Long‐term histological analysis of innervation and macrophage infiltration in a mouse model of intervertebral disc injury–induced low back pain
Bibliographic record
Abstract
Low back pain (LBP) is a leading cause of global disability. Multiple anatomical, cellular, and molecular factors are implicated in LBP, including the degeneration of lumbar intervertebral discs (IVDs). We previously described a mouse model that displays behavioral symptoms of chronic LBP. Here, we investigated the development of pathological innervation and macrophage infiltration into injured IVDs following a puncture injury in mice over 12 months. 2-month old CD1 female mice underwent a single puncture of the ventral L4/5 IVD using a 30G needle, and were sacrificed 4 days and 0.5-, 3-, 6- and 12-months post-injury. Severity of disc degeneration was assessed using colorimetric staining. IVD innervation was measured by PGP9.5-immunoreactivity (-ir) and calcitonin gene-related peptide-ir (CGRP-ir). Macrophage accumulation into IVDs was detected by F4/80-ir. Mechanical IVD injury resulted in severe degeneration and increased PGP9.5-ir nerve fiber density starting at 4 days that persisted for up to 12 months and dorsal herniations began to occur at 3 months. CGRP-ir was also upregulated in injured IVDs, with the largest increase at 12 months after injury. Infiltration of F4/80-ir macrophages was observed in injured IVDs by day 4 both dorsally and ventrally, with the latter diminishing in the later stage. Persistent LBP is a complex disease with multiple underlying pathologies. By highlighting pathological changes in IVD innervation and inflammation, our study suggests that strategies targeting these mechanisms might be useful therapeutically.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.006 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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; a candidate call from one teacher head, not a consensus.
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".