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
基本信息
- 批准号:9763786
- 负责人:
- 金额:$ 21.87万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-10 至 2021-04-30
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAffectAlcohol abuseAlcohol consumptionAlcohol dependenceAlcohol withdrawal syndromeAlcoholsAmericanAnalgesicsAnimal ModelAttenuatedBehaviorBrainBrain regionChronicComorbidityCorticotropin-Releasing HormoneCoupledDangerousnessDataDevelopmentElectrophysiology (science)EmotionalEthanolFutureGlutamatesGoalsHeavy DrinkingHyperalgesiaIncidenceInvestigationMeasuresModelingMolecularMusNeuronsOutcomeOutputPainPain managementPathologicPathway interactionsPatientsPeriodicityPharmacologyPhysiologicalPopulationPropertyPublic HealthRecording of previous eventsRegulationResearchRoleScanningSignal TransductionSiteSliceStimulusStructure of terminal stria nuclei of preoptic regionTestingUnited StatesViralWithdrawalWorkalcohol behavioralcohol exposurealcohol use disorderchronic alcohol ingestionchronic painchronic pain patientdisabilitydopaminergic neuroneffective therapyexperimental studyin vivoin vivo calcium imaginginsightinterestmalemembrane-associated placental tissue protein 1midbrain central gray substanceneuronal circuitryneurotransmissionnoveloptogeneticspain reductionpain reliefpain sensitivityrecruitside effectstemtransmission process
项目摘要
The high incidence of alcohol abuse that occurs in patients with chronic pain underscores the importance of
continued research towards effective treatments for both pain and alcohol use disorders. It has been found in
animal models that chronic alcohol exposure can drive adaptations in the brain, which drive increased pain-
related behaviors. Our long-term goal is to understand how chronic alcohol exposure can alter the neuronal
circuits that regulate pain-related behavior in order to develop more effective approaches to treat alcohol induced
pain. One region of particular interest for these studies is the periaqueductal gray (PAG). We have previously
shown that a subpopulation of dopamine neurons in the ventrolateral PAG (PAGDA) are activated by acute alcohol
and activation of these same neurons induces an anti-nociceptive effect in the hot-plate test. Furthermore, in
our preliminary data, we found that activation of the outputs to the bed nucleus of the stria terminalis (BNST)
could replicate this anti-nociceptive effect. These findings are noteworthy, as they identify a novel ascending
anti-nociceptive pathway (PAGDA to BNST) distinct from the well-characterized descending anti-nociceptive
pathway (PAG to Medulla). In keeping with the critical role of the PAGDA to BNST pathway, we found that viral
deletion of CRF from the BNST can alter pain related behaviors. In addition, we have found that intermittent
alcohol drinking can drive changes in pain-related behavior in mice. Taken together, these studies support the
testable hypothesis that intermittent alcohol drinking drives alterations in pain related behavior, in part through
disruptions in the PAGDA to BNST pathway, and that in vivo activation of this pathway can ameliorate alcohol-
induced hyperalgesia.
慢性疼痛患者酗酒的高发病率强调了以下方面的重要性:
继续研究对疼痛和酒精使用障碍的有效治疗方法。已经发现
动物模型表明,慢性酒精暴露可以驱动大脑的适应性,从而增加疼痛,
相关行为。我们的长期目标是了解慢性酒精暴露如何改变神经元的功能。
调节疼痛相关行为的回路,以开发更有效的方法来治疗酒精诱导的
痛苦这些研究中特别感兴趣的一个区域是中脑导水管周围灰质(PAG)。我们先前已经
表明急性酒精激活腹外侧PAG(PAGDA)中的多巴胺神经元亚群
并且这些相同神经元的激活在热板试验中诱导抗伤害感受效应。更以
我们的初步数据,我们发现,激活输出到床核的终纹(BNST)
可以复制这种抗伤害效应。这些发现是值得注意的,因为他们确定了一个新的提升,
抗伤害性通路(PAGDA至BNST),不同于特征明确的下行抗伤害性通路
途径(PAG到髓质)。与PAGDA到BNST通路的关键作用一致,我们发现病毒
从BNST中删除CRF可以改变疼痛相关行为。此外,我们还发现,
饮酒可以改变小鼠的疼痛相关行为。总之,这些研究支持了
间歇性饮酒会导致疼痛相关行为的改变,部分原因是
PAGDA到BNST通路的中断,并且该通路的体内激活可以改善酒精-
诱发痛觉过敏
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
A distinct cortical code for socially learned threat
用于社会学习到的威胁的一种独特皮质编码
- DOI:
10.1038/s41586-023-07008-1 - 发表时间:
2024-02-07 - 期刊:
- 影响因子:48.500
- 作者:
Shana E. Silverstein;Ruairi O’Sullivan;Olena Bukalo;Dipanwita Pati;Julia A. Schaffer;Aaron Limoges;Leo Zsembik;Takayuki Yoshida;John J. O’Malley;Ronald F. Paletzki;Abby G. Lieberman;Mio Nonaka;Karl Deisseroth;Charles R. Gerfen;Mario A. Penzo;Thomas L. Kash;Andrew Holmes - 通讯作者:
Andrew Holmes
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:
$ 21.87万 - 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:
10386925 - 财政年份:2021
- 资助金额:
$ 21.87万 - 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:
$ 21.87万 - 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:
$ 21.87万 - 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:
$ 21.87万 - 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:
$ 21.87万 - 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:
$ 21.87万 - 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:
$ 21.87万 - 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:
$ 21.87万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 21.87万 - 项目类别:
Research Grant