Pathological Degeneration of Disc and Bone Is Associated With Chronic Low Back Pain in a Rat Model With Intradiscal Monosodium Iodoacetate.

Abstract

This study aimed to determine whether degeneration of intervertebral discs and subchondral bone correlates with the development of persistent low back pain (LBP) in a rat model with intradiscal monosodium iodoacetate (MIA), focusing on structural alterations, neuronal sensitization, and pain-related behavior. Male Sprague Dawley rats received MIA injections (2 mg in 2 μl) into L4/5 and L5/6 lumbar discs to induce degeneration. LBP-related behaviors were assessed over 42 days via dynamic weight-bearing and hindpaw withdrawal thresholds. Neuronal sensitization was evaluated via electrophysiological recordings of mechanosensitive afferent nerves (MSAN) and calcium imaging of labeled dorsal root ganglia (DRG) neurons innervating discs. Structural alterations in subchondral bone and disc were analyzed using in vivo/ex vivo µCT imaging, along with immunohistochemistry for TRPV1 and CGRP expression. Intradiscal MIA induced long-term LBP behaviors, characterized by forelimb weight-bearing shifts and reduced hindpaw withdrawal thresholds. MSAN exhibited hyperexcitability and lowered firing thresholds to intradiscal pressure, while DRG neurons showed enhanced TRPV1- and TRPA1-mediated calcium influx. µCT imaging revealed decreased disc volume and deteriorated trabecular bone quality. Histology confirmed disc and subchondral bone degeneration, with upregulated TRPV1 and CGRP expression in subchondral bone, indicating nociceptive fiber ingrowth. Linear discriminant analysis identified weight-bearing asymmetry (HindFore AUC), trabecular thickness, connectivity, and trabecular pattern factor as strong predictors of LBP development. Pathological degeneration of disc and bone is associated with chronic LBP through structural remodeling and peripheral neuronal sensitization. These findings suggest that therapeutic strategies targeting both tissues can alleviate chronic pain in degenerative spine conditions.