BDNF Driven Coupling Between KCC2 Downregulation and Fyn-Dependent Phosphorylation of GluN2B NMDA Receptors in Human Spinal Pain Processing
Bibliographic record
Abstract
Hyperexcitation of neurons in the dorsal horn of the spinal cord leads to chronic pain.In rodent pain models, the neurotrophic factor BDNF mediates loss of inhibitory signalling.This permits enhancement of excitatory GluN2B-NMDAR currents in lamina I neuronal synapses.However, whether this pathway is conserved between rodents and humans as well as between sexes is unknown.We developed a human ex vivo BDNF model of pathological pain using postmortem human spinal tissue.We found that ex vivo BDNF downregulates KCC2 and active STEP61 and upregulates active Fyn and phosphorylated GluN2B at the superficial dorsal horn in both human and rodent males.We also show that BDNF increases intracellular KCC2 of superficial dorsal horn neurons.Thus, our human model may connect the vast translational divide between rodent and human chronic pain mechanisms to identify and validate new therapeutic targets for human chronic pain.
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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 | 0.000 | 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) | 0.004 | 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 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".