Editorial: Opioid-induced respiratory depression: neural circuits and cellular pathways
Bibliographic record
Abstract
Editorial on the Research Topic Opioid-induced respiratory depression: neural circuits and cellular pathwaysThe analgesic and euphoric properties of the opium poppy were discovered thousands of years ago, and opiates and their derivatives have been widely used for pain management ever since.While opiates have beneficial properties such as analgesia, they also present side effects such as tolerance, addiction, sedation, and respiratory depression, which can be lethal in overdose.This latter side effect is due to the action of opioid drugs on their cognate opioid receptors, which are expressed in key respiratory regions of the brainstem.Opioids were first used to dissect the mechanisms controlling the timing of the respiratory phase (Palkovic et al., 2020;Ramirez et al., 2021).Opioid receptors have been found in multiple respiratoryrelated areas of the brainstem (Ding et al., 1996).Opioids activate postsynaptic receptors to hyperpolarize neurons in the Kölliker-Fuse nucleus (Levitt et al., 2015), the preBötzinger complex (Montandon et al., 2011), and premotor neurons (Bateman and Levitt, 2023).Opioids also decrease glutamate release presynaptic to respiratory neurons in the preBötzinger complex (Wei and Ramirez, 2019;Bateman and Levitt, 2023) and to premotor neurons (Bateman and Levitt, 2023).Other studies have used localized opioid receptor knock-out preparations (Bachmutsky et al., 2020;Varga et al., 2020) or localized injections of the opioid antagonist naloxone (Palkovic et al., 2021;Palkovic et al., 2022) to determine which brainstem areas are affected by clinically relevant opioid concentrations.Researchers have found that global opioid-induced respiratory depression (OIRD) resulted from a combined effect on the parabrachial nucleus/Kölliker-Fuse complex, the preBötzinger complex, the caudal medullary raphe, and possibly other areas supplying respiratory drive, and that the contribution of the individual areas depended on the opioid concentration.More recently, the increasing number of fatal overdoses in patients with substance use disorders has spurred pragmatic clinical research to identify solutions to reverse and prevent OIRD.The animal studies included in this Research Topic focus on mechanisms of respiratory failure in different model organisms, such as rodents, goats, and dogs, and at different developmental stages, including prenatal, juvenile, and adult, bridging the gap between basic science and clinical research areas.These studies challenge the standard view that opioids uniformly reduce minute ventilation through a decrease in respiratory rate and
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.004 | 0.013 |
| Meta-epidemiology (narrow) | 0.004 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.002 |
| Bibliometrics | 0.003 | 0.001 |
| Science and technology studies | 0.003 | 0.002 |
| Scholarly communication | 0.005 | 0.003 |
| Open science | 0.003 | 0.001 |
| Research integrity | 0.010 | 0.013 |
| Insufficient payload (model declined to judge) | 0.027 | 0.019 |
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".