P2X purinoceptor-induced sensitization of ferret vagal mechanoreceptors inoesophageal inflammation

Using an in vitro single unit recording technique we studied the changes in mechanical and chemical sensitivity of vagal afferent fibres in acute oeso phagitis, with particular attention to inflammatory products such as purine s. Histologically verified oesophagitis was induced bq oesophageal perfusion o f 1 mg ml(-1) pepsin in 150 mM HCl in anaesthetized ferrets for 30 min on t wo 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 de pendent. In oesophagitis responsiveness was reduced across the range of sti muli compared with controls. Topical application of the P2X purinoceptor agonist alpha beta-methylene AT P had no direct excitatory effect on afferents. In oesophagitis, but not in controls, there was a significant increase in responses to stroking with v on 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 oesoph agitis. 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 mech anosensory function is induced in oesophagitis. This effect is offset by a decrease in basal mechanosensitivity.