Capsaicin attenuates hindbrain neuron responses to circulating cholecystokinin.

Abstract

Capsaicin is a neurotoxin that destroys small sensory neurons with unmyelinated axons, including a subpopulation of vagal sensory neurons. Capsaicin treatment attenuates suppression of food intake induced by systemic administration of cholecystokinin (CCK) but not by gastric distension. However, both gastric distension and intravascular CCK alter the discharge of dorsal hindbrain neurons by a vagal mechanism. Therefore, it is plausible that some hindbrain neurons receive convergent input from capsaicin-sensitive vagal neurons that are responsive to CCK and also from capsaicin-insensitive neurons that are responsive to gastric distension. To investigate this possibility we made extracellular recordings from gastric distension-responsive hindbrain neurons during intra-arterial cholecystokinin octapeptide (CCK-8) administration in anesthetized intact and capsaicin-pretreated rats. We found that capsaicin-pretreated rats exhibit attenuated neuronal discharge responses to CCK-8 but not to gastric distension. These results are consistent with the existence of convergent CCK-sensitive and gastric distension-sensitive afferent inputs to hindbrain neurons and suggest that various gastrointestinal sensory modalities may be communicated to the brain by populations of neurons that can be distinguished by their sensitivity to neurotoxins.