A289 DELTA OPIOID RECEPTOR ACTIVATION TRIGGERS BOTH ANTINOCICEPTIVE AND PRONOCICEPTIVE SIGNALING
Bibliographic record
Abstract
Opioid drugs are efficacious in the treatment of abdominal pain but increasing doses can activate pronociceptive signaling and paradoxically worsen pain. Although the mu opioid receptor (MOR) has been the classic analgesic target implicated in this signaling, there is growing evidence that delta opioid receptors (DOR) could also be important targets for analgesia. If so, however, they could also play a role in this paradoxical signaling. The present study examined whether exposure to low and high concentrations of the DOR agonist DADLE have opposite effects on the excitability of nociceptive DRG neurons. To examine the effects of high and low concentration DADLE, nociceptive mouse DRG neurons were dissociated from control mice and exposed to acute (30 min) or overnight incubation with 10 nM (low concentration) or 10 µM (high concentration) DADLE. Changes in neuronal excitability (decrease = antinociception, increase = pronociception) were recorded by measuring the rheobase (amount of current required to elicit an action potential) using patch clamp recordings. Patch clamp recordings of DRG neurons (small nociceptive neurons <25 pF) following acute incubation with DADLE exhibited opposing effects on excitability depending on the concentration. Acute incubation with low concentration DADLE inhibited the excitability of DRG neurons by 22.1% (p<0.05), whereas high concentration DADLE increased the excitability by 20.6% (p<0.05). Both effects were blocked by the DOR antagonist SDM25N (100 nM). Overnight incubation with low concentration DADLE had no effect on neuronal excitability, whereas the pronociceptive effect induced by high concentration persisted after overnight incubation (rheobase decreased 28.1% compared to control, p<0.001). Activation of DOR can have an important analgesic effect but high doses can also trigger paradoxical increases in pain signaling. The sustained effect of overnight exposure to high dose DADLE may reflect transcription and/or post transcriptional changes in the opioid signaling pathway. CCC
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".