Shan Zhi, Zhang Xuyang, Li Shengyun, Yu Tianming, Mamuti Maiwulanjiang, Zhao Fengdong
1Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
J Bone Joint Surg Am. 2017 Mar 15;99(6):472-481. doi: 10.2106/JBJS.16.00146.
Modic changes (inflammatory-like changes visible on magnetic resonance imaging [MRI] scans of a vertebral end plate) are common and are associated with low back pain, but their origin is unclear. To our knowledge, there have been no previous in vivo animal models of Modic changes. We hypothesized that Modic changes may be related to Propionibacterium acnes.
Ten New Zealand White rabbits were injected percutaneously with 1 mL of P. acnes (1.6 × 10 colony forming units/mL) into the subchondral bone superior to the L4-L5 and L5-L6 discs; 10 other control rabbits received sham injections at L4-L5 and 1 mL of normal saline solution (vehicle) at L5-L6. The subchondral bone superior to L3-L4 discs was untreated (blank). Development of Modic changes was investigated with MRI studies before the operation and at 2 weeks and 1, 2, 3, and 6 months postoperatively. Following sacrifice of the rabbits, histological analysis and microcomputed tomography (micro-CT) were performed, and blood samples were analyzed. Cytokine expression in end-plate tissues was quantified using real-time polymerase chain reaction (PCR).
The group that received P. acnes showed significantly increased T1-weighted signal intensity at 6 months (mean and standard deviation, 3.43 ± 0.41 [range, 2.42 to 4.44] compared with 2.43 ± 0.66 [range, 1.98 to 2.87] before the injection) and higher T2-weighted signal intensity at 6 months. Positive culture results were obtained from 9 of 20 samples injected with P. acnes. Specimens with positive cultures had a higher prevalence of Modic changes (4 of 9 samples positive for P. acnes compared with 3 of 11 samples negative for P. acnes). Real-time PCR showed significantly increased expression of tumor necrosis factor-α, interleukin-1β, and interferon-γ following injection of P. acnes, but no changes were seen on histological analysis, micro-CT, or blood analysis.
P. acnes can survive within the end-plate region and can initiate mild inflammatory-like responses from host cells, leading to signal intensity changes in MRI scans, which potentially resemble Modic changes.
Disc degeneration and low back pain are associated with Modic changes. Our results indicate that Modic changes can be associated with P. acnes in the conjunction area of the disc and subchondral bone. These results may be useful for understanding the underlying mechanisms of Modic changes and related pain.
Modic改变(在椎体终板的磁共振成像[MRI]扫描中可见的炎症样改变)很常见,且与腰痛相关,但其起源尚不清楚。据我们所知,此前尚无Modic改变的体内动物模型。我们推测Modic改变可能与痤疮丙酸杆菌有关。
将10只新西兰白兔经皮向L4-L5和L5-L6椎间盘上方的软骨下骨注射1 mL痤疮丙酸杆菌(1.6×10菌落形成单位/mL);另外10只对照兔在L4-L5处接受假注射,在L5-L6处注射1 mL生理盐水(溶媒)。L3-L4椎间盘上方的软骨下骨未处理(空白)。在手术前以及术后2周、1、2、3和6个月通过MRI研究调查Modic改变的发生情况。在处死兔子后,进行组织学分析和微型计算机断层扫描(micro-CT),并分析血样。使用实时聚合酶链反应(PCR)对终板组织中的细胞因子表达进行定量。
接受痤疮丙酸杆菌注射的组在6个月时T1加权信号强度显著增加(平均值和标准差,3.43±0.41[范围,2.42至4.44],而注射前为2.43±0.66[范围,1.98至2.87]),且在6个月时T2加权信号强度更高。在注射痤疮丙酸杆菌的20个样本中,有9个培养结果为阳性。培养结果为阳性的标本中Modic改变的发生率更高(痤疮丙酸杆菌阳性的9个样本中有4个,痤疮丙酸杆菌阴性的11个样本中有3个)。实时PCR显示注射痤疮丙酸杆菌后肿瘤坏死因子-α、白细胞介素-1β和干扰素-γ的表达显著增加,但在组织学分析、micro-CT或血液分析中未见变化。
痤疮丙酸杆菌可在终板区域内存活,并可引发宿主细胞的轻度炎症样反应,导致MRI扫描中的信号强度改变,这可能类似于Modic改变。
椎间盘退变和腰痛与Modic改变相关。我们的结果表明,Modic改变可能与椎间盘和软骨下骨结合区域的痤疮丙酸杆菌有关。这些结果可能有助于理解Modic改变及相关疼痛的潜在机制。