Pain Coding by TRP Channels in Polymodal Nociceptors

描述（由申请人提供）：有证据表明，体感觉系统中的温度和痛觉可能是由瞬时受体电位（TRP）通道介导的，但这一结论仍不确定。为了验证这一假设，有必要在神经回路中完整神经元的特定细胞类型中表征TRP通道的功能。这些实验将确定在离体小鼠三叉神经节制备中，哪些TRP通道（如果有的话）介导多模伤害感受器（PNs）的疼痛反应。PNs对一系列疼痛刺激作出反应，将通过它们对热、冷和捏的钙反应来识别，它们对疼痛刺激的神经编码和TRP通道表达将被表征。为了确认表达的TRP通道在疼痛反应中的作用，我们将野生型PN对热、冷和捏的反应与缺乏特定热和冷敏感TRP通道的敲除小鼠进行比较。通过确定哪些TRP通道（如果有的话）介导PNs中的疼痛反应，这些实验将是理解体感觉系统中温度和疼痛的感觉转导以及确定减轻疼痛的潜在分子靶点的关键一步。

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.