Birth Tissue Products for Non-opioid Treatment of Post-surgical Pain
用于非阿片类药物治疗术后疼痛的出生纸巾产品
基本信息
- 批准号:10442516
- 负责人:
- 金额:$ 64.49万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAdverse effectsAfferent NeuronsAnti-Inflammatory AgentsAntiinflammatory EffectAttenuatedBirthBullous KeratopathyCaliberCellsCessation of lifeCicatrixClinicalComplexCorneaCytoskeletonDevelopmentEye diseasesFlow CytometryGoalsHumanHyaluronic AcidImmuneImmune TargetingInflammationInflammatoryInjectionsInjuryInterleukin-10Ion ChannelLawsLeadMediatingMembraneMusMuscleNeuronsNociceptionOpioidOpioid AnalgesicsOverdosePTX3 proteinPainPain managementParticulatePatientsPersistent painPharmaceutical PreparationsPharmacotherapyPhenotypePhysiciansPostoperative PainPrincipal InvestigatorRadiationRattusResearch PersonnelRiskRodent ModelSafetySkinSpinal GangliaSurgical incisionsTRPV1 geneTestingTherapeutic EffectThickTissuesUmbilical cord structureUniversitiesallodyniabasecytokinedrug actionhealingin vivoindium arsenidemacrophagemast cellmedical schoolsmouse modelnon-opioid analgesicnoveloverdose deathpain inhibitionpain reductionpain reliefpre-clinicalprogramspublic health emergencyreceptorrecruitregenerativeresponseside effectskin woundvoltagewoundwound environmentwound healing
项目摘要
PROJECT SUMMARY
Post-surgical pain causes significant suffering to patients and an over-reliance on opioids for pain reduction.
However, opioid analgesics cause severe side effects and a risk of accidental death from overdose.
Unfortunately, effective non-opioid pain therapy remains lacking. We aim to determine if human cell and
tissue product (HCT/P), such as amniotic membrane and umbilical cord, can be developed for use as a novel
and safe treatment of post-surgical pain. In Aim 1, we will first prove the concept by demonstrating the
efficacy, receptor mechanisms, and safety of HCT/P for inhibiting post-surgical pain in murine models. Our
preliminary studies showed that intraoperative treatment with HCT/P reduced the development of
post-surgical pain in rats. In Aim 2, we will demonstrate that HCT/P targets immune cells as an indirect mode
of anti-pain action. We hypothesize that HCT/P promotes regenerative wound healing by suppressing
immune cell recruitment and inducing anti-inflammatory effects. Our recent studies suggested that the heavy
chain-hyaluronic acid-pentraxin 3 complex (HC-HA/PTX3) is a biologically active component uniquely
present in HCT/P. We will further explore how HC-HA/PTX3 polarizes macrophages differentiated from
human THP-1 cells to an M2 phenotype and whether HC-HA/PTX3 inhibits the activation of human LAD2
mast cell and release of pro-inflammatory cytokines. In Aim 3, we will examine the targeting of primary
sensory neurons as the direct mode of anti-pain action by HCT/P and HC-HA/PTX3. We will test whether
HC-HA/PTX3 reduces intrinsic membrane excitability and inhibits membrane ion channels in dorsal root
ganglion neurons. Furthermore, we will investigate whether the neuronal inhibition by HC-HA/PTX3 involves
a novel mechanism that depends on CD44-mediated cytoskeletal rearrangement. To achieve these goals,
we will combine the expertise of preclinical and translational pain researchers from Johns Hopkins University
School of Medicine and the GMP manufacturing of HCT/P at TissueTech, Inc. This study will provide
important rationales for developing HCT/P-based bioceuticals as a viable non-opioid treatment of
post-surgical pain. Such drugs will act not only directly, by dampening neuronal excitation, but also indirectly,
by changing the wound environment and orchestrating regenerative healing. Through the complementary
dual mode of action, we envision that birth HCT/P may lead to an optimal therapeutic effect with lasting pain
relief and a potential “cure” of post-surgical pain.
项目摘要
术后疼痛给患者带来了巨大的痛苦,并且过度依赖阿片类药物来减轻疼痛。
然而,阿片类镇痛药会引起严重的副作用,并有因过量而意外死亡的风险。
不幸的是,仍然缺乏有效的非阿片类药物疼痛治疗。我们的目标是确定人类细胞和
组织产品(HCT/P),如羊膜和脐带,可被开发用作新的
以及术后疼痛的安全治疗。在目标1中,我们将首先通过演示
HCT/P在小鼠模型中抑制术后疼痛的疗效、受体机制和安全性。我们
初步研究表明,术中HCT/P治疗可减少
大鼠术后疼痛。在目标2中,我们将证明HCT/P作为间接模式靶向免疫细胞
抗疼痛的作用。我们假设HCT/P通过抑制
免疫细胞募集和诱导抗炎作用。我们最近的研究表明,
链-透明质酸-正五聚蛋白3复合物(HC-HA/PTX 3)是一种独特的生物活性成分,
我们将进一步探索HC-HA/PTX 3如何极化巨噬细胞分化为HCT/P。
人THP-1细胞转化为M2表型以及HC-HA/PTX 3是否抑制人LAD 2的活化
肥大细胞和促炎细胞因子的释放。在目标3中,我们将研究主要目标
感觉神经元作为HCT/P和HC-HA/PTX 3抗疼痛作用的直接模式。我们将测试
HC-HA/PTX 3降低背根细胞膜兴奋性并抑制膜离子通道
神经节神经元此外,我们将研究HC-HA/PTX 3的神经元抑制是否涉及
依赖于CD 44介导的细胞骨架重排的新机制。为了实现这些目标,
我们将联合收割机结合来自约翰霍普金斯大学的临床前和转化疼痛研究人员的专业知识
TissueTech,Inc.医学院和HCT/P GMP生产本研究将提供
开发基于HCT/P的生物制品作为一种可行的非阿片类药物治疗的重要依据
术后疼痛这些药物不仅通过抑制神经元兴奋直接起作用,而且还间接起作用,
通过改变伤口环境和协调再生愈合。通过互补
双重作用模式,我们设想,出生HCT/P可能导致持久疼痛的最佳治疗效果
缓解和潜在的“治愈”术后疼痛。
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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{{ truncateString('Yun Guan', 18)}}的其他基金
Validation of a new large-pore channel as a novel target for neuropathic pain
验证新的大孔通道作为神经性疼痛的新靶点
- 批准号:
10774593 - 财政年份:2023
- 资助金额:
$ 64.49万 - 项目类别:
CRCNS: Computational Model of Chronic Pain Analgesia via Closed-Loop Peripheral Nerve Stimulation
CRCNS:通过闭环周围神经刺激进行慢性疼痛镇痛的计算模型
- 批准号:
10657620 - 财政年份:2021
- 资助金额:
$ 64.49万 - 项目类别:
CRCNS: Computational Model of Chronic Pain Analgesia via Closed-Loop Peripheral Nerve Stimulation
CRCNS:通过闭环周围神经刺激进行慢性疼痛镇痛的计算模型
- 批准号:
10395722 - 财政年份:2021
- 资助金额:
$ 64.49万 - 项目类别:
CRCNS: Computational Model of Chronic Pain Analgesia via Closed-Loop Peripheral Nerve Stimulation
CRCNS:通过闭环周围神经刺激进行慢性疼痛镇痛的计算模型
- 批准号:
10437031 - 财政年份:2021
- 资助金额:
$ 64.49万 - 项目类别:
Birth Tissue Products for Non-opioid Treatment of Post-surgical Pain
用于非阿片类药物治疗术后疼痛的出生纸巾产品
- 批准号:
10653711 - 财政年份:2020
- 资助金额:
$ 64.49万 - 项目类别:
Birth Tissue Products for Non-opioid Treatment of Post-surgical Pain
用于非阿片类药物治疗术后疼痛的出生纸巾产品
- 批准号:
10026707 - 财政年份:2020
- 资助金额:
$ 64.49万 - 项目类别:
Birth Tissue Products for Non-opioid Treatment of Post-surgical Pain
用于非阿片类药物治疗术后疼痛的出生纸巾产品
- 批准号:
10200173 - 财政年份:2020
- 资助金额:
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Mechanistic Study of Pain Inhibition by Activation of Non-nociceptive Afferent Fibers
非伤害性传入纤维激活抑制疼痛的机制研究
- 批准号:
10112977 - 财政年份:2019
- 资助金额:
$ 64.49万 - 项目类别:
Developing Novel Direct Current Stimulation Technology for Safe Precision Pain Treatment
开发新型直流电刺激技术以实现安全精准疼痛治疗
- 批准号:
9227078 - 财政年份:2016
- 资助金额:
$ 64.49万 - 项目类别:
MrgprC, A New Target for the Treatment of Neuropathic Pain
MrgprC,治疗神经性疼痛的新靶点
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8233966 - 财政年份:2011
- 资助金额:
$ 64.49万 - 项目类别:
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