Sensitization of TRPV3 in keratinocytes versus sensory neurons as a mechanism of hyperalgesia

热激活离子通道TRPV3在炎症和神经病理性痛觉过敏的发展中的作用将使用角质形成细胞和/或DRG中缺乏TRPV3的组织特异性条件性基因敲除小鼠来研究。在活体行为测试、药理学和体外实验中，人们将利用天然感觉神经元的电生理学来确定角质形成细胞和/或背根神经节中TRPV3的缺失是否与炎性痛觉过敏的缺失有关，即已发表的普通TRPV3缺陷小鼠的表型。细胞和分子生物学技术，包括免疫组织化学和激光TIRF，将被用来研究TRPV3是如何在角质形成细胞和/或DRG中增敏的。预期的结果将为了解在基础、炎症和神经病变条件下伤害性热刺激是如何在初级感觉神经元中转导的。

The contribution of the heat-activated ion channels TRPV3 to the development ofinflammatory and neuropathic hyperalgesia will be investigated using tissue specificconditional knockout mice that lack TRPV3 in keratinocytes and/or DRGs. In vivobehavioural testing and pharmacology and in vitro electrophysiology on nativesensory neurons will be used to find out whether the lack of TRPV3 in eitherkeratinocytes and/or DRGs is responsible for the lack of inflammatory hyperalgesia,i.e. the published phenotype of general TRPV3 deficient mice. Techniques of cellularand molecular biology including also immunohistochemistry and laser TIRF will beused to investigate how sensitization of TRPV3 in either keratinocytes and /or DRGs.The expected findings will provide insight how noxious thermal stimuli are transducedin primary sensory neurons under basal, inflammatory and neuropathic conditions.