ISSLS Prize Winner
Bibliographic record
Abstract
In Brief Study Design. Immunohistochemical and behavioral study using the SPARC (secreted protein, acidic, rich in cysteine)-null mouse model of low back pain (LBP) associated with accelerated intervertebral disc (IVD) degeneration. Objective. To determine if behavioral signs of LBP in SPARC-null mice are accompanied by sensory nervous system plasticity. Summary of Background Data. IVD pathology is a significant contributor to chronic LBP. In humans and rodents, decreased expression of SPARC is associated with IVD degeneration. We previously reported that SPARC-null mice exhibit age-dependent behavioral signs of chronic axial LBP and radiating leg pain. Methods. SPARC-null and age-matched control young, middle-aged, and old mice (1.5, 6, and 24 mo of age, respectively) were evaluated. Cutaneous hind paw sensitivity to cold, heat, and mechanical stimuli were evaluated as measures of radiating pain. The grip force and tail suspension assays were performed to evaluate axial LBP. Motor impairment was assessed using an accelerating rotarod. IVD innervation was identified by immunohistochemistry targeting the nerve fiber marker PGP9.5 and the sensory neuropeptide calcitonin gene-related peptide (CGRP). Sensory nervous system plasticity was evaluated by quantification of CGRP- and neuropeptide-Y-immunoreactivity (-ir) in dorsal root ganglia neurons and CGRP-ir, GFAP-ir (astrocyte marker), and Iba-1-ir (microglia marker) in the spinal cord. Results. SPARC-null mice developed hypersensitivity to cold, axial discomfort, age-dependent motor impairment, age-dependent increases in sensory innervation in and around the IVDs, age-dependent upregulation of CGRP and neuropeptide-Y in dorsal root ganglia, and age-dependent upregulation of CGRP, microglia, and astrocytes in the spinal cord dorsal horn. Conclusion. Increased innervation of degenerating IVDs by sensory nerve fibers and the neuroplasticity in sensory neurons and spinal cord could contribute to the underlying pathobiology of chronic discogenic LBP. Level of Evidence: N/A SPARC (secreted protein, acidic, rich in cysteine)-null mice show behavioral signs of axial low back pain, radiating leg pain and reduced physical function. Sensory innervation in or near the intervertebral discs, pain-related neuropeptide expression in dorsal root ganglia neurons, and astrocyte and microglia expression in the spinal cord were increased with age and in SPARC-null mice.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".