ArticleProceedings of the National Academy of Sciences of the United States of America2010
Morphine peripheral analgesia depends on activation of the PI3Kgamma/AKT/nNOS/NO/KATP signaling pathway.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 200 citations in OpenAlex.
- Targeting druggable kinases in neuropathic pain.npj drug discovery · 2026Review
- 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
- Dual CCR2/CCR5 Antagonism with Cenicriviroc Alleviates Nerve Injury-Induced Hypersensitivity and Prevents Morphine Tolerancevia Modulation of Neuroimmune Signaling.Cellular and molecular neurobiology · 2026Article
- Medicinal Plants That Modulate Nitric Oxide Synthase Activity: Implications in Inflammation and Oxidative Stress.Drug design, development and therapy · 2026Review
- Fructose-1,6-Bisphosphate Reduces Chronic Constriction Injury Neuropathic Pain in Mice by Targeting Dorsal Root Ganglia Nociceptive Neuron Activation.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Peripheral Opioid Receptors in the Modulation of Inflammatory Pain: a Narrative Review.Maedica · 2025Review
- Meningeal K ATP channels contribute to behavioral responses in preclinical migraine models.Pain · 2025Article
- Ablation of PI3Kγ in neurons protects mice from diet-induced obesity MASLD and insulin resistance.iScience · 2025Article
- Met-enkephalin modulates the stress responses of plasma concentrations of corticosterone, delta opioid receptor binding, pro-enkephalin expression, and processing in chickens.Frontiers in physiology · 2025Article
- Study on peripheral antinociception induced by hydrogen peroxide (HNaunyn-Schmiedeberg's archives of pharmacology · 2024Article
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- Loss of ATP-sensitive channel expression and function decreases opioid sensitivity in a mouse model of type 2 diabetes.bioRxiv : the preprint server for biology · 2023Article
- Article
- Kaurenoic Acid Reduces Ongoing Chronic Constriction Injury-Induced Neuropathic Pain: Nitric Oxide Silencing of Dorsal Root Ganglia Neurons.Pharmaceuticals (Basel, Switzerland) · 2023Article
- S-nitroso-L-cysteine stereoselectively blunts the adverse effects of morphine on breathing and arterial blood gas chemistry while promoting analgesia.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2022Article
- ATP-Sensitive Potassium Channels in Migraine: Translational Findings and Therapeutic Potential.Cells · 2022Review
- Design, synthesis and in vivo evaluation of 1,4-dioxo-2-butenyl aryl amine derivatives as a promising anti-inflammatory drug prototype.Bioorganic chemistry · 2022Article
- Flavonoids as Potential Anti-Inflammatory Molecules: A Review.Molecules (Basel, Switzerland) · 2022Review
- Dual PI3Kδ/γ Inhibitor Duvelisib Prevents Development of Neuropathic Pain in Model of Paclitaxel-Induced Peripheral Neuropathy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Morphine is one of the most prescribed and effective drugs used for the treatment of acute and chronic pain conditions. In addition to its central effects, morphine can also produce peripheral analgesia. However, the mechanisms underlying this peripheral action of morphine have not yet been fully elucidated. Here, we show that the peripheral antinociceptive effect of morphine is lost in neuronal nitric-oxide synthase null mice and that morphine induces the production of nitric oxide in primary nociceptive neurons. The activation of the nitric-oxide pathway by morphine was dependent on an initial stimulation of PI3Kgamma/AKT protein kinase B (AKT) and culminated in increased activation of K(ATP) channels. In the latter, this intracellular signaling pathway might cause a hyperpolarization of nociceptive neurons, and it is fundamental for the direct blockade of inflammatory pain by morphine. This understanding offers new targets for analgesic drug development.
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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.