ArticleBritish journal of anaesthesia2019
ROR2 modulates neuropathic pain via phosphorylation of NMDA receptor subunit GluN2B in rats.
Article in British journal of anaesthesia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- EGR2 Facilitates LPS-Elicited Microglial Inflammation and Inflammatory Pain by Transcriptionally Activating MRTO4.Neurochemical research · 2026Article
- Comorbidity Mechanism and Management of Chronic Low Back Pain and Major Depressive Disorder: From Neural Circuit Remodeling to Precision Medicine.Brain and behavior · 2026Review
- Wnt5a in keratinocytes contributes to complex regional pain syndrome through the activation of NR2B and MMP9 in rats.Regional anesthesia and pain medicine · 2026Article
- The influence of magnesium ions on the electrophysiological, analgesic, and BDNF-induced neuromodulation of morphine effects in diabetic rats.Frontiers in pharmacology · 2026Article
- Mesenchymal stem cells' exosomes alleviate chronic visceral pain through Nrf-2-mediated oxidative stress pathway in rats.Pain reports · 2025Article
- Elevated synaptic PKA activity and abnormal striatal dopamine signaling in Akap11 mutant mice, a genetic model of schizophrenia and bipolar disorder.Nature communications · 2025Article
- Elevated synaptic PKA activity and abnormal striatal dopamine signaling inbioRxiv : the preprint server for biology · 2025Article
- Shentong Zhuyu Decoction Alleviates Neuropathic Pain in Mice by Inhibiting the NMDAR-2B Receptor-Mediated CaMKII/CREB Signaling Pathway in GABAergic Neurons of the Interpeduncular Nucleus.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Astrocytic Ror2-induced imbalance in brain and gut homeostasis contributes to chronic post-thoracotomy pain.Frontiers in aging neuroscience · 2025Article
- RNA Interference Unleashed: Current Perspective of Small Interfering RNA (siRNA) Therapeutics in the Treatment of Neuropathic Pain.ACS pharmacology & translational science · 2024Review
- Potential Plausible Role of Stem Cell for Treating Depressive Disorder: a Retrospective Review.Molecular neurobiology · 2024Review
- Intraperitoneal 5-Azacytidine Alleviates Nerve Injury-Induced Pain in Rats by Modulating DNA Methylation.Molecular neurobiology · 2023Article
- Roles of Phosphorylation of N-Methyl-D-Aspartate Receptor in Chronic Pain.Cellular and molecular neurobiology · 2023Review
- Axon Guidance Molecules and Pain.Cells · 2022Review
- Modulation of colonic function in irritable bowel syndrome rats by electroacupuncture at ST25 and the neurobiological links between ST25 and the colon.Frontiers in neuroscience · 2022Article
- Proto-oncogene tyrosine-protein kinase SRC (Src) inhibition in microglia relieves neuroinflammation in neuropathic pain mouse models.Bioengineered · 2021Article
- Stem Cell Therapy for Modulating Neuroinflammation in Neuropathic Pain.International journal of molecular sciences · 2021Review
- Spinal Wnt5a Plays a Key Role in Spinal Dendritic Spine Remodeling in Neuropathic and Inflammatory Pain Models and in the Proalgesic Effects of Peripheral Wnt3a.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Stem Cells in the Treatment of Neuropathic Pain: Research Progress of Mechanism.Stem cells international · 2020Review
- Molecular Mechanisms of Glial Cells Related Signaling Pathways Involved in the Neuroinflammatory Response of Depression.Mediators of inflammation · 2020Review
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Authors and funding
6 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuropathic pain, a type of chronic pain as a result of direct central or peripheral nerve damage, is associated with significant quality of life and functional impairment. Its underlying mechanisms remain unclear. We investigated whether ROR2, a member of the receptor tyrosine kinase-like orphan receptor (ROR) family, participates in modulation of neuropathic pain.
methodsThermal hyperalgesia and mechanical allodynia were measured using radiant heat and von Frey filament testing. Immunofluorescence staining was used to detect expression of ROR2 in neuronal nuclei. Fos expression was determined by immunocytochemistry. Phosphorylation status was detected by western blot and immunoprecipitation. Small interfering RNA was used to knock down ROR2 expression.
resultsROR2 was upregulated and activated in spinal neurones after chronic constriction injury (CCI) in mice [1.3 (0.1) to 2.1 (0.1)-fold of sham, P<0.01] from Day 1-21. CCI induced significant demethylation of the CpG island in the ROR2 gene promoter [0.37 (0.06) vs 0.12 (0.03)% CpG methylation, P<0.001]. Knockdown of ROR2 in the spinal cord prevented and reversed CCI-induced pain behaviours and spinal neuronal sensitisation [Fos expression: 130 (12) vs 81 (8) cells, P<0.05; 120 (11) vs 70 (7) cells, P<0.05]. In contrast, activation of spinal ROR2 by intrathecal injection of Wnt5a induced pain behaviours and spinal neuronal sensitisation [Fos expression: 11 (1) vs 100 (12) cells, P<0.001] in wild-type mice. Furthermore, ROR2-mediated pain modulation required phosphorylation of N-methyl-D-aspartate receptor 2B subunit (GluN2B) at Ser 1303 and Tyr1472 by pathways involving protein kinase C (PKC) and Src family kinases. Intrathecal injection of GluN2B, PKC, or Src family kinase-specific inhibitors significantly attenuated Wnt5a-induced pain behaviours.
conclusionsROR2 in the spinal cord regulates neuropathic pain via phosphorylation of GluN2B, suggesting a potential target for prevention and relief of neuropathic pain.
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