title: Identification of medium/high-threshold extrinsic mechanosensitive afferent nerves to the gastrointestinal tract.
abstract: OBJECTIVE
  Large distentions reliably evoke sensation from the noninflamed, nonischemic bowel, but the specialized afferent axonal structures responsible have not been morphologically identified. We investigated whether their transduction sites are located on major blood vessels close to and within the gut wall.
  
  
  METHODS
  In vitro extracellular recordings were made from mesenteric nerve trunks in guinea pig ileum, combined with rapid axonal dye filling and immunohistochemical analysis of nerve trunks.
  
  
  RESULTS
  Recordings revealed sensory fibers with focal mechanosensitive sites in the mesenteries that could be activated by von Frey hairs and by stretch. Dye filling revealed varicose branching sensory axons on mesenteric blood vessels but no other anatomically specialized structures in mesenteric membranes or the serosa. Large-amplitude stretch and von Frey hairs also activated sensory endings within the gut wall itself but only if the submucosa was present; mechanotransduction sites in the serosa or outer muscle layers were sparse. Mechanosensitive sites in submucosa were exclusively associated with submucosal blood vessels. Submucosal endings had significantly higher thresholds to stretch than specialized low-threshold mechanoreceptors characterized previously in the rectum (P < .05) and were therefore classified as medium/high-threshold mechanoreceptors. Capsaicin (0.3-1 micromol/L) activated most mechanosensitive mesenteric (68%) and submucosal (85%) afferent endings. Similar intramural mechanosensitive afferent endings on blood vessels also exist in the colon and bladder.
  
  
  CONCLUSIONS
  Varicose branching axons of sensory neurons on intramural blood vessels, previously shown to mediate sensory vasodilation, are transduction sites for medium/high-threshold, stretch-sensitive mechanoreceptors, encoding large distentions in hollow viscera.
authors.affiliation: Department of Human Physiology, Flinders University, Bedford Park, South Australia, Australia.
authors.forename: Xingyun
authors.initials: X
authors.lastname: Song
authors.forename: Bao Nan
authors.initials: BN
authors.lastname: Chen
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Zagorodnyuk
authors.forename: Penny A
authors.initials: PA
authors.lastname: Lynn
authors.forename: L Ashley
authors.initials: LA
authors.lastname: Blackshaw
authors.forename: David
authors.initials: D
authors.lastname: Grundy
authors.forename: Alan M
authors.initials: AM
authors.lastname: Brunsden
authors.forename: Marcello
authors.initials: M
authors.lastname: Costa
authors.forename: Simon J H
authors.initials: SJ
authors.lastname: Brookes
mesh_terms: D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003106:Colon / Q000098:blood supply / Q000294:innervation; D017615:Enteric Nervous System / Q000187:drug effects / Q000502:physiology*; D005071:Evoked Potentials; D006168:Guinea Pigs; D007082:Ileum / Q000098:blood supply* / Q000294:innervation*; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D008638:Mesenteric Arteries / Q000294:innervation*; D008642:Mesenteric Veins / Q000294:innervation*; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology*; D012684:Sensory Thresholds; D013314:Stress, Mechanical; D013997:Time Factors; D001743:Urinary Bladder / Q000098:blood supply / Q000294:innervation
chemical_list: D002211:Capsaicin