Central mechanisms of lower esophageal sphincter control.

Lower esophageal sphincter (LES) tone is decreased during swallowing, during transient LES relaxations (TLESRs), and before emesis, and this decrease is due primarily to increasing inhibitory vagal output to the LES. Reflex-evoked relaxation of the LES is mediated by long-loop vagovagal reflexes that are coordinated by the dorsal vagal complex in the hindbrain medulla. A sequence of events occurs. Central control of TLESRs has not been studied directly; the information on how drugs may work centrally to reduce TLESRs is extrapolated from knowledge of how the brain evokes LES relaxation. Reduction of the frequency of TLESRs by a GABAB agonist, baclofen, is due to inhibition of vagal afferents, information transfer between the nucleus tractus solitarius and dorsal motor nucleus of the vagus, and vagal efferent outflow. Preliminary data show that cannabinoid receptor activation reduces information transfer between the nucleus tractus solitarius and dorsal motor nucleus of the vagus. The potential therapeutic usefulness of these types of agents that reduce TLESRs by acting centrally is promising.