ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
Pain after discontinuation of morphine treatment is associated with synaptic increase of GluA4-containing AMPAR in the dorsal horn of the spinal cord.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Cornichon Homolog-3 (Cnih3) deletion impairs spatial memory, operant learning, and fentanyl self-administration behavior.Translational psychiatry · 2026Article
- A role for leucine-rich, glioma inactivated 1 in regulating pain sensitivity.Brain : a journal of neurology · 2025Article
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- Endogenous opioid systems alterations in pain and opioid use disorder.Frontiers in systems neuroscience · 2022Review
- Vezatin regulates seizures by controlling AMPAR-mediated synaptic activity.Cell death & disease · 2021Article
- Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model.Frontiers in synaptic neuroscience · 2021Article
- Synthesis and Pharmacology of a Novel μ-δ Opioid Receptor Heteromer-Selective Agonist Based on the Carfentanyl Template.Journal of medicinal chemistry · 2020Article
- Mu and delta opioid receptors play opposite nociceptive and behavioural roles on nerve-injured mice.British journal of pharmacology · 2020Article
- Analgesic and Anti-Inflammatory Effects of Perampanel in Acute and Chronic Pain Models in Mice: Interaction With the Cannabinergic System.Frontiers in pharmacology · 2020Article
- Sigma-1 receptor modulates neuroinflammation associated with mechanical hypersensitivity and opioid tolerance in a mouse model of osteoarthritis pain.British journal of pharmacology · 2019Article
- Opioid receptors inhibit the spinal AMPA receptor CaExperimental neurology · 2019Article
- Neonatal Clonazepam Administration Induces Long-Lasting Changes in Glutamate Receptors.Frontiers in molecular neuroscience · 2018Article
- Inflammation-induced GluA1 trafficking and membrane insertion of CaExperimental neurology · 2017Article
- What Is Being Trained? How Divergent Forms of Plasticity Compete To Shape Locomotor Recovery after Spinal Cord Injury.Journal of neurotrauma · 2017Review
- Identification of an epidermal keratinocyte AMPA glutamate receptor involved in dermatopathies associated with sensory abnormalities.Pain reports · 2016Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Withdrawal from prescribed opioids results in increased pain sensitivity, which prolongs the treatment. This pain sensitivity is attributed to neuroplastic changes that converge at the spinal cord dorsal horn. We have recently reported that repeated morphine administration triggers an insertion of GluA2-lacking (Ca(2+)-permeable) α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPAR) in the hippocampus. This finding together with the reported involvement of AMPAR in the mechanisms underlying inflammatory pain led us to hypothesize a role for spinal AMPAR in opioid-induced pain behavior. Mice treated with escalating doses of morphine showed hypersensitivity to mechanical stimulation. Intrathecal administration of a Ca(2+)-permeable AMPAR selective blocker disrupted morphine-induced mechanical sensitivity. Analysis of the expression and phosphorylation levels of AMPAR subunits (GluA1/2/3/4) in homogenates and in postsynaptic density fractions from spinal cord dorsal horns showed an increase in GluA4 expression and phosphorylation in the postsynaptic density after morphine. Co-immunoprecipitation analyses suggested an increase in GluA4 homomers (Ca(2+)-permeable AMPAR) and immunohistochemical staining localized the increase in GluA4 levels in laminae III-V. The excitatory postsynaptic currents (EPSCs) recorded in laminae III-V showed enhanced sensitivity to Ca(2+)-permeable AMPAR blockers in morphine-treated mice. Furthermore, current-voltage relationships of AMPAR-mediated EPSCs showed that rectification index (an indicator of Ca(2+)-permeable AMPAR contribution) is increased in morphine-treated but not in saline-treated mice. These effects could be reversed by infusion of GluA4 antibody through patch pipette. This is the first direct evidence for a role of GluA4-containing AMPAR in morphine-induced pain and highlights spinal GluA4-containing AMPAR as targets to prevent the morphine-induced pain sensitivity.
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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.