Pain Coding by TRP Channels in Polymodal Nociceptors

描述（由申请人提供）：有证据表明，体感系统中的温度和疼痛感觉可能由瞬时受体电位（TRP）通道介导，但该结论仍不确定。为了检验这一假设，有必要在其神经回路内的完整神经元的定义的细胞类型内表征TRP通道功能。这些实验将确定哪些TRP通道（如果有的话）介导离体小鼠三叉神经节制备物中的多模态伤害感受器（PN）中的疼痛反应。PN，响应于一系列的疼痛刺激，将通过其钙响应热，冷，捏，和他们的疼痛刺激和TRP通道表达的神经编码的特征。为了证实表达的TRP通道在疼痛反应中的作用，将野生型PN对热、冷和捏的反应与缺乏特异性热和冷敏感性TRP通道的敲除小鼠的那些进行比较。通过确定哪些TRP通道（如果有的话）介导PN中的疼痛反应，这些实验将是理解体感系统中温度和疼痛的感觉转导以及确定缓解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.