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

项目摘要 下背部和颈部疼痛是一种严重的衰弱和普遍的条件。目前，全球 残疾的主要原因，是西方社会损失工作日的主要原因。的经济负担 保守估计每年约为1000亿至2000亿美元。下背痛与椎间盘 (IVD)健康是不可分割联系。虽然细胞事件导致痛苦的退化IVD是很好的 特征，起始事件以及椎间盘退变和疼痛之间的分子关系 不被理解。最近的临床研究表明，LBP的发生与亚临床细菌感染有关; 只有多株痤疮丙酸杆菌（P. acnes）从疼痛的突出IVD中分离出来， 长期抗生素治疗可显著减少疾病特异性残疾和背痛 强度。尽管长期使用抗生素有缺点，但用抗生素治疗下腰痛的惊人成功 不容忽视目前，还没有活跃的研究探讨P。 痤疮和椎间盘疾病的发病机制。从这个角度来看，了解痤疮丙酸杆菌如何影响 炎症和免疫细胞功能可能提供一种新的方法来理解这种关系 在退行性反应和疼痛之间，从而创造了一个戏剧性的和变革性的治疗转变， 为患有这种普遍的，往往是致残性疾病的患者提供了选择。

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.