Identifying novel therapeutic targets for chronic neck pain: RNA-sequencing in human painful atlanto-axial arthropathy
确定慢性颈部疼痛的新治疗靶点:人类疼痛性寰枢椎关节病的 RNA 测序
基本信息
- 批准号:10684734
- 负责人:
- 金额:$ 58.31万
- 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:2021-09-01 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAcute PainArthritisAtlanto-Axial jointBilateralCell ProliferationCellsCervical spineCharacteristicsChronicChronic neck painClinicalComputational BiologyCoupledDataDatabasesDevelopmentDiseaseElectrophysiology (science)FractureFutureGenesGenetic TranscriptionGenomeGenomicsHealth ExpendituresHumanIndividualInfiltrationInflammatoryJointsKnowledgeLigandsLinkMacrophageMapsMeasuresMethodsModelingMolecularMolecular TargetNeckNeck PainNerveNerve TissueNervous SystemNeuronsNeurosciencesNociceptorsOperative Surgical ProceduresOrgan DonorPainPain MeasurementPainlessPathologicPathway interactionsPatient RecruitmentsPatientsPersonsPhenotypeResolutionSamplingSensorySideSignal TransductionSiteSpinal GangliaStimulusTechniquesTestingTherapeuticTissue SampleTissuesVertebral columnWorkarthropathiesburden of illnesschronic painchronic pain patientclinical paincohortdifferential expressiondisabilitydrug developmentinnovationinsightmolecular sequence databasenerve supplynew therapeutic targetopioid epidemicpain outcomepain patientpain sensitivitypain signalpainful neuropathypharmacologicpressureradicular painreceptorstemtranscriptometranscriptome sequencingtranscriptomics
项目摘要
PROJECT SUMMARY / ABSTRACT
Background. Chronic neck pain is one of leading determinants of disability worldwide, a major contributor to the
current opioid epidemic, and the cause of enormous health care expenditures. We currently do not understand
which molecular mechanisms in the diseased tissues of the neck generate the painful signals that cause this
disease burden. This gap in knowledge impedes development of effective, mechanism-specific therapeutics.
Aim. We plan to use RNA sequencing on tissues taken from chronic neck pain patients undergoing surgery and
then use computational biology and patient phenotyping techniques to gain better insight into molecular drivers
that cause chronic neck pain.
Approach. We will recruit patients undergoing surgery for chronic neck pain stemming from the atlanto-axial
joint. This joint is located between the 1st and 2nd cervical vertebrae on both sides of the spine and is a common
site of arthritis. We will also recruit patients undergoing the same surgery for acute pain due to fractures. During
surgery, we will sample tissues from the joint and the dorsal root ganglion (DRG), in which the nerves supplying
the joint are located. These tissues would be removed during surgery in chronic pain patients, independent of
the study. For acute pain patients we will use our existing dorsal root ganglion database of people with no pain.
We will perform RNA sequencing on samples from both sides, in order to compare tissues from painful and non-
painful side of the same individual. We will record clinical pain characteristics, measure pain sensitivity and
assess nerve function using pinprick, pressure and cold stimuli. We will also use computational biology methods
to assess how diseased tissue interacts with the nervous system to drive pain. These methods will allow us to
identify targets that are related to pain outcomes.
Aim 1: To determine the RNA expression profile of the joint tissues and DRG from acute and chronic pain
patients to determine genes that are differentially expressed in chronic neck pain tissues.
Aim 2: To use computational biology techniques to determine how pathological molecules originating in the joint
tissues interact with specific receptors on neurons of the DRG to generate the pain signal.
Aim 3: To determine the association of RNA sequencing findings in the joint and nerves with clinical
manifestations of neck pain, pain sensitivity and nerve function. This will provide information on which molecular
changes at the joint and nerves are of specific importance to pain.
Impact. The project will enable unprecedented identification of molecular pathways specifically associated with
chronic neck pain. Our work will create a unique map of molecular targets for the future treatment of chronic
neck pain based entirely on human molecular neuroscience.
项目摘要/摘要
背景资料。慢性颈痛是全球残疾的主要决定因素之一,是导致
目前阿片类药物的流行,以及医疗保健支出巨大的原因。我们目前还不明白
颈部病变组织中的哪些分子机制会产生导致这种疼痛的信号
疾病负担。这种知识上的差距阻碍了有效的、特定机制的疗法的发展。
瞄准。我们计划对接受手术和治疗的慢性颈痛患者的组织进行RNA测序
然后使用计算生物学和患者表型技术来更好地了解分子驱动因素
会导致慢性颈部疼痛。
接近。我们将招募因寰枢椎慢性颈痛而接受手术的患者。
联合。这个关节位于脊柱两侧的第一和第二颈椎之间,是一种常见的
关节炎的地点。我们还将招募因骨折引起的急性疼痛而接受相同手术的患者。在.期间
手术中,我们将从关节和背根节(DRG)取样组织,在背根节中,神经供应
关节已定位。这些组织将在慢性疼痛患者的手术过程中被移除,独立于
这项研究。对于急性疼痛患者,我们将使用我们现有的无疼痛患者的背根节数据库。
我们将对两侧的样本进行RNA测序,以比较疼痛和非疼痛的组织
同一个人痛苦的一面。我们将记录临床疼痛特征,测量疼痛敏感性和
用针刺、按压和冷刺激评估神经功能。我们还将使用计算生物学方法
以评估病变组织如何与神经系统相互作用来驱动疼痛。这些方法将使我们能够
确定与疼痛结果相关的目标。
目的1:测定急、慢性疼痛关节组织和背根节的RNA表达谱
患者需要确定在慢性颈痛组织中差异表达的基因。
目标2:使用计算生物学技术来确定病理分子如何起源于关节
组织与背根神经节神经元上的特定受体相互作用,产生疼痛信号。
目的3:确定关节和神经中的RNA测序结果与临床的关系
颈部疼痛、疼痛敏感和神经功能的表现。这将提供哪些分子的信息
关节和神经的变化对疼痛特别重要。
冲击力。该项目将使人们能够史无前例地识别与特定的
慢性颈痛。我们的工作将创建一个独特的分子靶点图谱,用于未来的慢性阻塞性肺疾病的治疗
颈部疼痛完全基于人类分子神经科学。
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)
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Michele Curatolo其他文献
Michele Curatolo的其他文献
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{{ truncateString('Michele Curatolo', 18)}}的其他基金
Early Phase Pain Investigation Clinical Network Hub at the University of Washington
华盛顿大学早期疼痛调查临床网络中心
- 批准号:
10903640 - 财政年份:2023
- 资助金额:
$ 58.31万 - 项目类别:
Human Nociceptor and Spinal Cord Molecular Signature Center
人类伤害感受器和脊髓分子特征中心
- 批准号:
10593656 - 财政年份:2022
- 资助金额:
$ 58.31万 - 项目类别:
Mechanistic underpinnings of chronic low back pain
慢性腰痛的机制基础
- 批准号:
10593659 - 财政年份:2022
- 资助金额:
$ 58.31万 - 项目类别:
Mechanistic underpinnings of chronic low back pain
慢性腰痛的机制基础
- 批准号:
10707549 - 财政年份:2022
- 资助金额:
$ 58.31万 - 项目类别:
Human Nociceptor and Spinal Cord Molecular Signature Center
人类伤害感受器和脊髓分子特征中心
- 批准号:
10707528 - 财政年份:2022
- 资助金额:
$ 58.31万 - 项目类别:
Human Nociceptor and Spinal Cord Molecular Signature Center
人类伤害感受器和脊髓分子特征中心
- 批准号:
10770232 - 财政年份:2022
- 资助金额:
$ 58.31万 - 项目类别:
Identifying novel therapeutic targets for chronic neck pain: RNA-sequencing in human painful atlanto-axial arthropathy
确定慢性颈部疼痛的新治疗靶点:人类疼痛性寰枢椎关节病的 RNA 测序
- 批准号:
10311697 - 财政年份:2021
- 资助金额:
$ 58.31万 - 项目类别:
Identifying novel therapeutic targets for chronic neck pain: RNA-sequencing in human painful atlanto-axial arthropathy
确定慢性颈部疼痛的新治疗靶点:人类疼痛性寰枢椎关节病的 RNA 测序
- 批准号:
10471940 - 财政年份:2021
- 资助金额:
$ 58.31万 - 项目类别:
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