Determining the impact of BNST CRF systems on inflammatory pain-induced disruptions of behavior

确定 BNST CRF 系统对炎性疼痛引起的行为破坏的影响

基本信息

  • 批准号:
    10386925
  • 负责人:
  • 金额:
    $ 41.73万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-04-15 至 2026-03-31
  • 项目状态:
    未结题

项目摘要

Pain is currently the most common cause of long-term disability in the United States, affecting over 70 million Americans and 1.5 billion people worldwide. The first line of treatment for pain has been opioids, however their use is associated with addiction, dependence and overdose. A strategy for reducing the reliance on opioids for treatment of chronic pain is to better understand the circuits that mediate different aspects of chronic pain and identify non-opioidergic mechanisms to restore normal circuit function and behavior. Corticotropin releasing factor (CRF) signaling in the bed nucleus of the stria terminalis (BNST) has been shown to regulate both nociceptive and affective/motivational behaviors associated with pain, however the clinical utility of pharmacologically targeting the CRF system has yet to be explored. Given the critical need to develop treatments to target affective and motivational aspects of chronic pain, this could be an important path forward. We hypothesize that persistent inflammatory pain leads to increased activation of CRF signaling in the BNST leading to disrupted affective behaviors and reduced motivation. We posit that modulators of BNST function that oppose CRF signaling could provide a novel approach to investigate and treat both nociceptive and motivational/affective aspects of pain. Relevant to this, we have found in preliminary studies, a population of periaqueductal gray dopamine (PAGDA) neurons that project to the BNST that exhibit anti-nociceptive properties when activated, highlighting the possibility that dopamine in the BNST is a critical suppressor of pain-related behaviors. Previous studies have found that these PAGDA neurons play a key role in opioid induced anti-nociception. The objective of this proposal is to rigorously and mechanistically determine the role of the PAGDA to BNSTCRF circuit in inflammatory pain-driven changes in behavior, with the long term goal of identifying new treatments for inflammatory pain. We have collected strong data showing that acute pain engages this circuit, and hypothesize that this initial engagement leads to plasticity contributing to the persistence of inflammatory pain, and the development of emotional behaviors associated with inflammatory pain. This will be accomplished via three convergent aims
疼痛是目前美国长期残疾的最常见原因,影响超过7000万人。 美国人和全世界15亿人。治疗疼痛的第一线药物是阿片类药物,但 吸毒与成瘾、依赖和过量有关。减少对阿片依赖的战略 慢性疼痛的治疗是为了更好地了解介导慢性疼痛不同方面的电路, 识别非阿片样物质机制以恢复正常回路功能和行为。皮质激素释放 终纹床核(BNST)中的促肾上腺皮质激素释放因子(CRF)信号转导已被证明可调节这两种作用。 与疼痛相关的伤害性和情感/动机行为,然而, 以通用报告格式系统为目标的改革尚待探索。鉴于开发治疗方法的迫切需要 为了针对慢性疼痛的情感和动机方面,这可能是一条重要的前进道路。我们 假设持续性炎性疼痛导致BNST中CRF信号的激活增加, 情感行为中断和动机降低。我们认为BNST功能的调节剂, CRF信号可能为研究和治疗伤害性和动机/情感性提供新的途径 疼痛的方面。与此相关的是,我们在初步研究中发现, 投射到BNST的多巴胺(PAGDA)神经元,其在激活时表现出抗伤害感受特性, 强调了BNST中的多巴胺是疼痛相关行为的关键抑制剂的可能性。先前 研究发现这些PAGDA神经元在阿片样物质诱导的抗伤害感受中起关键作用。客观 这一建议的目的是严格和机械地确定PAGDA到BNSTCRF电路的作用, 炎症疼痛驱动的行为变化,长期目标是确定新的治疗方法, 炎性疼痛。我们已经收集了强有力的数据,表明急性疼痛涉及这个回路,并假设 这种最初的参与导致了可塑性,有助于炎症性疼痛的持续, 与炎性疼痛相关的情绪行为的发展。这将通过三个 趋同目标

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 }}

Thomas L. Kash其他文献

Withdrawal from chronic intermittent ethanol engages a circuit in the bed nucleus of the stria terminalis that promotes anxiety and fear-related behavior
  • DOI:
    10.1016/j.alcohol.2017.02.354
  • 发表时间:
    2017-05-01
  • 期刊:
  • 影响因子:
  • 作者:
    Catherine A. Marcinkiewcz;Dipanwita Pati;Jeffrey F. Diberto;Thomas L. Kash
  • 通讯作者:
    Thomas L. Kash
A dual-virus strategy for the deletion of cacan1c within the prelimbic to nucleus accumbens core projection
用于在前边缘至伏隔核核心投射内删除 cacan1c 的双病毒策略
  • DOI:
    10.1038/s41380-020-00886-1
  • 发表时间:
    2020-09-24
  • 期刊:
  • 影响因子:
    10.100
  • 作者:
    Charlotte C. Bavley;Robert N. Fetcho;Caitlin E. Burgdorf;Alexander P. Walsh;Delaney K. Fischer;Baila S. Hall;Nicole M. Sayles;Natalina H. Contoreggi;Jonathan E. Hackett;Susan A. Antigua;Rachel Babij;Natalia V. De Marco García;Thomas L. Kash;Teresa A. Milner;Conor Liston;Anjali M. Rajadhyaksha
  • 通讯作者:
    Anjali M. Rajadhyaksha
Corticotropin-Releasing Factor Modulates Binge-Like Ethanol Drinking in a Sex-Dependent Manner: Impact of Amygdala Deletion and Inhibition of a Central Amygdala to Lateral Hypothalamus Circuit
  • DOI:
    10.1016/j.bpsgos.2024.100405
  • 发表时间:
    2025-01-01
  • 期刊:
  • 影响因子:
  • 作者:
    Sophie C. Bendrath;Hernán G. Méndez;Anne M. Dankert;Jose Manuel Lerma-Cabrera;Francisca Carvajal;Ana Paula S. Dornellas;Sophia Lee;Sofia Neira;Harold Haun;Eric Delpire;Montserrat Navarro;Thomas L. Kash;Todd E. Thiele
  • 通讯作者:
    Todd E. Thiele
RETRACTED ARTICLE: Predator odor increases avoidance and glutamatergic synaptic transmission in the prelimbic cortex via corticotropin-releasing factor receptor 1 signaling
撤回文章:捕食者气味通过促肾上腺皮质激素释放因子受体 1 信号通路增加前边缘皮层的回避行为和谷氨酸能突触传递
  • DOI:
    10.1038/s41386-018-0279-2
  • 发表时间:
    2018-11-23
  • 期刊:
  • 影响因子:
    7.100
  • 作者:
    Lara S. Hwa;Sofia Neira;Melanie M. Pina;Dipanwita Pati;Rachel Calloway;Thomas L. Kash
  • 通讯作者:
    Thomas L. Kash
Review for "Integrating the monoamine and cytokine hypotheses of depression: Is histamine the missing link?"
评论“整合抑郁症的单胺和细胞因子假说:组胺是缺失的一环吗?”
  • DOI:
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Thomas L. Kash
  • 通讯作者:
    Thomas L. Kash

Thomas L. Kash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('Thomas L. Kash', 18)}}的其他基金

Dietary choline mitigation of adolescent alcohol-induced deficits in adult cognitive flexibility: P60-AA011605 Administrative Supplement
膳食胆碱缓解青少年酒精引起的成人认知灵活性缺陷:P60-AA011605 行政补充
  • 批准号:
    10330051
  • 财政年份:
    2021
  • 资助金额:
    $ 41.73万
  • 项目类别:
Determining the impact of BNST CRF systems on inflammatory pain-induced disruptions of behavior
确定 BNST CRF 系统对炎性疼痛引起的行为破坏的影响
  • 批准号:
    10608985
  • 财政年份:
    2021
  • 资助金额:
    $ 41.73万
  • 项目类别:
2019 Amygdala Function in Emotion, Cognition and Disease GRS/GRC
2019 杏仁核在情绪、认知和疾病中的功能 GRS/GRC
  • 批准号:
    9758948
  • 财政年份:
    2019
  • 资助金额:
    $ 41.73万
  • 项目类别:
Dissecting the role of ethanol-induced plasticity in the PAG to BNST pathway in pain-related behaviors
剖析乙醇诱导的可塑性在 PAG 至 BNST 通路中在疼痛相关行为中的作用
  • 批准号:
    9763786
  • 财政年份:
    2019
  • 资助金额:
    $ 41.73万
  • 项目类别:
Dissecting the role of ethanol-induced plasticity in the PAG to BNST pathway in pain-related behaviors
剖析乙醇诱导的可塑性在 PAG 至 BNST 通路中在疼痛相关行为中的作用
  • 批准号:
    9926793
  • 财政年份:
    2019
  • 资助金额:
    $ 41.73万
  • 项目类别:
Core 1: Brain Circuit Validation Core
核心1:脑回路验证核心
  • 批准号:
    10090540
  • 财政年份:
    2017
  • 资助金额:
    $ 41.73万
  • 项目类别:
The role of corticotropin releasing factor in binge-like ethanol drinking
促肾上腺皮质激素释放因子在酗酒中的作用
  • 批准号:
    10444006
  • 财政年份:
    2013
  • 资助金额:
    $ 41.73万
  • 项目类别:
The role of corticotropin releasing factor in binge-like ethanol drinking
促肾上腺皮质激素释放因子在酗酒中的作用
  • 批准号:
    10600068
  • 财政年份:
    2013
  • 资助金额:
    $ 41.73万
  • 项目类别:
Chronic Alcohol Induced Dysregulation of Central Anti-Stress Systems
慢性酒精引起中枢抗应激系统失调
  • 批准号:
    8423705
  • 财政年份:
    2012
  • 资助金额:
    $ 41.73万
  • 项目类别:
5/8 INIA Stress and Chronic Alcohol Interactions: Probing brain circuits that regulate alcohol stress interactions
5/8 INIA 压力和慢性酒精相互作用:探索调节酒精压力相互作用的大脑回路
  • 批准号:
    10574573
  • 财政年份:
    2012
  • 资助金额:
    $ 41.73万
  • 项目类别:

相似海外基金

Clinical Outcome Assessments for Acute Pain Therapeutics in Infants and young Children (COA APTIC)
婴幼儿急性疼痛治疗的临床结果评估 (COA APTIC)
  • 批准号:
    10778757
  • 财政年份:
    2023
  • 资助金额:
    $ 41.73万
  • 项目类别:
Selective actin remodeling of sensory neurons for acute pain management
感觉神经元的选择性肌动蛋白重塑用于急性疼痛管理
  • 批准号:
    10603436
  • 财政年份:
    2023
  • 资助金额:
    $ 41.73万
  • 项目类别:
Clinical Outcome Assessments for Acute Pain Therapeutics in Infants and young Children (COA APTIC)
婴幼儿急性疼痛治疗的临床结果评估 (COA APTIC)
  • 批准号:
    10783106
  • 财政年份:
    2023
  • 资助金额:
    $ 41.73万
  • 项目类别:
Development of A Focused Ultrasound Device for Noninvasive, Peripheral Nerve Blockade to Manage Acute Pain
开发用于非侵入性周围神经阻断来治疗急性疼痛的聚焦超声装置
  • 批准号:
    10740796
  • 财政年份:
    2023
  • 资助金额:
    $ 41.73万
  • 项目类别:
Predicting Pediatric Sickle Cell Disease Acute Pain Using Mathematical Models Based on mHealth Data
使用基于移动健康数据的数学模型预测儿童镰状细胞病急性疼痛
  • 批准号:
    10599401
  • 财政年份:
    2022
  • 资助金额:
    $ 41.73万
  • 项目类别:
Non-Contingent Acute Pain Stress Drives Analgesic Protection in Rats.
非偶然急性疼痛应激驱动大鼠镇痛保护。
  • 批准号:
    575854-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 41.73万
  • 项目类别:
    Alexander Graham Bell Canada Graduate Scholarships - Master's
Prefrontal Cortex Hemodynamic Responses to Mindfulness Meditation and Acute Pain
前额皮质血流动力学对正念冥想和急性疼痛的反应
  • 批准号:
    467076
  • 财政年份:
    2021
  • 资助金额:
    $ 41.73万
  • 项目类别:
    Studentship Programs
A Multimodal Approach for Monitoring Prolonged Acute Pain in Neonates
监测新生儿长期急性疼痛的多模式方法
  • 批准号:
    9979265
  • 财政年份:
    2020
  • 资助金额:
    $ 41.73万
  • 项目类别:
Endocannabinoid Metabolism in Acute Pain
急性疼痛中的内源性大麻素代谢
  • 批准号:
    10356880
  • 财政年份:
    2020
  • 资助金额:
    $ 41.73万
  • 项目类别:
A Multimodal Approach for Monitoring Prolonged Acute Pain in Neonates
监测新生儿长期急性疼痛的多模式方法
  • 批准号:
    10218273
  • 财政年份:
    2020
  • 资助金额:
    $ 41.73万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了