Regulation of TRPV1 Activities by a Sexually Dimorphic Mechanism

性二态机制对 TRPV1 活性的调节

基本信息

项目摘要

Numerous studies indicate that women and men differ in prevalence of pain disorders or pain intensity, possibly due to sexually dimorphic differences in detection, processing or responses to noxious stimuli. Here, we propose to study a peripheral sexually dimorphic pain mechanism that occurs in humans. The importance of this complex problem has been emphasized by recent NIH policies (NOT OD 15-102). The objective here is to determine the effects of serotonin (5HT), applied to dental pulp biopsies from women versus men, on activation of capsaicin-sensitive nociceptors, and the mechanisms mediating this response. Our central hypothesis is that 5-HT preferentially releases complement peptides C3a or C5a from peripheral tissues of women compared to men, leading to a sexually dimorphic increase in TRPV1 activities in trigeminal (TG) sensory neurons. This central hypothesis is based on substantial novel preliminary data demonstrating that 5HT produces a sexually dimorphic difference in capsaicin activation of human peptidergic fibers via release of complement peptides. The Aims will: Specific Aim #1: Determine the cell type expressing C3a, C5a, C3aR, & C5aR in female versus male human dental pulp. Additional studies will determine the effects of inflammation (irreversible pulpitis) on expression and release of C3a and C5a from female and male human tissues. Specific Aim #2: Determine the 5-HT receptor subtype(s) and G-protein and effector signaling pathways mediating 5-HT-evoked release of C3a and C5a from female and male human tissues. Specific Aim #3: Determine the receptors, G-protein and effector signaling pathways mediating C3a-and C5a-evoked increase in activities of capsaicin-sensitive neurons. The central hypothesis is highly innovative and, if supported, would have an important positive impact on the field since it supports a new model for sexually dimorphic pain mechanisms with therapeutic implications. Moreover, the use of isolated human tissue biopsies and primary neuronal cultures fosters studies on the cellular mechanisms mediating this sexually dimorphic effect and increases translational significance.
许多研究表明,女性和男性在疼痛障碍的患病率或疼痛强度方面存在差异,

项目成果

期刊论文数量(0)
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Kenneth M Hargreaves其他文献

A Retrospective Study Comparing Clinical Outcomes after Obturation with Resilon/epiphany or Gutta-percha/kerr Sealer Comparison of Clinical Outcomes after Obturation with Resilon/epiphany Or
比较 Resilon/epiphany 或 Gutta-percha/kerr Sealer 充填后临床结果的回顾性研究 Resilon/epiphany 或 Gutta-percha/kerr 封闭剂充填后临床结果的比较
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Taylor P Cotton;William G Schindler;S. Schwartz;William R Watson;Kenneth M Hargreaves;De;Gutta;Kerr Sealer
  • 通讯作者:
    Kerr Sealer

Kenneth M Hargreaves的其他文献

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{{ truncateString('Kenneth M Hargreaves', 18)}}的其他基金

Mechanisms for Omega-6 Modulation of Primary Afferent Nociceptors
Omega-6 调节初级传入伤害感受器的机制
  • 批准号:
    10019608
  • 财政年份:
    2019
  • 资助金额:
    $ 38.13万
  • 项目类别:
Mechanisms for Omega-6 Modulation of Primary Afferent Nociceptors
Omega-6 调节初级传入伤害感受器的机制
  • 批准号:
    10242063
  • 财政年份:
    2019
  • 资助金额:
    $ 38.13万
  • 项目类别:
Mechanisms for Omega-6 Modulation of Primary Afferent Nociceptors
Omega-6 调节初级传入伤害感受器的机制
  • 批准号:
    9897012
  • 财政年份:
    2019
  • 资助金额:
    $ 38.13万
  • 项目类别:
Mechanisms for Omega-6 Modulation of Primary Afferent Nociceptors
Omega-6 调节初级传入伤害感受器的机制
  • 批准号:
    10472625
  • 财政年份:
    2019
  • 资助金额:
    $ 38.13万
  • 项目类别:
Craniofacial Oral-biology Student Training in Academic Research (COSTAR)
颅面口腔生物学学生学术研究培训(COSTAR)
  • 批准号:
    10197879
  • 财政年份:
    2018
  • 资助金额:
    $ 38.13万
  • 项目类别:
Craniofacial Oral-biology Student Training in Academic Research (COSTAR)
颅面口腔生物学学生学术研究培训(COSTAR)
  • 批准号:
    10424431
  • 财政年份:
    2018
  • 资助金额:
    $ 38.13万
  • 项目类别:
Evaluation of Endogenous TRP Agonists in Human Burns
内源性 TRP 激动剂在人体烧伤中的评价
  • 批准号:
    8631316
  • 财政年份:
    2014
  • 资助金额:
    $ 38.13万
  • 项目类别:
Evaluation of Endogenous TRP Agonists in Human Burns
内源性 TRP 激动剂在人体烧伤中的评价
  • 批准号:
    9178073
  • 财政年份:
    2014
  • 资助金额:
    $ 38.13万
  • 项目类别:
REGENERATION OF PULP-DENTIN DEVELOPMENT IN IMMATURE PERMANENT TEETH WITH NECROSIS
坏死的未成熟恒牙牙髓牙本质发育的再生
  • 批准号:
    7876114
  • 财政年份:
    2010
  • 资助金额:
    $ 38.13万
  • 项目类别:
Role of Oxidized Linoleic Acid Metabolites in Pain
氧化亚油酸代谢物在疼痛中的作用
  • 批准号:
    8032353
  • 财政年份:
    2010
  • 资助金额:
    $ 38.13万
  • 项目类别:

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脊髓传入神经元如何控制食欲和口渴
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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
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Neurobiology of Intrinsic Primary Afferent Neurons
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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
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