Regulation of pain signaling by the innate immune system
Bibliographic record
Abstract
The innate immune system is the body's first response to infections and its activation gives rise to pain. How the innate immune system interacts with the sensory nervous system and contributes to pain is poorly understood. We have shown previously that intraplantar CFA injection leads to an upregulation of the deubiquitinase USP5 in dorsal root ganglia and spinal cord, and this in turn leads to an increase in the numbers of Cav3.2 T-type calcium channels in an activity dependent manner. Blocking USP5 interactions with cell permeant disruptor peptides mediates analgesia. Here we demonstrate that specific Toll-like receptors (TLRs) are up-regulated in response to CFA injection. This leads to macrophage infiltration into the dorsal root ganglia, and the production of interleukin 33 (IL33) which acts on sensory neuron to increase their activity. Block of spinal IL33/ST2 receptor signals attenuates CFA-induced inflammatory pain. The CFA induced upregulation of USP5 is abolished in TLR2 null mice, altogether indicating that the CFA mediated dysregulation of T-type calcium channel activity involves the activation of a TLR2-IL33-ST2 pathway, leading to the development of inflammatory pain.
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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 | 0.002 | 0.002 |
| 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".