The Influence of Direct Inoculation of Propionibacterium acnes on Modic Changes in the Spine: Evidence from a Rabbit Model.

Abstract

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.