Acid sensitivity of the spinal dorsal root ganglia @entity7183 nociceptors innervating the XXXX esophagus.

@entity47112 @entity840 @entity7183 @entity158 @entity972 @entity54049 @entity31592
BACKGROUND: Gastroesophageal reflux can cause high acidity in the esophagus and trigger heartburn and @entity158 . However, because of the esophageal mucosal barrier, the acidity at the nerve terminals of @entity158 -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 @entity7183 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 @entity31592 selective antagonist @entity54049 . The majority (70-95%) of esophageal DRG @entity7183 neurons ( @entity31592 -positive) expressed mRNA for acid sensing ion channels (ASIC1a, ASIC1b, ASIC2b, and/or ASIC3), two-pore-domain (K2P) @entity972 channel TASK1, and the proton-sensing G-protein coupled receptor OGR1. Other evaluated targets (PKD2L1, TRPV4, TASK3, TALK1, @entity47112 , GPR4, and TDAG8) were expressed rarely. CONCLUSIONS _ INFERENCES: @entity840 esophageal DRG C-fibers are activated by mild acid via a @entity31592 -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 @entity158 in conditions of reduced mucosal barrier function.
