The Bacterial Basis of Degenerative Disc Disease: Propionibacterium Acnes, Inflammation, and the Immune Response

退行性椎间盘疾病的细菌基础：痤疮丙酸杆菌、炎症和免疫反应

• 批准号: 9765162
• 负责人: Deborah Gorth
• 金额: $ 4.69万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2020-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765162
• 关键词: Acne; Address; Affect; American; Antibiotic Therapy; Antibiotics; Antigen Presentation; Antigen-Presenting Cells; Back Pain; Bacterial Infections; Behavior; Binding; Cell physiology; Cells; Characteristics; Chronic low back pain; Clinical; Clinical Research; Coculture Techniques; Computer Simulation; Data; Disease; Economic Burden; Evaluation; Event; Exposure to; Expression Profiling; Future; Gene Expression; Goals; Grooming; Health; Human Pathology; Immune; Immune response; Immune system; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Intervertebral disc structure; Lead; Link; Literature; Low Back Pain; Mediating; Molecular; Morphology; Neck Pain; Needles; Opportunistic Infections; Pain; Pain intensity; Pathogenesis; Pathology; Pathway interactions; Patients; Phenotype; Plant Roots; Play; Production; Propionibacterium acnes; Puncture procedure; Rattus; Research; Role; Sampling; Slipped Disk; Societies; T-Lymphocyte; Testing; Tissues; Treatment Efficacy; Tumor-infiltrating immune cells; Vertebral column; Work; antimicrobial; base; bone; clinical effect; clinically relevant; cytokine; design; disability; experimental study; global health; in vivo; intervertebral disk degeneration; macrophage; novel; novel strategies; nucleus pulposus; pain behavior; pain reduction; patient subsets; polarized cell; protein expression; response; sham surgery; success; therapeutic target

PROJECT SUMMARY Lower back and neck pain is a profoundly debilitating and prevalent condition. It is currently the worldwide leading cause of disability and is a major cause of lost work-days in Western society. The economic burden of this condition is conservatively estimated at $100-200 billion each year. Low back pain and intervertebral disc (IVD) health are inexorably linked. While the cellular events leading to painful degenerate IVDs are well characterized, the initiating events as well as the molecular relationship between disc degeneration and pain are not understood. Recent clinical studies implicate subclinical bacterial infection in the genesis of LBP; not only were multiple strains of Proprionibacterium acnes (P. acnes) isolated from painful herniated IVDs, but long term antibiotic treatment lead to a significant reduction of both disease-specific disability and back pain intensity. Despite the drawback of long-term antibiotic use, the striking success of treating LBP with antibiotics cannot be overlooked. Currently, there is no active research examining the molecular relationship between P. acnes and the pathogenesis of disc disease. From this perspective, understanding how P. acnes influences inflammation and immune cell function is likely to provide a new approach to understanding the relationship between the degenerative response and pain, thus creating a dramatic and transformative shift in treatment options for patients suffering from this pervasive, and often crippling condition.

项目总结 下背部和颈部疼痛是一种非常虚弱和普遍的疾病。它目前是全球范围内 这是导致残疾的主要原因，也是西方社会失去工作日的主要原因。中国的经济负担 保守估计，这种情况每年有1,000-2,000亿美元。腰背痛和腰间盘 (IVD)健康是密不可分的。虽然导致痛苦的退行性静脉畸形的细胞事件是好的 表征、启动事件以及椎间盘退变与疼痛的分子关系 是不被理解的。最近的临床研究表明，亚临床细菌感染与LBP的发生有关；而不是 只有从疼痛的腹股沟静脉畸形中分离出多种痤疮原杆菌(P.acnes)，但 长期使用抗生素治疗可显著减少因疾病而致残和背部疼痛 强度。尽管长期使用抗生素的缺点，但用抗生素治疗LBP的惊人成功 不容忽视。目前，还没有积极的研究来检验P. 痤疮与腰椎间盘疾病的发病机制。从这个角度来看，了解痤疮杆菌是如何影响 炎症和免疫细胞功能可能为理解这种关系提供了一种新的途径 退行性反应和疼痛之间的关系，从而在治疗中创造了戏剧性和变革性的转变 为患有这种无处不在的、往往是严重的疾病的患者提供选择。