Bone hypertrophy and reduced quality after nucleus pulposus aspiration induces low back pain-like behavior and neuronal hyperexcitability

초록

ObjectiveThere has been less explanation for whether lumbar disc injury, particularly through puncture and nucleus pulposus (NP) aspiration, can influence chronic low back pain (LBP). We aim to investigate whether intradiscal injury modifies spine structure and contributes to behavioral alteration and peripheral neuronal hyperexcitability in a rat model.MethodsMale Sprague-Dawley rats (n = 50) were subjected to lumbar disc (L4/5 and L5/6) puncture with nucleus pulposus aspiration (PUNCT) or sham surgery. Nociceptive processing was investigated through behavioral tests [dynamic weight bearing (DWB) and hindpaw withdrawal threshold], electrophysiological recordings of mechanosensitive single afferent nerves (MSAN), and calcium imaging of DiI-labeled dorsal root ganglion (DRG) neurons in response to capsaicin. Expression levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the disc and subchondral bone were quantified, and bone structure was assessed using ex vivo micro-computed tomography (mu CT).ResultsThe PUNCT group displayed significant behavioral changes, including increased forelimb dependency in DWB and decreased hindpaw withdrawal thresholds. Electrophysiological data indicated MSAN hyperexcitability with a reduced threshold to intradiscal pressure, and calcium imaging revealed heightened capsaicin (1 mu M)-induced calcium influx in DiI-labeled DRG neurons from the PUNCT group. NGF and BDNF expression significantly increased in both the disc and subchondral bone of the PUNCT group. mu CT analysis revealed hypertrophic bone volume, diminished trabecular bone quality, and localized bone erosion in the PUNCT group.ConclusionIntradiscal injury caused by puncture and NP aspiration induces spinal structural remodeling and peripheral neuronal sensitization, contributing to chronic LBP.

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