ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Multiple targets of μ-opioid receptor-mediated presynaptic inhibition at primary afferent Aδ- and C-fibers.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 155 citations in OpenAlex.
- Noninvasive Diagnostic Ultrasound-Guided Focused Ultrasound Enables Selective, Reversible Inhibition of Peripheral Nociceptive Fibers and Prevents Acute Pain.bioRxiv : the preprint server for biology · 2026Article
- Modeling insights into potential mechanisms of opioid-induced respiratory depression within medullary and pontine networks.Journal of neurophysiology · 2026Article
- Repetitive neonatal pain increases spinal cord DNA methylation of the µ-opioid receptor.Pediatric research · 2025Article
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Prospective Evaluation of the Effectiveness of Brachial Plexus Nerve Block During the Perioperative Period in Long-Term Opioid Users Undergoing Upper Extremity Surgery - A Case Series.Local and regional anesthesia · 2025Article
- Large-scale investigation confirms TRPM3 ion channel dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.Frontiers in medicine · 2025Article
- Low-Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients.Frontiers in molecular biosciences · 2025Article
- μ-Opioid Receptor Modulation of the Glutamatergic/GABAergic Midbrain Inputs to the Mouse Dorsal Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Enkephalins and Pain Modulation: Mechanisms of Action and Therapeutic Perspectives.Biomolecules · 2024Review
- Tiam1-mediated maladaptive plasticity underlying morphine tolerance and hyperalgesia.Brain : a journal of neurology · 2024Article
- Interleukin-1α links peripheral CaScientific reports · 2024Article
- Interleukin-1α links peripheral CabioRxiv : the preprint server for biology · 2024Article
- Optogenetic and Chemogenic Control of Pain Signaling: Molecular Markers.International journal of molecular sciences · 2023Review
- Opioid suppression of an excitatory pontomedullary respiratory circuit by convergent mechanisms.eLife · 2023Article
- The Pain Management of Trauma Patients in the Emergency Department.Journal of clinical medicine · 2023Review
- Key differences in regulation of opioid receptors localized to presynaptic terminals compared to somas: Relevance for novel therapeutics.Neuropharmacology · 2023Review
- Dysregulation of Vesicular Glutamate Transporter VGluT2Frontiers in pharmacology · 2022Article
- The role of endogenous opioid neuropeptides in neurostimulation-driven analgesia.Frontiers in systems neuroscience · 2022Review
- Morphological investigations of endomorphin-2 and spinoparabrachial projection neurons in the spinal dorsal horn of the rat.Frontiers in neuroanatomy · 2022Article
- Chemokine CCL2 prevents opioid-induced inhibition of nociceptive synaptic transmission in spinal cord dorsal horn.Journal of neuroinflammation · 2021Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Agonists at μ-opioid receptors (MORs) represent the gold standard for the treatment of severe pain. A key element of opioid analgesia is the depression of nociceptive information at the first synaptic relay in spinal pain pathways. The underlying mechanisms are, however, largely unknown. In spinal cord slices with dorsal roots attached prepared from young rats, we determined the inhibitory effect of the selective MOR agonist [d-Ala(2), N-Me-Phe(4), Gly(5)-ol]-enkephalin (DAMGO) on monosynaptic Aδ- and C-fiber-evoked EPSCs in lamina I neurons. DAMGO depressed presynaptically Aδ- and C-fiber-mediated responses, indicating that MORs are expressed on central terminals of both fiber types. We next addressed the mechanisms of presynaptic inhibition. The effect of DAMGO at both Aδ- and C-fiber terminals was mainly mediated by an inhibition of N-type voltage-dependent Ca(2+) channels (VDCCs), and to a lesser extent of P/Q-type VDCCs. Inhibition by DAMGO was not reduced by K(+) channel blockers. The rate of miniature EPSCs was reduced by DAMGO in a dose-dependent manner. The opioid also reduced Ca(2+)-dependent, ionomycin-induced EPSCs downstream of VDCCs. DAMGO had no effect on the kinetics of vesicle exocytosis in C-fiber terminals, but decreased the rate of unloading of Aδ-fiber boutons moderately, as revealed by two-photon imaging of styryl dye destaining. Together, these results suggest that binding of opioids to MORs reduces nociceptive signal transmission at central Aδ- and C-fiber synapses mainly by inhibition of presynaptic N-type VDCCs. P/Q-type VDCCs and the transmitter release machinery are targets of opioid action as well.
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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.