Calcium Signaling in Peripheral Sensory Nerve Endings
周围感觉神经末梢的钙信号传导
基本信息
- 批准号:10606853
- 负责人:
- 金额:$ 4.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-01-01 至 2025-10-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAfferent NeuronsAmericanAnalgesicsAttenuatedBehaviorBehavior assessmentBehavioralBrainCalciumCalcium ChannelCalcium Channel BlockersCalcium SignalingCapsaicinCentral Nervous SystemCollaborationsCommunicationComputational TechniqueDataDependenceDevelopmentEnvironmentEventFellowshipGeneticHypersensitivityImageImaging TechniquesIndividualInflammationInjuryInvestigationKnowledgeLifeMachine LearningMaintenanceMeasuresMechanicsMechanoreceptorsMediatingMethodologyMethodsModalityMusNerve EndingsNervous SystemNeuroimmuneNeuronal PlasticityNeuronsNociceptorsOutputPainPeripheralPeripheral NervesPharmacologyPlayPopulationProcessPythonsReceptor ActivationResearchResistanceResourcesRoleScienceScientistSensorySensory Nerve EndingsSensory ReceptorsSignal PathwaySignal TransductionSiteSkinSpeedSpinal CordStimulusSynaptic plasticityTherapeuticTimeTouch sensationTrainingUniversitiesViral VectorWorkbehavioral responsecareerchronic painchronic painful conditiondelivery vehicleexperienceexperimental studyimprovedin vivoin vivo calcium imagingin vivo imaginginsightintercellular communicationinterestlarge datasetsmechanotransductionmouse modelneurogeneticsneurotransmissionnoveloptogeneticspain behaviorpharmacologicprescription opioidsensory stimulusside effectskillsstatisticstherapeutic targettooltransmission processtwo-photonvoltage
项目摘要
PROJECT SUMMARY
Millions of Americans suffer from unrelenting chronic pain conditions that are resistant to existing
treatments, and those who turn to opioid medication can develop dependencies that are devastating and
life threatening. There is essential need for more effective, non-addictive analgesics with limited side
effects. Voltage-gated calcium (CaV) channels are potential targets for improved pain therapeutics. CaV
channels are critical in altering sensory neuron sensitivity and in transmitting information about noxious
stimuli. Changes in sensitivity of sensory neurons to stimuli – such as heat and touch - can result in
transient forms of hypersensitivity and, if the stimulus is prolonged or especially intense, more prolonged
hypersensitivity, which can lead to chronic pain. CaV channels in the spinal cord are important for the
induction and maintenance of hypersensitivity, but the Lipscombe lab has recently shown that peripheral
CaV2.2 channels in heat sensing neurons in skin are also critical for this process. This proposal will
expand this discovery to investigate the functional contribution of peripheral CaV channels to
hypersensitivity in Trpv1-nociceptor and Aδ low threshold mechanoreceptor (Aδ LTMR) nerve endings in
skin. In Aim 1, optogenetics and automated, real-time behavior tracking with high-speed videography will
be combined to assess behavioral responses induced by direct activation of either Trpv1-nociceptor
(heat-sensing) or Aδ LTMRs (mechano-sensing). Changes in evoked behavior will be assessed following
sensitization of either neuron population as well as the potential for selective inhibition of peripheral CaV
channels to attenuate these outputs. Aim 2 will investigate intracellular calcium dynamics in nerve
endings in skin associated with the development of hypersensitivity. Integration of optogenetics, 2-photon
in vivo calcium imaging, and pharmacology, will uncover the individual contribution of CaV2.2 and CaV3.2
channels to calcium events in Trpv1-nociceptor and Aδ LTMRs that trigger hypersensitivity. This work
will provide unique data on the role of peripheral CaV channels in the induction of hypersensitivity and
may identify novel sites of action for developing more effective pain therapeutics, thereby reducing
unwanted side effects from actions in the central nervous system. The proposed research builds on the
applicant’s experience and provides an opportunity to develop unique expertise in genetic, behavioral, 2-
photon imaging and computation techniques. Collaborating with the Fleischmann and Moore labs for 2-
photon calcium imaging gives the applicant essential experience in team science and integrating across
different levels of investigation. This fellowship will also support the applicant’s professional development
in rigorous scientific methods and effective scientific communication. The Brain Science environment at
Brown University is exceptional for training, it provides numerous avenues for support, training, and
resources to prepare the applicant for a career as an independent academic scientist.
项目摘要
数以百万计的美国人遭受无情的慢性疼痛状况,
治疗,而那些转向阿片类药物的人可能会产生毁灭性的依赖性,
危及生命有必要对更有效的,非成瘾性的镇痛剂,有限的副作用,
方面的影响.电压门控钙(CaV)通道是改善疼痛疗法的潜在靶点。Cav
通道在改变感觉神经元的敏感性和传递有害物质的信息方面至关重要。
刺激。感觉神经元对刺激(如热和触摸)的敏感性变化可能导致
短暂形式的超敏反应,如果刺激持续时间长或特别强烈,则更长
过敏,这可能导致慢性疼痛。脊髓中的CaV通道对于
诱导和维持超敏反应,但Lipscombe实验室最近表明,外周
皮肤中的热感受神经元中的CaV2.2通道对于这一过程也是至关重要的。这项建议会
扩展这一发现,以研究外周CaV通道的功能贡献,
大鼠Trpv 1-伤害性感受器和Aδ低阈值机械感受器(Aδ LTMR)神经末梢超敏反应
皮肤在目标1中,光遗传学和自动化,实时行为跟踪与高速摄像将
结合以评估由Trpv 1-伤害感受器的直接激活诱导的行为反应
(热感应)或Aδ LTMR(机械感应)。诱发行为的变化将在以下情况下进行评估
任何一种神经元群体的敏化以及选择性抑制外周CaV的潜力
通道来衰减这些输出。目的2研究神经细胞内钙动力学
皮肤中与超敏反应发展相关的末梢。光遗传学集成,双光子
体内钙成像和药理学将揭示CaV2.2和CaV3.2的单独贡献
Trpv 1-伤害感受器和Aδ LTMR中触发超敏反应的钙离子通道。这项工作
将提供关于外周CaV通道在诱导超敏反应中的作用的独特数据,
可以确定新的作用位点,用于开发更有效的疼痛治疗剂,从而减少
中枢神经系统的副作用。拟议的研究建立在
申请人的经验,并提供了一个机会,发展独特的专业知识,在遗传,行为,2-
光子成像和计算技术。与Fleischmann和摩尔实验室合作,
光子钙成像为申请人提供了团队科学和跨学科整合的重要经验。
不同层次的调查。该奖学金还将支持申请人的专业发展
严格的科学方法和有效的科学交流。脑科学环境
布朗大学是特殊的培训,它提供了许多途径的支持,培训,
为申请人作为独立学术科学家的职业生涯做准备的资源。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Remy Meir其他文献
Remy Meir的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
How Spinal Afferent Neurons Control Appetite and Thirst
脊髓传入神经元如何控制食欲和口渴
- 批准号:
DP220100070 - 财政年份:2023
- 资助金额:
$ 4.77万 - 项目类别:
Discovery Projects
The mechanisms of the signal transduction from brown adipocytes to afferent neurons and its significance.
棕色脂肪细胞向传入神经元的信号转导机制及其意义。
- 批准号:
23K05594 - 财政年份:2023
- 资助金额:
$ 4.77万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
- 批准号:
10477437 - 财政年份:2021
- 资助金额:
$ 4.77万 - 项目类别:
GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
- 批准号:
10315571 - 财政年份:2021
- 资助金额:
$ 4.77万 - 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
- 批准号:
10680037 - 财政年份:2021
- 资助金额:
$ 4.77万 - 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
- 批准号:
10654779 - 财政年份:2021
- 资助金额:
$ 4.77万 - 项目类别:
Neurobiology of Intrinsic Primary Afferent Neurons
内在初级传入神经元的神经生物学
- 批准号:
10275133 - 财政年份:2021
- 资助金额:
$ 4.77万 - 项目类别:
GPR35 on Vagal Afferent Neurons as a Peripheral Drug Target for Treating Diet-Induced Obesity
迷走神经传入神经元上的 GPR35 作为治疗饮食引起的肥胖的外周药物靶点
- 批准号:
10470747 - 财政年份:2021
- 资助金额:
$ 4.77万 - 项目类别:
Roles of mechanosensory ion channels in myenteric intrinsic primary afferent neurons
机械感觉离子通道在肌间固有初级传入神经元中的作用
- 批准号:
RGPIN-2014-05517 - 财政年份:2018
- 资助金额:
$ 4.77万 - 项目类别:
Discovery Grants Program - Individual
Roles of mechanosensory ion channels in myenteric intrinsic primary afferent neurons
机械感觉离子通道在肌间固有初级传入神经元中的作用
- 批准号:
RGPIN-2014-05517 - 财政年份:2017
- 资助金额:
$ 4.77万 - 项目类别:
Discovery Grants Program - Individual