BLR&D Research Career Scientist Award Application
BLR&D Research Career Scientist Award Application
批准号:
10046730
负责人:
Beverley Greenwood-Van Meerveld
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-10-01 至 2023-09-30
关键词:
Abdominal PainAddressAdultAdverse effectsAffectAmericanAmygdaloid structureAnxietyAreaAwardBasic ScienceBiologyBrainCaringChronicClinical SciencesCommunicationContractsCorticosteroneCorticotropin-Releasing HormoneDevelopmentDiagnosisDigestive System DisordersDiseaseDisease OutbreaksDown-RegulationElectrophysiology (science)EmotionalExhibitsExposure toExtramural ActivitiesFemaleFoundationsFunctional disorderFundingFutureGastroenterologyGastrointestinal tract structureGene ExpressionGene TargetingGenesGlucocorticoid ReceptorGoalsGrantGulf War veteranHCN1 channelHabitsHealthHealthcareHypersensitivityIleusIndustryIndustry CollaborationInflammatory Bowel DiseasesInternationalInterstitial CystitisIntestinesInvestigational TherapiesIrritable Bowel SyndromeJointsJournalsKnowledgeLaboratoriesLeadLeadershipLifeMediatingMethodsMilitary PersonnelMissionMolecularNeural PathwaysNeuraxisNeuronal PlasticityNeuronsNeuropharmacologyNeurosciencesNociceptionOklahomaOrganPainPathway interactionsPatient CarePatientsPharmacologyPostdoctoral FellowPostoperative PeriodPredispositionPresbyterian ChurchPrivatizationPsychiatryPublicationsReagentRecording of previous eventsRegulationReportingResearchResearch Project GrantsRiskRisk FactorsRodent ModelRoleScientific Advances and AccomplishmentsScientistServicesSex DifferencesSexual abuseSoldierSolidStressSymptomsSystemTechniquesUnited States Department of Veterans AffairsUnited States National Institutes of HealthUniversitiesVeteransVisceralVisceral painWomananxiety-like behaviorauthoritybehavioral pharmacologycareercell motilitychronic abdominal paincombatdesignearly life stresseditorialexperienceexperimental studygastrointestinalgraduate studenthypothalamic-pituitary-adrenal axisimprovedindustry partnerinnovationinsightinterestknock-downmilitary veteranneural circuitneuropsychopharmacologynew therapeutic targetnovelnovel therapeuticspain sensitivitypre-clinicalprogramsreceptorreceptor expressionrelating to nervous systemresearch and developmentresearch studyresilienceresponsestressorsymptomatologytargeted treatmentundergraduate student
中文摘要
项目总结/文摘
英文摘要
Project Summary/Abstract
My primary research interest focuses on the central nervous system regulation of visceral pain with a strategic
objective of using preclinical rodent models and multiple state-of-the-art techniques, from molecular and
cellular to behavioral, pharmacological and electrophysiological methods to advance basic scientific knowledge
that has direct relevance to the diagnosis and treatment of veterans with visceral pain. Below I have
summarized the main research projects in my laboratory.
1. Central Neural Circuitry Underlying Anxiety and Visceral pain: Mechanisms of Resilience and Novel
Treatments: In one aspect of my research we are studying the neuroanatomical and neuropharmacological
substrates involved in the interaction between visceral pain and anxiety. My research focuses on the role of
amygdala-mediated mechanisms in the control of visceral and somatic pain and the mechanisms connecting
anxiety and visceral (colonic) hypersensitivity. We are attempting to identify at least one potential neural
substrate that might be involved in the central processing of visceral pain. From there we hope to identify a
receptor mechanism within the neural substrate that mediates central processing of visceral pain. A long-term
goal is to investigate how the neural substrate modulates visceral pain sensitivity within the larger neural
pathway controlling anxiety, and use this knowledge to identify potential pharmacotherapeutic targets in the
central processing pathway that mediates visceral pain. We have demonstrated long lasting increases in
anxiety-like behavior and viscerosomatic sensitivity in response to the local exposure of the amygdala to
corticosterone (CORT). We found persistent down-regulation of GR expression and increases in the
expression of CRF and HCN1 channels leading to hyper-excitability of the CeA neurons. These changes in
gene expression represent a potential mechanism leading to chronic anxiety and pain, via facilitation of the
HPA axis. The objective of latest experiments has been to use gene knockdown to directly manipulate CRF
and GR expression in the central amygdala. We found that knockdown of CRF within the amygdala inhibits
stress-induced chronic visceral and somatic pain, and that loss of GR within the amygdala is key to triggering
visceral and somatic pain. Such findings are relevant for the future development of gene targeted therapeutics
to treat stress-induced visceral and somatic pain (Funded by the Department of Veteran's Affairs Merit Award:
2013-2017).
2. Early life stress on visceral and somatic pain in adulthood: Sex differences. In women, IBS is the most
prevalent GI disorders. Emotional stressors, increased anxiety or uni- and bipolar associative disorders often
exacerbate symptoms. Despite this knowledge and evidence that females embody strong connections to life
stressors, physical/sexual abuse and an emotionally reactive disposition related to the outbreak of
symptomatology, there has been very little progress made to enhance our understanding of the descending
connections between the brain and the GI tract in female Veterans. Our latest project was designed to
investigate the mechanisms by which the context of the early life stress (ELS) can affect nociception in
adulthood. We are also exploring evidence for a two hit hypothesis underlying the vulnerability to visceral pain
in females. Specifically, we will investigate the mechanisms by which an unpredictable stress in early life leads
to chronic abdominal pain in adulthood. Additionally we will assess the impact of ELS on the amygdala
response to an adult stressor (Funded by the Department of Veteran's Affairs Merit Award: 2010-2014; 2015-
2019).
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DOI:
10.1016/j.ynstr.2023.100590
发表时间:
2024-01
期刊:
NEUROBIOLOGY OF STRESS
影响因子:
5
作者:
[Orock, A., Johnson, A. C., Mohammadi, E., Meerveld, B. Greenwood-Van]
通讯作者:
Meerveld, B. Greenwood-Van
DOI:
10.3389/fnsys.2017.00086
发表时间:
2017
期刊:
Frontiers in systems neuroscience
影响因子:
3
作者:
[Greenwood-Van Meerveld B, Johnson AC]
通讯作者:
Johnson AC
DOI:
10.1002/jbm.b.33985
发表时间:
2018-07
期刊:
Journal of biomedical materials research. Part B, Applied biomaterials
影响因子:
--
作者:
[Qing Yang;D. Xia;R. Towner;N. Smith;D. Saunders;K. Fung;C. Aston;B. Greenwood-Van Meerveld;R. Hurst;S. Madihally;B. Kropp;Hsueh-Kung Lin]
通讯作者:
Qing Yang;D. Xia;R. Towner;N. Smith;D. Saunders;K. Fung;C. Aston;B. Greenwood-Van Meerveld;R. Hurst;S. Madihally;B. Kropp;Hsueh-Kung Lin
DOI:
10.1111/nmo.13500
发表时间:
2019-03
期刊:
Neurogastroenterology and motility
影响因子:
3.5
作者:
[Louwies T, Ligon CO, Johnson AC, Greenwood-Van Meerveld B]
通讯作者:
Greenwood-Van Meerveld B
DOI:
10.3389/fnins.2018.00543
发表时间:
2018
期刊:
Frontiers in neuroscience
影响因子:
4.3
作者:
[Hattay P, Prusator DK, Johnson AC, Greenwood-Van Meerveld B]
通讯作者:
Greenwood-Van Meerveld B
共 14 条
ShEEP Request for Leica BOND RX
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批准号:9796357
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项目类别:
-
资助金额:$0.0万
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财政年份:2019
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
BLR&D Research Career Scientist Award Application
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批准号:9231123
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项目类别:
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资助金额:$0.0万
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财政年份:2016
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
Central Mechanisms Modulating Visceral Sensitivity
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批准号:8543970
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项目类别:
-
资助金额:$0.0万
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财政年份:2013
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
Understanding Pain of Gastrointestinal Origin in Women that Serve in OEF/OIF
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批准号:9033203
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
Understanding Pain of Gastrointestinal Origin in Women that Serve in OEF/OIF
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批准号:8254312
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
Understanding Pain of Gastrointestinal Origin in Women that Serve in OEF/OIF
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批准号:9210532
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
Understanding Pain of Gastrointestinal Origin in Women that Serve in OEF/OIF
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批准号:8398974
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
Understanding Pain of Gastrointestinal Origin in Women that Serve in OEF/OIF
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批准号:8696838
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
Understanding Pain of Gastrointestinal Origin in Women that Serve in OEF/OIF
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批准号:8142489
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项目类别:
-
资助金额:$0.0万
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财政年份:2011
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负责人:Beverley Greenwood-Van Meerveld
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依托单位:
海外基金