Pain Coding by TRP Channels in Polymodal Nociceptors

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DESCRIPTION (provided by applicant): Evidence suggests that temperature and pain sensation in the somatosensory system may be mediated by Transient Receptor Potential (TRP) channels, but this conclusion remains uncertain. To test this hypothesis, it will be necessary to characterize TRP channel function within a defined cell type of intact neurons within their neural circuit. These experiments will determine which TRP channels, if any, mediate pain responses in polymodal nociceptors (PNs) in an ex vivo mouse trigeminal ganglion preparation. PNs, which respond to a range of painful stimuli, will be identified by their calcium responses to heat, cold, and pinch, and their neural coding of painful stimuli and TRP channel expression will be characterized. To confirm the role of the expressed TRP channels in pain responses, wild type PN responses to heat, cold and pinch will be compared to those of knockout mice lacking specific heat and cold sensitive TRP channels. By determining which TRP channels, if any, mediate pain responses in PNs, these experiments will be a crucial step towards understanding sensory transduction of temperature and pain in the somatosensory system and towards identifying potential molecular targets for alleviating pain.