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Acid sensitivity of the spinal dorsal root ganglia C‐fiber nociceptors innervating the guinea pig esophagus
Author(s) -
Ru F.,
Banovcin P.,
Kollarik M.
Publication year - 2015
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/nmo.12561
Subject(s) - trpv1 , esophagus , heartburn , nociceptor , receptor , chemistry , acid sensing ion channel , reflux , nociception , medicine , transient receptor potential channel , ion channel , biochemistry , disease
Background Gastroesophageal reflux can cause high acidity in the esophagus and trigger heartburn and pain. However, because of the esophageal mucosal barrier, the acidity at the nerve terminals of pain‐mediating C‐fibers in esophageal mucosa is predicted to be substantially lower. We hypothesized that the esophageal dorsal root ganglia ( DRG ) C‐fibers are activated by mild acid (compared to acidic reflux), and express receptors and ion channels highly sensitive to acid. Methods Extracellular single unit recordings of activity originating in esophageal DRG C‐fiber nerve terminals were performed in the innervated esophagus preparation ex vivo . Acid was delivered in a manner that bypassed the esophageal mucosal barrier. The expression of mRNA for selected receptors in esophagus‐specific DRG neurons was evaluated using single cell RT ‐ PCR . Key Results Mild acid ( pH = 6.5–5.5) activated esophageal DRG C‐fibers in a pH ‐dependent manner. The response to mild acid at pH = 6 was not affected by the TRPV 1 selective antagonist iodo‐resiniferatoxin. The majority (70–95%) of esophageal DRG C‐fiber neurons ( TRPV 1‐positive) expressed mRNA for acid sensing ion channels ( ASIC 1a, ASIC 1b, ASIC 2b, and/or ASIC 3), two‐pore‐domain (K2P) potassium channel TASK 1, and the proton‐sensing G‐protein coupled receptor OGR 1. Other evaluated targets ( PKD 2L1, TRPV 4, TASK 3, TALK 1, G2A, GPR 4, and TDAG 8) were expressed rarely. Conclusions & Inferences Guinea pig esophageal DRG C‐fibers are activated by mild acid via a TRPV 1‐independent mechanism, and express mRNA for several receptors and ion channels highly sensitive to acid. The high acid sensitivity of esophageal C‐fibers may contribute to heartburn and pain in conditions of reduced mucosal barrier function.