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1 Pharmacology, University of Iowa, Iowa city, Iowa, USA
2 Internal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
* To whom correspondence should be addressed. E-mail: khoa-dang{at}uiowa.edu.
Tissue inflammation contributes to the development of hyperalgesia, which is at least in part due to altered properties of primary afferent neurons. We hypothesized that gastric ulcers enhance the excitability of gastric sensory neurons and increase their response to purinergic agonists. The rat stomach was surgically exposed and a retrograde tracer (DiI) was injected into the wall of the distal stomach. Kissing ulcers (KU) were produced by a single injection of acetic acid (0.1ml for 45 s; 60%) into the clamped gastric lumen. Saline injection served as control. Gastric nodose ganglion (NG) or dorsal root ganglion (DRG) cells were harvested 7 days later and acutely dissociated for whole-cell recordings. Based on whole cell capacitance, gastric DRG neurons exhibited larger cell size than did NG neurons. Significantly more control gastric DRG neurons compared with NG counterparts had tetrodotoxin-resistant action potentials. Almost all control NG neurons (90 %) compared with significantly less DRG neurons (
38 %) responded to ATP or 
,
-metATP.While none of the control cells exhibited spontaneous activity, about 20 % of the neurons from KU animals generated spontaneous action potentials. KU enhanced excitability as shown by a decrease in threshold for action potential generation, which was in part due to an increased input resistance. This was associated with an increase in the fraction of neurons with tetrodotoxin-resistant action potentials and cells responding to capsaicin and purinergic agonists. KU doubled the current density evoked by the P2X receptor agonist ,-metATP and slowed decay of the slowly desensitizing component of the current without affecting the concentration-dependence of the response. These data demonstrate that KU sensitizes vagal and spinal gastric afferents by affecting both voltage- and ligand-gated channels, thereby potentially contributing to the development of dyspeptic symptoms.
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