ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Spinal G-protein-gated potassium channels contribute in a dose-dependent manner to the analgesic effect of mu- and delta- but not kappa-opioids.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 152 citations in OpenAlex.
- From nociception in aneural animals to human suffering: toward a comparative biology of pain.The Journal of experimental biology · 2025Review
- G protein-gated inwardly rectifying KHistology and histopathology · 2025Review
- Large-scale investigation confirms TRPM3 ion channel dysfunction in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.Frontiers in medicine · 2025Article
- 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
- Low-Dose naltrexone restored TRPM3 ion channel function in natural killer cells from long COVID patients.Frontiers in molecular biosciences · 2025Article
- Group III metabotropic glutamate receptors: guardians against excitotoxicity in ischemic brain injury, with implications for neonatal contexts.Pharmacological reports : PR · 2024Review
- Biasing GMolecular pharmacology · 2024Article
- Rapid emergence from dexmedetomidine sedation in Sprague Dawley rats by repurposing an αBMC anesthesiology · 2023Article
- Neuronal G protein-gated KAmerican journal of physiology. Cell physiology · 2022Review
- Review
- Antinociceptive effect and mechanism of supercritical carbon dioxide extract of Aloysia gratissima leaves in mice.Biomedical journal · 2021Article
- Opioid Receptor Regulation of Neuronal Voltage-Gated Calcium Channels.Cellular and molecular neurobiology · 2021Review
- Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination.eLife · 2020Article
- μ-Opioid receptors in primary sensory neurons are involved in supraspinal opioid analgesia.Brain research · 2020Article
- Opioid Receptors in Immune and Glial Cells-Implications for Pain Control.Frontiers in immunology · 2020Review
- Antinociceptive effect of selective G protein-gated inwardly rectifying K+ channel agonist ML297 in the rat spinal cord.PloS one · 2020Article
- GIRK Channel Activity in Dopamine Neurons of the Ventral Tegmental Area Bidirectionally Regulates Behavioral Sensitivity to Cocaine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Analgesic Effects of the GIRK Activator, VU0466551, Alone and in Combination with Morphine in Acute and Persistent Pain Models.ACS chemical neuroscience · 2019Article
- μ-Opioid receptors in primary sensory neurons are essential for opioid analgesic effect on acute and inflammatory pain and opioid-induced hyperalgesia.The Journal of physiology · 2019Article
- Regulators of G-Protein Signaling (RGS) Proteins Promote Receptor Coupling to G-Protein-Coupled Inwardly Rectifying Potassium (GIRK) Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Opioids can evoke analgesia by inhibiting neuronal targets in either the brain or spinal cord, and multiple presynaptic and postsynaptic inhibitory mechanisms have been implicated. The relative significance of presynaptic and postsynaptic inhibition to opioid analgesia is essentially unknown, as are the identities and relevant locations of effectors mediating opioid actions. Here, we examined the distribution of G-protein-gated potassium (GIRK) channels in the mouse spinal cord and measured their contribution to the analgesia evoked by spinal administration of opioid receptor-selective agonists. We found that the GIRK channel subunits GIRK1 and GIRK2 were concentrated in the outer layer of the substantia gelatinosa of the dorsal horn. GIRK1 and GIRK2 were found almost exclusively in postsynaptic membranes of putative excitatory synapses, and a significant degree of overlap with the mu-opioid receptor was observed. Although most GIRK subunit labeling was perisynaptic or extrasynaptic, GIRK2 was found occasionally within the synaptic specialization. Genetic ablation or pharmacologic inhibition of spinal GIRK channels selectively blunted the analgesic effect of high but not lower doses of the mu-opioid receptor-selective agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin. Dose-dependent contributions of GIRK channels to the analgesic effects of the -opioid receptor-selective agonists Tyr-D-Ala-Phe-Glu-Val-Val-Gly amide and [D-Pen(2,5)]-enkephalin were also observed. In contrast, the analgesic effect of the agonist (trans)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl] benzeneacetamide methanesulfonate hydrate was preserved despite the absence of GIRK channels. We conclude that the activation of postsynaptic GIRK1 and/or GIRK2-containing channels in the spinal cord dorsal horn represents a powerful, albeit relatively insensitive, means by which intrathecal mu- and -selective opioid agonists evoke analgesia.
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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.