ArticleCNS neuroscience & therapeutics2014
A novel role of spinal astrocytic connexin 43: mediating morphine antinociceptive tolerance by activation of NMDA receptors and inhibition of glutamate transporter-1 in rats.
Article in CNS neuroscience & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- Astrocytes and Astrocyte-Derived Extracellular Conduits in Opiate-Mediated Neurological Disorders.Cells · 2025Review
- Glutamatergic systems in neuropathic pain and emerging non-opioid therapies.Pharmacological research · 2022Review
- SUMOylation of Kir7.1 participates in neuropathic pain through regulating its membrane expression in spinal cord neurons.CNS neuroscience & therapeutics · 2022Article
- Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development.Pharmacological reviews · 2021Review
- Simultaneous Activation of Mu and Delta Opioid Receptors Reduces Allodynia and Astrocytic Connexin 43 in an Animal Model of Neuropathic Pain.Molecular neurobiology · 2019Article
- Inflammatory mediators of opioid tolerance: Implications for dependency and addiction.Peptides · 2019Review
- Morphine Dependence is Attenuated by Treatment of 3,4,5-Trimethoxy Cinnamic Acid in Mice and Rats.Neurochemical research · 2019Article
- The Emerging Perspective of Morphine Tolerance: MicroRNAs.Pain research & management · 2019Review
- Connexin Hemichannels in Astrocytes: Role in CNS Disorders.Frontiers in molecular neuroscience · 2019Review
- Selective blockade of spinal D2DR by levo-corydalmine attenuates morphine tolerance via suppressing PI3K/Akt-MAPK signaling in a MOR-dependent manner.Experimental & molecular medicine · 2018Article
- Cx43 and NMDA receptors changes in UL122 genetically modified mice hippocampus: a mechanism for spatial memory impairment.International journal of clinical and experimental pathology · 2018Article
- Inhibition of Connexin 43 and Phosphorylated NR2B in Spinal Astrocytes Attenuates Bone Cancer Pain in Mice.Frontiers in cellular neuroscience · 2018Article
- Astrocytic hypertrophy in the rat ventral tegmental area following chronic morphine differs with age.Journal of neurology and neurorehabilitation research · 2018Article
- Potentiation of spinal glutamatergic response in the neuron-glia interactions underlies the intrathecal IL-1β-induced thermal hyperalgesia in rats.CNS neuroscience & therapeutics · 2017Article
- Breakthrough Cancer Pain Is Associated with Spinal Gap Junction Activation via Regulation of Connexin 43 in a Mouse Model.Frontiers in cellular neuroscience · 2017Article
- Blockade of neuronal dopamine D2 receptor attenuates morphine tolerance in mice spinal cord.Scientific reports · 2016Article
- Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation.Trends in pharmacological sciences · 2016Review
- Morphine dependence is attenuated by red ginseng extract and ginsenosides Rh2, Rg3, and compound K.Journal of ginseng research · 2016Article
- Neuroprotective Effects of Dexmedetomidine Against Hypoxia-Induced Nervous System Injury are Related to Inhibition of NF-κB/COX-2 Pathways.Cellular and molecular neurobiology · 2016Article
- Microinjection of calcitonin in midbrain periaqueductal gray attenuates hyperalgesia in a chronic constriction injury rat model.Iranian journal of basic medical sciences · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsConnexin 43 (Cx43) has been reported to be involved in neuropathic pain, but whether it contributes to morphine antinociceptive tolerance remains unknown. The present study investigated the role of spinal Cx43 in the development of morphine tolerance and its mechanisms in rats.
methodsMorphine tolerance was induced by intrathecal (i.t.) administration of morphine (15 μg) daily for seven consecutive days. The analgesia effect was assessed by hot-water tail-flick test. Expression of proteins was detected by Western blot and immunohistochemistry assay.
resultsChronic morphine markedly increased the expression of spinal Cx43. Gap26, a specific Cx43 mimic peptide, attenuated not only morphine antinociceptive tolerance, but also the up-regulation of spinal Cx43 expression, the activation of astrocytes, and N-methyl-D-aspartic acid (NMDA) receptors (NR1 and NR2B subunits), as well as the decreased GLT-1 expression induced by chronic morphine. MK-801, a noncompetitive NMDA receptors antagonist, suppressed the chronic morphine-induced spinal Cx43 up-regulation, astrocytes activation and decline of GLT-1 expression.
conclusionsThe spinal astrocytic Cx43 contributes to the development of morphine antinociceptive tolerance by activating astrocytes and NMDA receptors, and inhibiting GLT-1 expression. We also demonstrate that the role of interaction between the spinal astrocytic Cx43 and neuronal NMDA receptors is important in morphine tolerant rats.
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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.