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.

项目概要脊髓损伤 (SCI) 会损害感觉传递并导致慢性、衰弱性神经病疼痛。慢性疼痛困扰着超过一亿美国人，给美国医疗保健造成巨大负担根据医学研究所最近的一份报告，该系统每年花费超过 5000 亿美元。虽然我们对慢性疼痛发展的分子基础的了解有所提高，但现有的治疗方法只能提供有限的缓解。虽然我们的实验室和其他实验室已经表明，脊髓损伤后早期康复可以预防疼痛的发展，由于多系统，人类 SCI 的早期康复可能是不可能的，患有 SCI 的人会遭受多发性损伤。因此，迫切需要辅助治疗来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一种神经免疫紊乱。虽然巨噬细胞被认为是慢性疼痛发展的关键调节因子，但它尚不清楚它们是否以炎症或修复方式起作用。此 R01 旨在更好地理解巨噬细胞的激活状态如何或是否影响伤害感受神经元的兴奋性和疼痛的发展 SCI之后。我们将利用已建立的神经性疼痛发展和驱动的脊髓损伤模型通过损伤后康复、鞘内注射源自 Raw 的外泌体来激活巨噬细胞 264.7 通过聚合物纳米递送系统体外刺激巨噬细胞或磷酸二酯酶 4 抑制剂专门针对巨噬细胞。该提案旨在了解巨噬细胞渗透的作用背根神经节并在 SCI 后长期存在于该处，以发展和维持慢性神经性疼痛。

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）

Rolipram-loaded PgP nanoparticle reduces secondary injury and enhances motor function recovery in a rat moderate contusion SCI model.

负载咯利普兰的 PgP 纳米颗粒可减少大鼠中度挫伤 SCI 模型的继发性损伤并增强运动功能恢复。

DOI：
发表时间：
2023-09
期刊：
影响因子：
0
作者：
Gao, Jun;Khang, Min Kyung;Liao, Zhen;Webb, Ken;Detloff, Megan Ryan;Lee, Jeoung Soo
通讯作者：
Lee, Jeoung Soo

Therapeutic targets and nanomaterial-based therapies for mitigation of secondary injury after spinal cord injury.

用于减轻脊髓损伤后继发性损伤的治疗靶点和基于纳米材料的疗法。

DOI：
10.2217/nnm-2021-0113
发表时间：
2021-08-17
期刊：
Nanomedicine
影响因子：
5.5
作者：
Jun Gao;Minkyung Khang;Zhen Liao;M. Detloff;J. Lee
通讯作者：
J. Lee

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

大鼠中胸挫伤后水平异常性疼痛的建模。

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
Blumenthal, Gary H;Nandakumar, Bharadwaj;Schnider, Ashley K;Detloff, Megan R;Ricard, Jerome;Bethea, John R;Moxon, Karen A
通讯作者：
Moxon, Karen A

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

脊髓损伤和康复后颈椎运动回路的可塑性。