P2X purinoceptor-induced sensitization of ferret vagal mechanoreceptors in oesophageal inflammation

Using an in vitro single unit recording technique we studied the changes in mechanical and chemical sensitivity of vagal afferent fibres in acute oesophagitis, with particular attention to inflammatory products such as purines. Histologically verified oesophagitis was induced bq oesophageal perfusion of 1 mg ml(-1) pepsin in 150 mM HCl in anaesthetized ferrets for 30 min on two consecutive days. Controls were infused with 154 mM NaCl. The number of action potentials evoked in oesophageal mucosal afferents by mucosal stroking with calibrated von Frey hairs (10-1000mg) was stimulus dependent. In oesophagitis responsiveness was reduced across the range of stimuli compared with controls. Topical application of the P2X purinoceptor agonist alpha beta-methylene ATP had no direct excitatory effect on afferents. In oesophagitis, but not in controls, there was a significant increase in responses to stroking with von Frey hairs during superfusion with alpha beta-methylene ATP (1 mu M). Mucosal afferents responded directly to one or more chemical stimuli: 26 % (5/19 afferents) responded in controls, and 47 % (7/15 afferents) in oesophagitis. There were no differences in responsiveness to bradykinin (1 mu M), prostglandin E-2 (100 mu M), 5-hydroxytryptamine (100 mu M), capsaicin (1 mM) or hydrochloric acid (150 mM) between control and oesophagitis groups. We conclude that a sensitizing effect of a P2X purinoceptor agonist on mechanosensory function is induced in oesophagitis. This effect is offset by a decrease in basal mechanosensitivity.