ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
cAMP-mediated mechanisms for pain sensitization during opioid withdrawal.
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 40 papers.
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The trial behind it
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Who cites it
40 citing papers in PubMed, 88 citations in OpenAlex.
- Inhibition of adenylyl cyclase 1 or exchange protein activated by cAMP restores ATP-sensitive potassium channel activity after chronic opioid exposure.British journal of pharmacology · 2026Article
- Central amygdalar PKCδ neurons mediate fentanyl withdrawal.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Morphine-inducedFrontiers in neuroscience · 2026Article
- Identification of Anti-Inflammatory and Analgesic Mechanisms of Naru-3 Wei Pill Using Animal Models, UHPLC-QE-MS, and Integrated Network Pharmacology.Mediators of inflammation · 2026Article
- Review
- Molecular and cellular basis of mu-opioid receptor signaling: mechanisms underlying tolerance and dependence development.Frontiers in neuroscience · 2025Review
- Opioid-Induced Hyperalgesia and Tolerance Are Driven by HCN Ion Channels.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Opioid-Induced Reductions in Amygdala Lateral Paracapsular GABA Neuron Circuit Activity.International journal of molecular sciences · 2023Article
- Identifying the Neurodevelopmental Differences of Opioid Withdrawal.Cellular and molecular neurobiology · 2021Article
- Co-administration of nalbuphine attenuates the morphine-induced anxiety and dopaminergic alterations in morphine-withdrawn rats.Psychopharmacology · 2021Article
- The habenular G-protein-coupled receptor 151 regulates synaptic plasticity and nicotine intake.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Activation of mGluR1 Mediates C1q-Dependent Microglial Phagocytosis of Glutamatergic Synapses in Alzheimer's Rodent Models.Molecular neurobiology · 2019Article
- 2 Hz EA Reduces Heroin Withdrawal-Induced Hyperalgesia and Heroin Relapse by Downregulating P2X3 Receptors in DRG Neurons.BioMed research international · 2019Article
- Article
- Repeated Mu-Opioid Exposure Induces a Novel Form of the Hyperalgesic Priming Model for Transition to Chronic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Effects of Venlafaxine & Methadone Alone and in Combination with Spontaneous Morphine withdrawal Syndrome & Pain Sensation in Rats.Basic and clinical neuroscience · 2015Article
- Studies on the analgesic activities of Jia-Yuan-Qing pill and its safety evaluation in mice.Protoplasma · 2014Article
- Persistent inflammation-induced up-regulation of brain-derived neurotrophic factor (BDNF) promotes synaptic delivery of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA1 subunits in descending pain modulatory circuits.The Journal of biological chemistry · 2014Article
- Epigenetic suppression of neuroligin 1 underlies amyloid-induced memory deficiency.Nature neuroscience · 2014Article
- Brain-derived neurotrophic factor-mediated downregulation of brainstem K+-Cl- cotransporter and cell-type-specific GABA impairment for activation of descending pain facilitation.Molecular pharmacology · 2013Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chronic opioid-induced drug dependence and withdrawal syndrome after opioid cessation remain a severe obstacle in clinical treatment of chronic pain and opioid drug addiction. One of the key symptoms during opioid withdrawal is a state of sensitized pain. The most significant molecular adaptation induced by chronic opioids in the brain is upregulation of the cAMP-signaling pathway. Although the cAMP system is known to have multiple effects on central neuron functions, how its upregulation mediates behavioral opioid dependence and withdrawal-induced pain in vivo remains unclear. In this study, we demonstrate that withdrawal from chronic morphine significantly upregulates the mRNA level of adenylyl cyclase (AC) VI and VIII isoforms and immunoreactivity of ACV/VI in the nucleus raphe magnus (NRM), a brainstem site critically involved in opioid modulation of pain. In cellular studies of NRM neurons containing mu-opioid receptors, we show that morphine withdrawal significantly increases glutamate synaptic transmission via a presynaptic mechanism mediated by an upregulated cAMP pathway. Morphine withdrawal also enhances the hyperpolarization-activated current in these neurons by increased intracellular cAMP. Both of the withdrawal-induced cAMP actions increase the excitability of these mu-receptor-containing neurons, which are thought to facilitate spinal pain transmission. Furthermore, in morphine-dependent rats in vivo, blocking the cAMP pathway significantly reduces withdrawal-induced pain sensitization. These results illustrate neurobiological mechanisms for the cAMP-mediated withdrawal pain and provide potential therapeutic targets for the treatment of opioid dependence and withdrawal-related problems.
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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.