The Role of Testosterone on Mediating Sex and Gender Influences on Chronic Orofacial Pain Conditions

睾酮在调节性别和性别对慢性口面部疼痛的影响中的作用

基本信息

项目摘要

ABSTRACT AND PROJECT SUMMARY Many chronic pain conditions that affect craniofacial regions, such as temporomandibular disorders (TMD), disproportionately affect females. A growing number of studies show strong evidence that sex-related differences in conditioned pain modulation (CPM), a psychophysical index of endogenous pain inhibition, is one mechanism that predisposes women to an increased risk of chronic pain conditions. However, the central mechanisms underlying gender differences in CPM, as well as causal links between dysfunctional CPM and chronic orofacial pain conditions, are largely unknown. Our prior work has shown that there are sex differences in descending noxious inhibitory control (DNIC), a measure that is similar to CPM in preclinical settings, and that DNIC is modulated in a testosterone (TS)-dependent manner. The efficiency of DNIC was stronger in males compared to females. A pharmacological blockade of androgen receptors attenuated DNIC in males, and TS replacement enhanced DNIC in female rats. We also provided compelling evidence that the efficient DNIC in males is associated with a stronger resting functional connectivity between the rostral anterior cingulate cortex (rACC) and the periaqueductal gray (PAG). These observations provide a strong rationale for investigating the impact of TS on central pain modulation, and they also have significant clinical implications for pain management for both transgender and cisgender individuals undergoing hormone therapy. In this project, we will investigate the role of TS in maintaining efficient DNIC, as well as the mechanistic links between dysfunctional DNIC, TMD-like pain, and TMD-related comorbid pain conditions. Specifically, we hypothesize that the rACC to PAG circuit mediates sex differences in DNIC efficiency in a TS-dependent manner and that strengthening DNIC effectively attenuates TMD-related primary and comorbid pain responses. In specific aim (SA) 1, we will determine the role of the rACC to PAG circuit in DNIC efficiency using a behavioral paradigm and chemogenetics, which will experimentally manipulate the strength of the circuit with and without anti-androgen treatment in males and with and without TS treatment in females. In SA2, we will investigate the relationship between DNIC and TMD-like pain responses. We will conduct a concurrent functional magnetic resonance imaging (fMRI) to assess pain- induced changes in brain networks and confirm that both TS treatment and strengthening the rACC to PAG circuit rectify the pain-induced changes in the brain networks in male and female rats. In SA3, we will determine whether chemogenetically activating DNIC leads to a reduction in TMD-related comorbid pain responses and whether TS treatment further enhances the chemogenetic effects. The project will significantly improve our knowledge of the impact of sex on CNS pain modulation, which should have broad translational implications for the development of customized therapeutic strategies for both transgender and cisgender individuals.
摘要及项目总结

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 }}

Joyce Teixeira Da Silva其他文献

Joyce Teixeira Da Silva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 }}

{{ truncateString('Joyce Teixeira Da Silva', 18)}}的其他基金

Cerebral oscillations of pain
疼痛的大脑振荡
  • 批准号:
    10442525
  • 财政年份:
    2019
  • 资助金额:
    $ 47.14万
  • 项目类别:
Cerebral oscillations of pain
疼痛的大脑振荡
  • 批准号:
    10207807
  • 财政年份:
    2019
  • 资助金额:
    $ 47.14万
  • 项目类别:

相似海外基金

Androgen receptor: A master regulator of lipid metabolism
雄激素受体:脂质代谢的主要调节因子
  • 批准号:
    DP230103210
  • 财政年份:
    2023
  • 资助金额:
    $ 47.14万
  • 项目类别:
    Discovery Projects
Regulation of androgen receptor signaling in prostate cancer by protein arginine methylation
通过蛋白质精氨酸甲基化调节前列腺癌中的雄激素受体信号传导
  • 批准号:
    10584689
  • 财政年份:
    2023
  • 资助金额:
    $ 47.14万
  • 项目类别:
Structural and functional analysis of a novel class of androgen receptor antagonists
一类新型雄激素受体拮抗剂的结构和功能分析
  • 批准号:
    10650956
  • 财政年份:
    2023
  • 资助金额:
    $ 47.14万
  • 项目类别:
Role of the Androgen Receptor in Insulin Secretion in the Male
雄激素受体在男性胰岛素分泌中的作用
  • 批准号:
    10488954
  • 财政年份:
    2023
  • 资助金额:
    $ 47.14万
  • 项目类别:
Targeting tumor cell macrophage lipid interactions to overcome resistance to androgen receptor targeted therapy
靶向肿瘤细胞巨噬细胞脂质相互作用以克服对雄激素受体靶向治疗的耐药性
  • 批准号:
    10651105
  • 财政年份:
    2023
  • 资助金额:
    $ 47.14万
  • 项目类别:
Preclinical development of ONCT-505, an Androgen Receptor Antagonist and Degrader, as new potential therapeutic for Kennedy's Disease
ONCT-505(一种雄激素受体拮抗剂和降解剂)的临床前开发,作为肯尼迪病的新潜在治疗方法
  • 批准号:
    10603636
  • 财政年份:
    2023
  • 资助金额:
    $ 47.14万
  • 项目类别:
Androgen receptor function in melanoma
雄激素受体在黑色素瘤中的功能
  • 批准号:
    10416658
  • 财政年份:
    2022
  • 资助金额:
    $ 47.14万
  • 项目类别:
Proliferating cell nuclear antigen in regulation of androgen receptor signalings in castration-resistant prostate cancer cells
增殖细胞核抗原对去势抵抗性前列腺癌细胞雄激素受体信号传导的调节
  • 批准号:
    10544062
  • 财政年份:
    2022
  • 资助金额:
    $ 47.14万
  • 项目类别:
Effects of androgen receptor (AR) signaling on CD4+ T cell metabolism during airway inflammation
气道炎症期间雄激素受体 (AR) 信号对 CD4 T 细胞代谢的影响
  • 批准号:
    10534943
  • 财政年份:
    2022
  • 资助金额:
    $ 47.14万
  • 项目类别:
TITLE: BLADDER CANCER CHEMOPREVENTION USING THE ANDROGEN RECEPTOR INHIBITOR APALUTAMIDE
标题:使用雄激素受体抑制剂阿帕鲁胺进行膀胱癌化学预防
  • 批准号:
    10677989
  • 财政年份:
    2022
  • 资助金额:
    $ 47.14万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了