Mu-opioid receptor knockout prevents changes in delta-opioid receptor trafficking induced by chronic inflammatory pain
Bibliographic record
Abstract
Previous studies from our laboratory have demonstrated that both chronic inflammatory pain, induced by intraplantar injection of complete Freund's adjuvant (CFA), and prolonged (48 h) stimulation of mu-opioid receptors (muOR) by systemic administration of a variety of selective agonists, resulted in enhanced plasma membrane targeting of delta-opioid receptors (deltaOR) in neurons of the dorsal spinal cord. To determine whether deltaOR trafficking induced by chronic inflammation was dependent on the activation of muOR, we investigated by immunogold cytochemistry the effects of intraplantar CFA injection on the plasma membrane density of deltaOR in muOR knockout (KO) mice. In untreated wild-type (WT) mice, only a small proportion of deltaOR was associated with neuronal plasma membranes in the dorsal horn of the spinal cord. The CFA-induced inflammation produced a significantly higher ratio of plasma membrane to intracellular receptors, as well as a 75% increase in the membrane density of immunoreactive deltaOR, in dendrites of the ipsilateral dorsal horn as compared to untreated mice. This increase in the membrane density of deltaOR was likely due to a recruitment of receptors from intracellular stores since no difference in the overall deltaOR immunolabeling density was evident between CFA-treated and untreated mice. Most importantly, the CFA-induced changes in deltaOR plasma membrane insertion seen in WT animals were not present in the spinal cord of muOR KO mice. These results demonstrate that the integrity of muOR is necessary for CFA-induced changes in deltaOR trafficking to occur and suggest that these changes could be elicited by stimulation of muOR by endogenous opioids released in response to chronic 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 | 0.001 |
| 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 | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".