Regulation of SCI-induced pain by macrophages and exercise

巨噬细胞和运动对 SCI 引起的疼痛的调节

基本信息

批准号：
10736378
负责人：
MEGAN R DETLOFF
金额：
$ 44.26万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-18 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10736378
关键词：
Ablation Adjuvant Therapy American Analgesics Attenuated Cells Chronic Control Groups Cyclic AMP Data Development Dichloromethylene Diphosphonate Disease Encapsulated Enzyme-Linked Immunosorbent Assay Exercise Flow Cytometry Funding Harvest Healthcare Systems Human Hydrophobicity Impairment In Vitro Incidence Individual Infiltration Inflammation Inflammatory Injections Injury Institute of Medicine (U.S.)Liposomes Macrophage Macrophage Activation Maintenance Measures Modeling Molecular Nanodelivery Neuroimmune Neurons Nociceptors Pain Phenotype Physiological Population Prevention Probability Process Rattus Regulation Rehabilitation therapy Reporting Role Rolipram Sensory Serum Spinal Ganglia Spinal cord injury Subgroup System Technology Testing Therapeutic Walking axonal sprouting chronic neuropathic pain chronic pain cost cytokine disability exercise rehabilitation exosome extracellular vesicles improved in vivo inhibitor injured nanopolymer nanotherapeutic neuronal excitability neuropathology pain behavior pain reduction painful neuropathy phosphodiesterase IV prevent spinal cord injury pain transmission process

项目摘要

PROJECT SUMMARY Spinal cord injury (SCI) impairs sensory transmission and leads to chronic, debilitating neuropathic pain. Chronic pain afflicts over 100 million Americans and creates an enormous burden on US health care systems, costing over half a trillion dollars annually according to a recent report from the Institute of Medicine. While our understanding of the molecular basis underlying the development of chronic pain has improved, the available therapeutics provide limited relief. While our lab and others have shown that early post-SCI rehab can prevent pain development, early rehab in human SCI may not be possible due to the multisystem, polytraumatic injuries individuals with SCI sustain. Thus, there is a critical need for an adjuvant therapy to aid those individuals who are unable to participate in early rehab. Neuropathic pain is increasingly recognized as a neuroimmune disorder. While macrophages are regarded as key regulators of chronic pain development, it is unclear whether they are acting in an inflammatory or reparative manner. This R01 seeks to better understand how or if the activation state of macrophages influences nociceptive neuron excitability and pain development after SCI. We will utilize an established spinal cord injury model of neuropathic pain development and drive macrophage activation state by post-injury rehab, intrathecal administration of exosomes derived from Raw 264.7 macrophages stimulated in vitro or a phosphodiesterase 4 inhibitor by a polymer nanodelivery system that specifically targets macrophages. This proposal seeks to understand the role of macrophages that infiltrate the dorsal root ganglia and persist there chronically after SCI both in the development and maintenance of chronic neuropathic pain.

项目摘要脊髓损伤（SCI）会损害感觉传播，并导致慢性，使神经性衰弱疼痛。慢性疼痛困扰着超过1亿美国人，并为美国医疗保健带来了巨大的负担根据医学研究所的最新报告，系统每年耗资超过半万亿美元。尽管我们对慢性疼痛发展的分子基础的理解有所改善，但可用的治疗方法可提供有限的救济。 While our lab and others have shown that early post-SCI rehab 可以防止疼痛的发育，由于多系统，可能无法进行人类SCI的早期康复， SCI维持的个体多发性伤害。因此，急需辅助治疗以帮助那些无法参加早期康复的人。神经性疼痛越来越被认为是神经免疫性障碍。尽管巨噬细胞被认为是慢性疼痛发展的关键调节剂，但它是尚不清楚它们是以炎症或修复的方式起作用。这个R01试图更好地理解巨噬细胞的激活状态如何影响伤害性神经元的兴奋性和疼痛的发展科幻之后。我们将利用既定的神经性疼痛发展和动力的脊髓损伤模型巨噬细胞激活状态通过伤害后康复，鞘内给予原始的外泌体 264.7巨噬细胞在体外或通过聚合物纳米传递系统刺激体外或磷酸二酯酶4 这特别针对巨噬细胞。该提议旨在了解渗透的巨噬细胞的作用在Sci的发展和维护中，背侧根神经节在SCI之后长期存在于此慢性神经性疼痛。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Modelling at-level allodynia after mid-thoracic contusion in the rat.

DOI：
10.1002/ejp.1711
发表时间：
2021-04
期刊：
European journal of pain (London, England)
影响因子：
0
作者：
Blumenthal GH;Nandakumar B;Schnider AK;Detloff MR;Ricard J;Bethea JR;Moxon KA
通讯作者：
Moxon KA

Plasticity in Cervical Motor Circuits following Spinal Cord Injury and Rehabilitation.