GABAB Receptors Inhibit Mechanosensitivity of Primary Afferent Endings

Abstract

<jats:p>The modulatory effects of baclofen on the sensitivity of peripheral afferent endings to mechanical stimulation were investigated using an<jats:italic>in vitro</jats:italic>ferret gastroesophageal vagal afferent preparation. Changes in sensitivity of three types of gastroesophageal vagal afferent endings previously categorized as mucosal, tension, and tension–mucosal (TM) receptors according to their mechanoreceptive field characteristics were investigated. Baclofen (30–200 μ<jats:sc>m</jats:sc>) dose dependently reduced responses of mucosal afferents to mucosal stroking with calibrated von Frey hairs (10–1000 mg). This was reversed by the GABA<jats:sub>B</jats:sub>receptor antagonist SCH50911 (1 μ<jats:sc>m</jats:sc>). TM afferent responses to mucosal stroking (10–1000 mg) were unaffected by baclofen (30–200 μ<jats:sc>m</jats:sc>). However, baclofen (30–200 μ<jats:sc>m</jats:sc>) significantly inhibited the response of 11 of 18 TM afferents to circumferential tension. This was reversed by SCH50911 (1 μ<jats:sc>m</jats:sc>). Baclofen (100 and 200 μ<jats:sc>m</jats:sc>) significantly inhibited the response of all tension receptor afferents to circumferential tension in the lower range (1–3 gm) but not in the higher range (4–7 gm). This inhibition was reversed by SCH50911 (1 μ<jats:sc>m</jats:sc>;<jats:italic>n</jats:italic>= 3). This study provides the first direct evidence for the inhibitory modulation of peripheral mechanosensory endings by the G-protein-coupled GABA<jats:sub>B</jats:sub>receptor. Inhibition was dose-dependent, pharmacologically reversible, and selective to certain aspects of mechanosensitivity. These findings have important relevance to strategies for selective reduction of sensory input to the CNS at a peripheral site.</jats:p>