title: Identifying spinal sensory pathways activated by noxious esophageal acid.
abstract: BACKGROUND
  The transient receptor potential vanilloid 1 (TRPV1) channel is critical for spinal afferent signaling of burning pain throughout the body. Such pain frequently originates from the esophagus, following acid reflux. The contribution of TRPV1 to spinal nociceptor signaling from the esophagus remains unclear. We aimed to identify the spinal afferent pathways that convey nociceptive signaling from the esophagus, specifically those sensitive to acid, and the extent to which TRPV1 contributes.
  
  
  METHODS
  Acid/pepsin (150 mM HCl/1 mg mL(-1) pepsin) or saline/pepsin was perfused into the esophageal lumen of anesthetized wild-type and TRPV1 null mice over 20 min, followed by atraumatic perfuse fixation and removal of the cervical and thoracic spinal cord and dorsal root ganglia (DRG). To identify neurons responsive to esophageal perfusate, immunolabeling for neuronal activation marker phosphorylated extracellular receptor-regulated kinase (pERK) was used. Labeling for calcitonin gene-related peptide (CGRP) and isolectin B4 (IB4) was then used to characterize responsive neurons.
  
  
  RESULTS
  Esophageal acid/pepsin perfusion significantly increased the number of pERK-immunoreactive (IR) neurons in the DRG and the cervical and thoracic spinal cord dorsal horn (DH) relative to saline/pepsin (DRG P < 0.01; cervical DH P < 0.05 and thoracic DH P < 0.005). The number of pERK-IR neurons following acid perfusion was significantly attenuated in TRPV1 -/- mice (DH P < 0.05 and DRG P < 0.05).
  
  
  CONCLUSIONS
  This study has identified populations of spinal afferent DRG neurons and DH neurons involved in signaling of noxious acid from the esophagus. There is a major contribution of TRPV1 to signaling within these pathways.
authors.affiliation: Nerve-Gut Research Laboratory, Discipline of Medicine, Faculty of Health Sciences, The University of Adelaide, Adelaide, South Australia, Australia; Department of Gastroenterology and Hepatology, Hanson Institute, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors.forename: A M
authors.initials: AM
authors.lastname: Harrington
authors.forename: S M
authors.initials: SM
authors.lastname: Brierley
authors.forename: N J
authors.initials: NJ
authors.lastname: Isaacs
authors.forename: R L
authors.initials: RL
authors.lastname: Young
authors.forename: L Ashley
authors.initials: LA
authors.lastname: Blackshaw
mesh_terms: D000344:Afferent Pathways / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D004947:Esophagus / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D005260:Female; D005744:Gastric Acid; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010146:Pain; D010434:Pepsin A / Q000633:toxicity*; D013116:Spinal Cord / Q000166:cytology; D050916:TRPV Cation Channels / Q000378:metabolism*
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D010434:Pepsin A
keywords: TRPV1; acid reflux; esophagus; pain; spinal cord