GABA(B) receptors inhibit mechanosensitivity of primary afferent endings

The modulatory effects of baclofen on the sensitivity of peripheral afferen t endings to mechanical stimulation were investigated using an in vitro fer ret gastroesophageal vagal afferent preparation. Changes in sensitivity of three types of gastroesophageal vagal afferent endings previously categoriz ed as mucosal, tension, and tension-mucosal (TM) receptors according to the ir mechanoreceptive field characteristics were investigated. Baclofen (30-2 00 mu M) dose dependently reduced responses of mucosal afferents to mucosal stroking with calibrated von Frey hairs (10-1000 mg). This was reversed by the GABA(B) receptor antagonist SCH50911 (1 mu M). TM afferent responses t o mucosal stroking (10-1000 mg) were unaffected by baclofen (30-200 mu M). However, baclofen (30-200 mu M) significantly inhibited the response of 11 of 18 TM afferents to circumferential tension. This was reversed by SCH5091 1 (1 mM). Baclofen (100 and 200 mu M) significantly inhibited the response of all tension receptor afferents to circumferential tension in the lower r ange (1-3 gm) but not in the higher range (4-7 gm). This inhibition was rev ersed by SCH50911 (1 mu M; n = 3). This study provides the first direct evi dence for the inhibitory modulation of peripheral mechanosensory endings by the G-protein-coupled GABA(B) receptor. Inhibition was dose-dependent, pha rmacologically reversible, and selective to certain aspects of mechanosensi tivity. These findings have important relevance to strategies for selective reduction of sensory input to the CNS at a peripheral site.