Topical bile acid at low pH stimulates gastric mucosal blood flow (GMBF), thereby limiting injury to surface epithelial cells (SEC). Capsaicin-sensitive afferent neurons (ASN) are possible mediators of the GMBF response and, therefore, of mucosal protection. In order to investigate the effect of topical capsaicin (ASN stimulant) and topical lidocaine (ASN inhibitor) on SEC exfoliation and GMBF, vascularized wedges of canine gastric corpus were mounted in lucite chambers. Mucosae were pretreated for 15 min with saline (NSS), 160 microM capsaicin (CAP), 4% lidocaine (LIDO), or CAP and LIDO, followed by a 30-min exposure to acid test solution (ATS; pH 1.2). The same mucosae were then pretreated in an identical fashion followed by a second 30-min exposure to 5 mM taurocholate (5 TC; pH 1.2). Parameters evaluated during both ATS and 5 TC periods were the luminal accumulation of DNA (DNAE, a sensitive marker of SEC exfoliation) and GMBF measured using radiolabeled microspheres. It was found that, relative to NSS pretreatment, CAP pretreatment increased GMBF and decreased DNAE during exposure to both ATS and 5 TC. LIDO blocked the CAP effect on GMBF but not on DNAE. Thus, ASN stimulation by CAP enhances GMBF and is protective. ANS inhibition blocks CAP's GMBF increase but not its protective capabilities. Therefore, augmentation of GMBF is not the only mechanism by which ASNs blunt SEC exfoliation.