ArticleEMBO molecular medicine2013
The K(+) channel GIRK2 is both necessary and sufficient for peripheral opioid-mediated analgesia.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.
- Effect of Fentanyl as an Adjuvant to Brachial Plexus Block for Upper Extremity Surgeries: A Systematic Review and Meta-Analysis of RCTs.Pain research & management · 2022Pooled it
- Enkephalin-producing regulatory T cells in the skin restrain local inflammation through control of nociception.Science immunology · 2025Article
- Activation of G protein gated inwardly rectifying potassium (GIRK) channels in keratinocytes mediates peripheral kappa opioid receptor-mediated antinociception.Neuropharmacology · 2025Article
- Opioids-Induced Long QT Syndrome: A Challenge to Cardiac Health.Cardiovascular toxicology · 2024Review
- Novel Opioids in the Setting of Acute Postoperative Pain: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Regulatory lipid vicinal diols counteract the biological activity of epoxy fatty acids and can act as biomarkers and mechanisms for disease progression.Pharmacology & therapeutics · 2023Review
- Modulation of G-protein activation, calcium currents and opioid receptor phosphorylation by the pH-dependent antinociceptive agonist NFEPP.Frontiers in molecular neuroscience · 2023Article
- Peripheral ablation of type III adenylyl cyclase induces hyperalgesia and eliminates KOR-mediated analgesia in mice.JCI insight · 2022Article
- Sodium Channels and Local Anesthetics-Old Friends With New Perspectives.Frontiers in pharmacology · 2022Review
- Morphine coordinates SST and PV interneurons in the prelimbic cortex to disinhibit pyramidal neurons and enhance reward.Molecular psychiatry · 2021Article
- Peripherally Acting Opioids in Orofacial Pain.Frontiers in neuroscience · 2021Review
- A low pKa ligand inhibits cancer-associated pain in mice by activating peripheral mu-opioid receptors.Scientific reports · 2020Article
- Identification of Novel Targets of Knee Osteoarthritis Shared by Cartilage and Synovial Tissue.International journal of molecular sciences · 2020Article
- Voltage modulates the effect of μ-receptor activation in a ligand-dependent manner.British journal of pharmacology · 2020Article
- Antinociceptive effect of selective G protein-gated inwardly rectifying K+ channel agonist ML297 in the rat spinal cord.PloS one · 2020Article
- KFrontiers in cellular neuroscience · 2020Review
- G Protein-Gated Inwardly Rectifying Potassium Channel Subunit 3 is Upregulated in Rat DRGs and Spinal Cord After Peripheral Nerve Injury.Journal of pain research · 2020Article
- Candidate gene analyses for acute pain and morphine analgesia after pediatric day surgery: African American versus European Caucasian ancestry and dose prediction limits.The pharmacogenomics journal · 2019Article
- Differential Expression of Neuroinflammatory mRNAs in the Rat Sciatic Nerve Following Chronic Constriction Injury and Pain-Relieving Nanoemulsion NSAID Delivery to Infiltrating Macrophages.International journal of molecular sciences · 2019Article
- Noncanonical Ion Channel Behaviour in Pain.International journal of molecular sciences · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The use of opioid agonists acting outside the central nervous system (CNS) is a promising therapeutic strategy for pain control that avoids deleterious central side effects such as apnea and addiction. In human clinical trials and rat models of inflammatory pain, peripherally restricted opioids have repeatedly shown powerful analgesic effects; in some mouse models however, their actions remain unclear. Here, we investigated opioid receptor coupling to K(+) channels as a mechanism to explain such discrepancies. We found that GIRK channels, major effectors for opioid signalling in the CNS, are absent from mouse peripheral sensory neurons but present in human and rat. In vivo transgenic expression of GIRK channels in mouse nociceptors established peripheral opioid signalling and local analgesia. We further identified a regulatory element in the rat GIRK2 gene that accounts for differential expression in rodents. Thus, GIRK channels are indispensable for peripheral opioid analgesia, and their absence in mice has profound consequences for GPCR signalling in peripheral sensory neurons.
Indexed as
Identifiers
What OpenQuestion holds
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.