005804:Genes, Lethal; D006627:Hirschsprung Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008465:Mechanoreceptors / Q000473:pathology / Q000503:physiopathology*; D040542:Mechanotransduction, Cellular; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000294:innervation* / Q000503:physiopathology; D010812:Physical Stimulation; D016116:Piebaldism / Q000235:genetics*; D011312:Pressure; D012007:Rectum / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology; D012018:Reflex; D012684:Sensory Thresholds; D013127:Spinal Nerves / Q000503:physiopathology; D013997:Time Factors