An emerging topic in nutrition research is to understand the role of spices both culturally and physiologically beyond just being taste givers. Anecdotally numerous health benefits have been ascribed to naturally derived compounds from spices but the molecular mechanisms through which spices mediate their effects remain largely unknown. Transient receptor potential (TRP) ion channels expressed in sensory neurons respond to natural compounds and especially spices and herbal medicines. For example, TRPV1 responds to the plant component capsaicin (the pungent ingredient in chilli peppers), which produces the psychophysical sensation of heat or burning, TRPM8 responds to menthol (found in peppermint), which produces a cooling sensation and TRPA1 is activated by several natural plant derived products such as mustard oil that also produces a pungent sensation. At this point these TRP channels have been studied mostly in sensory neurons –yet various studies point out ectopic expression of TRP channels such as in the gut and in the brain. What is the role of the TRP channels found in the gut? and in the brain? What are the ligands for these channels? Do the ligands for brain TRP channels originate endogenously or are they delivered through food? We plan to answer these questions studying the localization, structure activity-relationship and physiological response of these TRP channels (TRPA1, TRPM8 and TRPV1) in relation to their agonists from spices in the gastrointestinal tract and their possible benefits to human health and quality of life. In addition, we will carry out the study of distribution and physiology of the selected channels in the brain since it has been demonstrated that the overall level of TRP channel mRNAs is highest in brain areas and recent studies suggested that some pungent low molecular weight constituents of spicy food could easily cross the blood-brain barrier, enter the brain and act directly in a way, which is yet to be determined.