Mouthfeel refers to the physical or textural sensations in the mouth caused by foods and beverages that are essential to the acceptability of many edible products. The sensory subqualities contributing to mouthfeel are often chemogenic in nature and include heat, burning, cooling, tingling, and numbing. These “chemesthetic” sensations are a result of the chemical activation of receptors that are associated with nerve fibers mediating pain and mechanotransduction. Each of these chemesthetic sensations in the oral cavity are transduced in the nervous system by a combination of different molecular channels/receptors expressed on trigeminal nerve fibers that innervate the mouth and tongue. The molecular profile of these channels and receptors involved in mouthfeel include many transient receptor potential channels, proton-sensitive ion channels, and potassium channels to name a few. During the last several years, studies using molecular and physiological approaches have significantly expanded and enhanced our understanding of the neurobiological basis for these chemesthetic sensations. The purpose of the current review is to integrate older and newer studies to present a comprehensive picture of the channels and receptors involved in mouthfeel. We highlight that there still continue to be important gaps in our overall knowledge on flavor integration and perception involving chemesthetic sensations, and these gaps will continue to drive future research direction and future investigation.

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