Hyaluronan signaling to nociceptors in inflammatory pain
炎症性疼痛中透明质酸向伤害感受器发出信号
基本信息
- 批准号:10339337
- 负责人:
- 金额:$ 61.73万
- 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:2019-04-05 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:Absence of pain sensationAcute PainAffectAfferent NeuronsAnalgesicsApplications GrantsArthritisAttenuatedBindingBradykininCD44 AntigensCD44 geneCapsaicinCell membraneClinicalConnective Tissue DiseasesCutaneousDegenerative polyarthritisDermatitisDevelopmentDiseaseDoseElectrophysiology (science)ElementsExtracellular MatrixFiberFunctional disorderHyaluronanHyperalgesiaIn VitroInflammationInflammation MediatorsInflammatoryInjuryIntra-Articular InjectionsIon ChannelJointsLigandsMechanicsMediatingMethodsModalityMolecular WeightMovementNerveNerve EndingsNeuronsNeuropathyNociceptionNociceptorsPainPain ResearchPain managementPatientsPlayPopulationPre-Clinical ModelPropertyPublicationsReactive Oxygen SpeciesReportingResearchRoleSecond Messenger SystemsSignal PathwaySignal TransductionSpinal GangliaStressSupporting CellSyndromeSynovial jointTRPV1 geneTestingTherapeuticTissuesUrateattenuationbasechronic painclinical painexperimental studyimprovedin vivoinflammatory paininsightjoint inflammationknock-downmechanical forcenovelosteoarthritis painpain modelpain reductionpatch clamprational designreceptorsexual dimorphismtissue injuryviscoelasticityvoltage clamp
项目摘要
PROJECT SUMMARY/ABSTRACT
The extracellular matrix (ECM) plays a major role in the pathophysiology of painful connective tissue diseases
characterized by inflammation and tissue injury, such as arthritis and dermatitis. High molecular weight
hyaluronan (HMWH), the major non-protein component of the ECM, is metabolized to low molecular weight
hyaluronans (LMWH) in these clinical conditions. In preliminary studies we have shown that LMWH sensitizes
synovial and cutaneous nociceptors, and produces articular and cutaneous mechanical hyperalgesia. In contrast,
HMWH is currently used in the treatment of pain in patients with arthritis and other connective tissue diseases,
and while current dogma teaches that the analgesic properties of HMWH are due to its viscoelastic properties,
we propose the novel hypothesis that both HMWH-induced analgesia/anti-hyperalgesia, and LMWH-induced
mechanical hyperalgesia are both generated by their action at the cognate hyaluronan (HA) receptor, CD44, in
the plasma membrane of pain sensory neurons (nociceptors). To test this hypothesis, we will: 1)
comprehensively study the pro- and anti-nociceptive properties of these two size classes of HA to establish the
properties of LMWH that induce pain (hyperalgesia) and HMWH that induce analgesia (anti-hyperalgesia); 2)
use in vitro patch-clamp electrophysiology to establish that HA acts directly on nociceptors to sensitize (LMWH)
or reverse sensitization (HMWH) of nociceptor excitability, and determine the nociceptor populations upon which
HAs act to produce their effects and the ion channels in each population whose function is modulated by HA; 3)
confirm the role of the cognate hyaluronan receptor, CD44 and its downstream second messenger signaling
pathways, in LMWH hyperalgesia and HMWH analgesia, and that the CD44 is in nociceptors; and, 4) use
preclinical models of inflammatory, neuropathic and stress-induced pain to demonstrate that nociceptor CD44 is
involved in the pain in with these syndromes, and that HMWH can be used as an anti-hyperalgesia/analgesia
therapeutic modality. The proposed experiments will provide insight into the role of an important element of the
ECM in diverse pain syndromes, and a rationale for developing new, more effective forms of HMWH to treat
pain.
项目总结/文摘
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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JON DAVID LEVINE其他文献
JON DAVID LEVINE的其他文献
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{{ truncateString('JON DAVID LEVINE', 18)}}的其他基金
Hyaluronan signaling to nociceptors in inflammatory pain
炎症性疼痛中透明质酸向伤害感受器发出信号
- 批准号:
10558628 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Chronic Chemotherapy Peripheral Neuropathy: Role of Neuroplasticity and Stress
慢性化疗周围神经病变:神经可塑性和压力的作用
- 批准号:
10472499 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Hyaluronan signaling to nociceptors in inflammatory pain
炎症性疼痛中透明质酸向伤害感受器发出信号
- 批准号:
10091973 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Chronic Chemotherapy Peripheral Neuropathy: Role of Neuroplasticity and Stress
慢性化疗周围神经病变:神经可塑性和压力的作用
- 批准号:
10229396 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Hyaluronan signaling to nociceptors in inflammatory pain
炎症性疼痛中透明质酸向伤害感受器发出信号
- 批准号:
9750359 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Chronic Chemotherapy Peripheral Neuropathy: Role of Neuroplasticity and Stress
慢性化疗周围神经病变:神经可塑性和压力的作用
- 批准号:
10013159 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Chronic Chemotherapy Peripheral Neuropathy: Role of Neuroplasticity and Stress
慢性化疗周围神经病变:神经可塑性和压力的作用
- 批准号:
10701692 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Chronic Chemotherapy Peripheral Neuropathy: Role of Neuroplasticity and Stress
慢性化疗周围神经病变:神经可塑性和压力的作用
- 批准号:
9986945 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Hyaluronan signaling to nociceptors in inflammatory pain
炎症性疼痛中透明质酸向伤害感受器发出信号
- 批准号:
9908043 - 财政年份:2019
- 资助金额:
$ 61.73万 - 项目类别:
Nociceptor mechanisms in the transition from acute to chronic pain
从急性疼痛转变为慢性疼痛的伤害感受器机制
- 批准号:
8827433 - 财政年份:2014
- 资助金额:
$ 61.73万 - 项目类别:
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