ArticleJournal of neurophysiology2012
Pain-facilitating medullary neurons contribute to opioid-induced respiratory depression.
Article in Journal of neurophysiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Invasive or noninvasive? A systematic review and network meta-analysis of acupuncture and acupressure to treat cancer pain.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Pooled it
- A projection atlas of excitatory and inhibitory inputs to the preBötzinger complex: substrates for multimodal breathing control.Journal of neurophysiology · 2026Article
- Acute buprenorphine exposure depresses neonatal respiratory chemoreflexes in the presence or absence of naloxone.bioRxiv : the preprint server for biology · 2026Article
- Endogenous opioids and the development of the mammalian respiratory control network.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Hypoxic effects of heroin and fentanyl and their basic physiological mechanisms.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- Interdependence of cellular and network properties in respiratory rhythmogenesis.bioRxiv : the preprint server for biology · 2023Article
- Article
- Parabrachial tachykinin1-expressing neurons involved in state-dependent breathing control.Nature communications · 2023Article
- Contribution of the caudal medullary raphe to opioid induced respiratory depression.Respiratory physiology & neurobiology · 2022Article
- Article
- Cannabinoids in the descending pain modulatory circuit: Role in inflammation.Pharmacology & therapeutics · 2020Review
- The Role of Peripheral Opioid Receptors in Triggering Heroin-induced Brain Hypoxia.Scientific reports · 2020Article
- Article
- Electrocortical changes associating sedation and respiratory depression by the opioid analgesic fentanyl.Scientific reports · 2019Article
- Compensatory Activation of Cannabinoid CB2 Receptor Inhibition of GABA Release in the Rostral Ventromedial Medulla in Inflammatory Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Entanglement between thermoregulation and nociception in the rat: the case of morphine.Journal of neurophysiology · 2016Article
- G-protein-gated Inwardly Rectifying Potassium Channels Modulate Respiratory Depression by Opioids.Anesthesiology · 2016Article
- μ opioid receptor activation hyperpolarizes respiratory-controlling Kölliker-Fuse neurons and suppresses post-inspiratory drive.The Journal of physiology · 2015Article
- Brainstem opioidergic system is involved in early response to experimental SAH.Translational stroke research · 2015Article
- Change in functional selectivity of morphine with the development of antinociceptive tolerance.British journal of pharmacology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
Abstract
Respiratory depression is a therapy-limiting side effect of opioid analgesics, yet our understanding of the brain circuits mediating this potentially lethal outcome remains incomplete. Here we studied the contribution of the rostral ventromedial medulla (RVM), a region long implicated in pain modulation and homeostatic regulation, to opioid-induced respiratory depression. Microinjection of the μ-opioid agonist DAMGO in the RVM of lightly anesthetized rats produced both analgesia and respiratory depression, showing that neurons in this region can modulate breathing. Blocking opioid action in the RVM by microinjecting the opioid antagonist naltrexone reversed the analgesic and respiratory effects of systemically administered morphine, showing that this region plays a role in both the analgesic and respiratory-depressant properties of systemically administered morphine. The distribution of neurons directly inhibited by RVM opioid microinjection was determined with a fluorescent opioid peptide, dermorphin-Alexa 594, and found to be concentrated in and around the RVM. The non-opioid analgesic improgan, like DAMGO, produced antinociception but, unlike DAMGO, stimulated breathing when microinjected into the RVM. Concurrent recording of RVM neurons during improgan microinjection showed that this agent activated RVM ON-cells, OFF-cells, and NEUTRAL-cells. Since opioids are known to activate OFF-cells but suppress ON-cell firing, the differential respiratory response to these two analgesic drugs is best explained by their opposing effects on the activity of RVM ON-cells. These findings show that pain relief can be separated pharmacologically from respiratory depression and identify RVM OFF-cells as important central targets for continued development of potent analgesics with fewer side effects.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.