Validating a novel rat modValidation of a Translational Model of Chronic Discogenic Low Back Painel of back pain

This project characterizes pain-related behaviors in a translational rat model designed to mimic acute-to-chronic discogenic low back pain. Using female Sprague–Dawley rats, the investigators compared outcomes after single-level (L5/6) versus multi-level (L4/5 and L5/6) lumbar intervertebral disc puncture (DP-1 and DP-2, respectively) against sham-operated controls over an 18-week period. The aim was to determine whether multi-level disc injury produces earlier onset, more persistent, and more widespread pain-related behaviors compared with single-level injury, and to relate behavioral changes to tissue degeneration and circulating biomarkers. Twenty-four adult female rats were allocated to DP-1, DP-2, or sham groups, and behavioral assays were conducted longitudinally to assess localized and remote mechanical sensitivity, tactile sensitivity, gait metrics, and social interaction. DP-2 rats developed local pressure sensitivity in the low back at 6 and 12 weeks, and remote pressure sensitivity in the upper thighs at 12 and 18 weeks. Tactile hypersensitivity of the hind paws emerged in DP-2 animals at 6, 12, and 18 weeks.

By contrast, DP-1 rats exhibited local and remote pressure sensitivity only at 12 weeks and did not display tactile hypersensitivity. Both DP-1 and DP-2 rats reduced distance traveled during gait testing relative to their pre-injury baselines across multiple timepoints; however, only DP-2 animals showed a statistically significant reduction in distance traveled relative to sham controls at 12 weeks. Social and behavioral assays revealed that DP-2 rats displayed fewer positive interactions with a novel adult female at 3 weeks, and exhibited hesitation and freezing during gait tests from 6 weeks onward, indicating behavioral features consistent with increased discomfort and altered affective responses. At study end (18 weeks), radiological and histological analyses confirmed reduced disc height and degeneration of the punctured intervertebral discs, linking behavioral hypersensitivity with structural disc changes.

Circulating biomarkers were also assessed: serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNFα) were elevated in DP-2 rats at 18 weeks relative to sham-operated animals, and levels of these markers correlated positively with measures of remote sensitivity in hind paws (tactile) and thighs (pressure). Collectively, the findings support the conclusion that multi-level disc injury in this rat model produces earlier onset, prolonged, and more extensive pain behaviors than single-level injury. The correspondence between behavioral outcomes, disc degeneration, and increased serum BDNF and TNFα suggests potential mechanistic roles for neurotrophic and inflammatory signaling in the transition from acute disc injury to chronic pain states. This validated model can serve as a translational platform for probing cellular and molecular mechanisms underlying discogenic low back pain and for preclinical testing of interventions aimed at preventing or reversing chronic pain trajectories following intervertebral disc injury.