The role of BK channels in spinal microglia for the induction of neuropathic pain in mice
Bibliographic record
Abstract
The large-conductance Ca2+- and voltage-activated K+ (BK) channel is formed by four pore-forming subunits encoded by a single Slo1 gene and dually regulated by membrane voltage and intracellular Ca2+ levels. Recently, accumulating evidence using pharmacological methods suggests that the BK channel are associated with nociceptive sensitization. However, mechanisms underlying the effect of the BK channel on the regulation of pain signaling is still largely unknown. Here, we studied the role of the BK channel in the pain signaling in vivo using mice deficient for Slo1. In a partial sciatic nerve ligation (PSNL) model, Slo1 KO mice showed partially restored thermal hyperalgesia compared to their WT littermates. In microglia from WT mice, p38 MAPK phosphorylation was significantly increased after lysophosphatidic acid (LPA) treatment; conversely, it was not significantly upregulated in microglia from Slo1 KO mice, suggesting that the BK channel contributes to the signaling of microglial hyperactivation. Notably, intrathecal (i.t.) injection of microglia derived from WT mice into Slo1 KO mice before PSNL induced the normal development of hyperalgesia in Slo1 KO mice. These results indicate that the BK channel activation in spinal microglia, but not in neuron, contribute to the induction of neuropathic pain in this PSNL model.
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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 | 0.006 | 0.001 |
| 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".