ArticleBritish journal of pharmacology2016
Contribution of adrenomedullin to the switch of G protein-coupled μ-opioid receptors from Gi to Gs in the spinal dorsal horn following chronic morphine exposure in rats.
Article in British journal of pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 20 citations in OpenAlex.
- Persistent Mu-Opioid Receptor Dysregulation in a Pain-Facilitatory Brain Region Reinstates Hyperalgesia After Resolution of Opioid-Induced Hyperalgesia.Pharmaceuticals (Basel, Switzerland) · 2026Article
- De novo expression of neuropeptide Y in sensory neurons does not contribute to peripheral neuropathic pain.The journal of pain · 2025Article
- Diffuse Noxious Inhibitory Controls in Chronic Pain States: Insights from Pre-Clinical Studies.International journal of molecular sciences · 2025Review
- Neuropeptide Y Y2 receptors in acute and chronic pain and itch.Neuropeptides · 2024Review
- Additive Anticonvulsive Effects of Sumatriptan and Morphine on Pentylenetetrazole-Induced Clonic Seizures in Mice.Journal of epilepsy research · 2024Article
- Arbiters of endogenous opioid analgesia: role of CNS estrogenic and glutamatergic systems.Translational research : the journal of laboratory and clinical medicine · 2021Review
- Relevance of Mu-Opioid Receptor Splice Variants and Plasticity of Their Signaling Sequelae to Opioid Analgesic Tolerance.Cellular and molecular neurobiology · 2021Review
- Adrenomedullin increases cAMP accumulation and BDNF expression in rat DRG and spinal motor neurons.Iranian journal of basic medical sciences · 2021Article
- Addressing opioid tolerance and opioid-induced hypersensitivity: Recent developments and future therapeutic strategies.Pharmacology research & perspectives · 2021Review
- Disulfiram Abrogates Morphine Tolerance-A Possible Role of µ-Opioid Receptor-Related G-Protein Activation in the Striatum.International journal of molecular sciences · 2021Article
- Adrenomedullin: an important participant in neurological diseases.Neural regeneration research · 2020Review
- The Contribution of the Descending Pain Modulatory Pathway in Opioid Tolerance.Frontiers in neuroscience · 2018Article
- Contribution of adrenomedullin to the switch of G protein-coupled μ-opioid receptors from Gi to Gs in the spinal dorsal horn following chronic morphine exposure in rats.British journal of pharmacology · 2016Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeChronic exposure to morphine increases spinal adrenomedullin (AM) bioactivity resulting in the development and maintenance of morphine tolerance. This study investigated the possible involvement of AM in morphine-evoked alteration in μ-opioid receptor-coupled G proteins. EXPERIMENTAL APPROACH: Agents were administered intrathecally (i.t.) in rats. Nociceptive behaviours and cumulative dose-response of morphine analgesia were assessed. Neurochemicals in the spinal dorsal horn were assayed by immunoprecipitation, Western blot analysis and ELISA. KEY
resultsIntrathecal injection of AM (8 μg) for 9 days decreased and increased the levels of μ receptor-coupled Gi and Gs proteins respectively. Morphine stimulation (5 μg) after chronic treatment with AM also induced an increase in cAMP production in the spinal dorsal horn. Co-administration of the selective AM receptor antagonist AM22-52 inhibited chronic morphine-evoked switch of G protein-coupled μ receptor from Gi to Gs. Chronic exposure to AM increased the phosphorylation of cAMP-responsive element-binding protein (CREB) and ERK. Co-administration of the PKA inhibitor H-89 (5 μg) or MEK1 inhibitor PD98059 (1 μg) reversed the AM-induced thermal/mechanical hypersensitivity, decline in morphine analgesic potency, switch of G protein-coupled μ receptor and increase in cAMP. CONCLUSIONS AND IMPLICATIONS: The present study supports the hypothesis that an increase in AM activity in the spinal dorsal horn contributes to the switch of the μ receptor-coupled G protein from Gi to Gs protein via the activation of cAMP/PKA/CREB and ERK signalling pathways in chronic morphine use.
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