Spinal astrogliosis in an animal model of cancer-induced bone pain
Bibliographic record
Abstract
1000 Pain associated with malignancy in bone is a significant source of morbidity in breast and prostate cancer metastases. Understanding the unique pathophysiological mechanisms leading to bone pain is essential to the development of effective therapies. It is accepted that astroglial activation plays a role in the development of chronic bone pain, although it is unclear whether this is causative to the structural encoding of nociceptive signals and whether opiate analgesics influence the process. We examined spinal astrogliosis in a mouse model of cancer-induced bone pain with opiate analgesia and monitored disease progression with non-invasive optical imaging techniques. This was confirmed by histology. Rat prostate cancer cells (MATLyLu) expressing a green fluorescent protein (GFP) tag were injected into the right femur of 11 Balb/c nude mice (plus 5 mice as non-injected controls). Three injected and one control animal received twice daily doses of an opiate analgesic (buprenorphine, 0.05 mg/kg s.c.) throughout the experiment. Behavioral evidence for bone pain was referenced by measurement of mechanical allodynia with a Touch Test Sensory Evaluator (Stoelting, Wood Dale, IL). Tumor growth was assessed non-invasively with in vivo fluorescence imaging using a thermoelectrically cooled camera (Andor Ikon; excitation = 440-495 nm, emission = 505-580 nm). Skin temperatures were measured using an infrared camera (FLIR ThermaCam SC2000) to assess localized or systemic inflammatory responses. At the end of the experiment, x-rays (Faxitron Model MX-20) were used to determine the extent of osteolysis, then the spinal cord, kidneys, and both femurs were harvested for processing. The femurs were decalcified, paraffin embedded, and analyzed by both fluorescence microscopy and hematoxylin & eosin. Immunohistochemistry on the spinal cords employed a polyclonal rabbit anti-bovine antibody to Glial Fibrillary Acidic Protein (GFAP; Dako N1506) with kidney as a negative control. Results show little evidence to support an interaction of opiate analgesia with astroglial activation. However, the imaging data suggest a possible impact on tumor growth, although this may be model-specific. Interestingly, astrocyte activation occurred without x-ray or histological evidence for significant osteolysis, but this may also be unique to the cells used. Temperature and GFAP data corroborate that the induced pain is bone tumour specific and not likely due to a significant inflammatory component. Astrocyte activation without osteolysis suggests that tumor-specific factors may be involved in the process. (Supported by: Canadian Institutes of Health Research)
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.003 | 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; a candidate call from one source (direct Gemma or distilled Codex), 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".