The broad objective of this proposal is to contribute to our understanding of how we perceive our environment. Specifically, I will be examining the systems that facilitate our perception of temperature and pan. Recently, numerous members of the TRP-family of non-specific cation channels (TRPc) have been shown to be activated in response to different ranges of temperature. TRPV1, the first thermo sensitive TRPc identified, is activated by noxious heat and has a demonstrated role in inflammation induced thermal hyperalgesia. The molecular mechanisms by which TRPcs are activated by temperature are currently unknown. ANKTM1, a putative polymodal nociceptor was recently identified as a TRP channel that responds to noxious levels of cold, the noxious compound cinnamaldehyde, the inflammatory peptide brandykinin when co-expressed with the brandykinin receptor and is expressed in a subset of nociceptive sensory neurons. The goals of this proposal are to identify specific residues/domains within ANKTM1 that confer the ability to sense noxious cold and/or cinnamaldehyde. The findings from these studies will provide a basic understanding of the mechanisms of ANKTM1 activation and may provide general insight into how temperature gates TRP channel activation. This research may also contribute to the development of therapeutic drugs to manage pain based on the identification of potential targets on the nociceptor, ANKTM1