Characterization of the Effect of Chronic Opioid Use on Immune Cell Mediated Endogenous Opioid Analgesia
Bibliographic record
Abstract
Rationale: Cells of the innate (neutrophils, macrophages, microglia) and adaptive (CD4 and CD8 T-cells) immune systems have been recognized for their role in the resolution of pain after tissue injury in addition to that related to wound healing. Immune cells containing the endogenous opioid peptides enkephalin, endorphin, and dynorphin accumulate around inflamed tissue. Activation of local neuronal opioid receptors by these endogenous opioids results in decreased post-injury pain. The contribution of immune-mediated endogenous opioid analgesia to overall pain control after surgery, in the context of multimodal analgesia, has not been well characterized. Prolonged exposure to exogenous opioids can have significant effects on immunological surveillance and response to injury and infection. Evidence regarding the effect of long-term exogenous opioid exposure on the immune-mediated endogenous opioid system is inconsistent and the level of evidence to support a conclusion is weak. Hypothesis: Chronic exposure to opioids alters the immune-mediated opioid response to surgical tissue injury with reduced levels of endogenous opioids being produced by macrophages and T-cells. Objective: Characterize endogenous opioid levels in macrophages and T-cells from opioid exposed and opioid unexposed patients undergoing surgery. Outcomes: Levels of endogenous opioid transcripts the opioid precursors - proopiomelanocortin (POMC), proenkephalin (PENK) and prodynorphin (PDYN) in the immune cell populations of opioid naïve and opioid experienced surgery patients. Design: A prospective cohort study design will be used for adults 18 years and older, presenting for elective surgery. Blood samples will be obtained intraoperatively from male opioid naive (n=10) and male opioid experienced patients (n=10). Peripheral blood mononuclear cells (PBMCs) will be isolated, and qPCR will be used to measure the levels of endogenous opioid transcripts (PENK, POMC, PDYN) in the different immune cell populations. Setting: University of Alberta Hospital Participants: Adults undergoing elective surgery at the University of Alberta Hospital
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.006 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.008 | 0.002 |
| Research integrity | 0.001 | 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 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".