ArticlePloS one2013
Mu opioid receptors on primary afferent nav1.8 neurons contribute to opiate-induced analgesia: insight from conditional knockout mice.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 129 citations in OpenAlex.
- Chasing the Wrong Door for 30 Years: Is Suzetrigine the Key to Selective Pain Relief?Medicina (Kaunas, Lithuania) · 2026Review
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- An engineered nanobody inhibitor for molecular-to-circuit control of opioid receptor function.bioRxiv : the preprint server for biology · 2026Article
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- Circuit-selective pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception.Cell reports · 2025Article
- Complex opioid driven modulation of glutamatergic and cholinergic neurotransmission in a GABAergic brain nucleus associated with emotion, reward and addiction.bioRxiv : the preprint server for biology · 2025Article
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- The role of mu-opioid receptors in pancreatic islet α-cells.Journal of molecular endocrinology · 2025Article
- The μ-opioid receptor differentiates two distinct human nociceptive populations relevant to clinical pain.Cell reports. Medicine · 2024Article
- The role of mu-opioid receptors in pancreatic islet alpha cells.bioRxiv : the preprint server for biology · 2024Article
- Inputs to the locus coeruleus from the periaqueductal gray and rostroventral medulla shape opioid-mediated descending pain modulation.Science advances · 2024Article
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- TET1-Lipid Nanoparticle Encapsulating Morphine for Specific Targeting of Peripheral Nerve for Pain Alleviation.International journal of nanomedicine · 2024Article
- Cell-type specific molecular architecture for mu opioid receptor function in pain and addiction circuits.Neuropharmacology · 2023Review
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- Effect of Selective Lesions of Nucleus Accumbens µ-Opioid Receptor-Expressing Cells on Heroin Self-Administration in Male and Female Rats: A Study with NovelThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Modulation of G-protein activation, calcium currents and opioid receptor phosphorylation by the pH-dependent antinociceptive agonist NFEPP.Frontiers in molecular neuroscience · 2023Article
- Morphine pharmacokinetics and opioid transporter expression at the blood-retina barrier of male and female mice.Frontiers in pharmacology · 2023Article
- µ-Opioid Receptors Expressed by Intrinsically Photosensitive Retinal Ganglion Cells Contribute to Morphine-Induced Behavioral Sensitization.International journal of molecular sciences · 2022Article
- The mu opioid receptor and the orphan receptor GPR151 contribute to social reward in the habenula.Scientific reports · 2022Article
22 more citing papers are in PubMed but not listed here.
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10 authors at 4 institutions in 2 countries.
Funding
Abstract
Opiates are powerful drugs to treat severe pain, and act via mu opioid receptors distributed throughout the nervous system. Their clinical use is hampered by centrally-mediated adverse effects, including nausea or respiratory depression. Here we used a genetic approach to investigate the potential of peripheral mu opioid receptors as targets for pain treatment. We generated conditional knockout (cKO) mice in which mu opioid receptors are deleted specifically in primary afferent Nav1.8-positive neurons. Mutant animals were compared to controls for acute nociception, inflammatory pain, opiate-induced analgesia and constipation. There was a 76% decrease of mu receptor-positive neurons and a 60% reduction of mu-receptor mRNA in dorsal root ganglia of cKO mice. Mutant mice showed normal responses to heat, mechanical, visceral and chemical stimuli, as well as unchanged morphine antinociception and tolerance to antinociception in models of acute pain. Inflammatory pain developed similarly in cKO and controls mice after Complete Freund's Adjuvant. In the inflammation model, however, opiate-induced (morphine, fentanyl and loperamide) analgesia was reduced in mutant mice as compared to controls, and abolished at low doses. Morphine-induced constipation remained intact in cKO mice. We therefore genetically demonstrate for the first time that mu opioid receptors partly mediate opiate analgesia at the level of Nav1.8-positive sensory neurons. In our study, this mechanism operates under conditions of inflammatory pain, but not nociception. Previous pharmacology suggests that peripheral opiates may be clinically useful, and our data further demonstrate that Nav1.8 neuron-associated mu opioid receptors are feasible targets to alleviate some forms of persistent pain.
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