Modic Change-Like Lesion Presence and Extent Correlate With Pain-Like Behaviour in a Lumbar Endplate Injury Rat Model

Modic changes (MC) are vertebral magnetic resonance imaging (MRI) signal intensity changes commonly seen in chronic low back pain patients. Despite their prevalence, pain mechanisms remain unclear, limiting the development of disease-modifying treatments. Animal models are critical for investigating pain mechanisms, however few MC animal models exist, and they rarely address pain-like behaviors. The aim of this study was to develop an MC animal model and to correlate MRI features with pain-like behavior. Sixteen 4-5-month-old Sprague-Dawley rats were assigned to sham (n=4), endplate injury (EP)+TNF-α (n=6), or EP+ Cutibacterium acnes ( C.acnes ) (n=6) groups. Sham rats underwent anterior abdominal incision with L4-L6 lumbar spine exposure. EP injury was induced by puncturing the caudal L4 and cranial L6 endplates through the disc ( Figure 1A ), followed by an intradiscal TNF-α (2.5ng/2.5ul PBS) or C.acnes (1.8×10 5 CFUs) injection (mimicking MC subtypes 1 ). Pain-like behavior was assessed biweekly using the von Frey assay and analyzed with a two-way ANOVA. Ex-vivo T1w and T2w MRI was performed post-euthanasia. Transverse EP injury extent (0–3), disc degeneration (DD) (0–3), and both MC-like lesion presence (0,1), and extent (0–3) in L4-L6 endplates were evaluated. The preoperative normalized pain-like behavior at week seven was correlated with the sum of each feature. Animals in both EP injury groups showed a significantly lower hindpaw withdrawal threshold (indicating increased pain-like behavior) from week one to seven ( Figure 1B ). There was no significant difference in pain-like behavior between the injury groups at any of the time points evaluated. The presence ( Figure 1C,E ) and extent (not shown, r 2 =0.710, p<0.009) of MC-like lesions showed a strong correlation with pain-like behavior. The extent of EP injuries trended toward significant correlation with pain-like behavior ( Figure 1D ), while DD did not correlate with pain-like behavior at all (not shown, r 2 =0.120, p=0.402). We established a rat lumbar EP injury model that induces pain-like behavior and MC-like lesions on MRI, reflecting key aspects of the human MC pathobiology. Pain-like behavior correlated strongly with MC-like lesions but not the EP injury extent or DD, highlighting the role of bone marrow changes in pain. This is consistent with the high positive predictive value of MC lesions for discography concordant pain 2,3 . Notably, pain-like behavior did not differ between injury groups, reflecting findings in MC patients with different subtypes 4 . Our model provides a valuable tool for investigating painful MC mechanisms and highlights bone marrow as a key contributor to pain. For any figures or tables, please contact the authors directly.