Restoration of Cingulate Long-Term Depression by Enhancing Non-apoptotic Caspase 3 Alleviates Peripheral Pain Hypersensitivity
Bibliographic record
Abstract
Nerve injury in somatosensory pathways may lead to neuropathic pain, which affects the life quality of ∼8% of people. Long-term enhancement of excitatory synaptic transmission along somatosensory pathways contributes to neuropathic pain. Caspase 3 (Casp3) plays a non-apoptotic role in the hippocampus and regulates internalization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) subunits. Whether Casp3-AMPAR interaction is involved in the maintenance of peripheral hypersensitivity after nerve injury remained unknown. Here, we show that nerve injury suppresses long-term depression (LTD) and downregulates Casp3 in the anterior cingulate cortex (ACC). Interfering with interactions between Casp3 and AMPAR subunits or reducing Casp3 activity in the ACC suppresses LTD induction and causes peripheral hypersensitivity. Overexpression of Casp3 restores LTD and reduces peripheral hypersensitivity after nerve injury. We reveal how Casp3 is involved in the maintenance of peripheral hypersensitivity. Our findings suggest that restoration of LTD via Casp3 provides a therapeutic strategy for neuropathic pain management.
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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) | 0.000 | 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".