Role of Piezo1 in Mechanical Touch and Nociception
Role of Piezo1 in Mechanical Touch and Nociception
批准号:
10350033
负责人:
Vanessa Ehlers
金额:
$6.6万
依托单位国家:
美国
项目类别:
财政年份:
2021
资助国家:
美国
项目状态:
已结题
起止时间:
2021-12-01 至 2024-11-30
中文摘要
项目总结
英文摘要
PROJECT SUMMARY
Detection of mechanical stimuli is crucial for organisms' development and survival. Discriminating between an
innocuous mechanical stimulus and noxious mechanical force is vital to avoid tissue damage and resulting pain.
Cutaneous mechanisms of mechanical stimulus detection have received considerable attention, however, the
sensory neuron-specific mechanoreceptors underlying touch and pain are not fully understood. Piezo1 and
Piezo2 ion channels are bona fide mechanotransduction cation channels expressed at various levels and tissues
that comprise the peripheral nervous system, including keratinocytes and sensory neurons. While sensory
neuron expression of Piezo2 is essential for peripheral sensation of tactile stimuli, relatively little is known about
the role of its close relative, Piezo1. Despite early work suggesting dorsal root ganglia (DRG) sensory neurons
display relatively robust Piezo2 expression and comparatively minimal Piezo1 expression, more recent evidence
suggests that Piezo1 is expressed by sensory neurons and it can be mechanically and pharmacologically
activated in these neurons. This suggests sensory neuron Piezo1 may be functionally important for detection of
tactile and mechanical pain by the somatosensory system. Furthermore, while sensory neuron Piezo2 is
implicated in mechanical allodynia, nothing is currently known about the contribution of sensory neuron Piezo1
to the mechanical allodynia or hyperalgesia characteristic of neuropathic or inflammatory pain conditions. In the
experiments outlined in the current proposal, I will use evoked behavioral assays, patch clamp electrophysiology,
and ex vivo skin-nerve recordings to determine the role Piezo1 plays in sensory neuron-mediated
mechanosensation in naïve (non-injury) and pain (injury) contexts by using transgenic mice with sensory neuron
specific deletion of Piezo1. In Aim 1, I will examine the contribution of sensory neuron-specific Piezo1 to
mechanosensation (Aim 1A), to mechanically-evoked peripheral fiber responses (Aim 1B), and to DRG
responses to mechanical stimuli (Aim 1C). Similar approaches will be used in Aim 2 to interrogate the role of
Piezo1 in mechanical hypersensitivity induced by inflammation, using complete Freund's adjuvant, and
peripheral neuropathy induced by spared tibial nerve injury. I will determine whether Piezo1 contributes to injury-
induced mechanical allodynia and hyperalgesia (Aim 2A), and mechanical stimulus-induced sensitization of
peripheral fibers (Aim 2B) and DRG sensory neurons (Aim 3C). These studies will ultimately reveal additional
roles for mechanically-gated channels in tactile stimulus transduction. Overall, the proposed aims will reveal the
contribution of sensory neuron Piezo1 to detection of mechanical stimuli in non-injury and injury conditions,
potentially revealing new avenues for treatment of mechanical pain.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Role of Piezo1 in Mechanical Touch and Nociception
-
批准号:10536601
-
项目类别:
-
资助金额:$6.95万
-
财政年份:2021
-
负责人:Vanessa Ehlers
-
依托单位:
国内基金
海外基金
登录
查看更多内容
针刺靶向Piezo1通道调控脑缺血再灌注损伤大鼠线粒体依赖性凋亡的机制
-
批准号:2026JJ81955
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:王井泉
-
依托单位:
Piezo1感知肿瘤硬度介导视黄醇代谢重编程调控肝癌免疫治疗疗效的机制研究
-
批准号:2026JJ60089
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:谭黉沛
-
依托单位:
机械敏感离子通道Piezo1通过FBP1驱动巨噬细胞糖酵解破坏心脏免疫稳态加重脓毒性心肌病的机制研究
-
批准号:JCZRLH202600103
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
黄芪多糖调控HDAC6 O-GlcNAcylation影响Piezo1介导的铁死亡参与激素性股骨头坏死的机制研究
-
批准号:2026JJ81341
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:张申尧
-
依托单位:
化痰通络汤调控PIEZO1/ACSL4/VEGF轴阻断线粒体机械转导增强内皮细胞铁死亡抗性促缺血性中风后血管新生的机制研究
-
批准号:2026JJ81884
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:朱新华
-
依托单位:
粘弹性水凝胶通过Piezo1调控YAP信号通路促进脑膜淋巴管生成在交通性脑积水中的作用及机制
-
批准号:2026JJ82470
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:王衡
-
依托单位:
慢性睡眠剥夺通过神经-免疫轴激活Piezo1/YAP通路加剧动脉粥样硬化的机制研究
-
批准号:
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:张文韬
-
依托单位:
机械敏感离子通道蛋白Piezo1在炎症性肠病中的功能定位及机制研究
-
批准号:JCZRQNB202600014
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
基于Piezo1信号轴探讨经穴推拿“筋骨同治”法协同抑制滑膜与软骨细胞焦亡改善KOA的机制研究
-
批准号:JCZRLH202602089
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:
-
依托单位:
Piezo1驱动的人工合成TCR-T精准靶向肝癌的治疗研究
-
批准号:2026JJ60274
-
项目类别:省市级项目
-
资助金额:--
-
批准年份:2026
-
负责人:肖潺潺
-
依托单位: