ArticleCell death & disease2020
Persistent Rheb-induced mTORC1 activation in spinal cord neurons induces hypersensitivity in neuropathic pain.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
- From the Pain Matrix to Functional Networks: A Narrative Review of Chronic Pain Mechanisms Across Adult and Pediatric Populations with Emerging AI Perspectives.Brain sciences · 2026Review
- Network Pharmacology and Experimental Validation Unravel How Puerarin Improves Chronic Postoperative Pain.Molecular biotechnology · 2026Article
- Seizures exacerbate excitatory: inhibitory imbalance in Alzheimer's disease and 5XFAD mice.Brain : a journal of neurology · 2024Article
- Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury.Frontiers in pharmacology · 2024Article
- Epigenetic combined with transcriptomic analysis of the m6A methylome after spared nerve injury-induced neuropathic pain in mice.Neural regeneration research · 2023Article
- IGF/mTORC1/S6 Signaling Is Potentiated and Prolonged by Acute Loading of Subtoxicological Manganese Ion.Biomolecules · 2023Article
- Proteomic Analysis of the Spinal Dorsal Horn in Mice with Neuropathic Pain After Exercise.Journal of pain research · 2023Article
- The mTOR inhibitor rapamycin suppresses trigeminal neuropathic pain and p-MKK4/p-p38 mitogen-activated protein kinase-mediated microglial activation in the trigeminal nucleus caudalis of mice with infraorbital nerve injury.Frontiers in molecular neuroscience · 2023Article
- Increased miR-155 in Microglial Exosomes Following Heat Stress Accelerates Neuronal AutophagyFrontiers in cellular neuroscience · 2022Article
- Dexmedetomidine Alleviates Neuropathic Pain via the TRPC6-p38 MAPK Pathway in the Dorsal Root Ganglia of Rats.Journal of pain research · 2022Article
- Roles of AMPK and Its Downstream Signals in Pain Regulation.Life (Basel, Switzerland) · 2021Review
- Neuropathic Pain Creates Systemic Ultrastructural Changes in the Nervous System Corrected by Electroacupuncture but Not by Pregabalin.Journal of pain research · 2021Article
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
The small GTPase Ras homolog enriched in the brain (Rheb) can activate mammalian target of rapamycin (mTOR) and regulate the growth and cell cycle progression. We investigated the role of Rheb-mediated mTORC1 signaling in neuropathic pain. A chronic constriction injury (CCI) model was dopted. CCI induced obvious spinal Rheb expression and phosphorylation of mTOR, S6, and 4-E-BP1. Blocking mTORC1 signal with rapamycin alleviated the neuropathic pain and restored morphine efficacy in CCI model. Immunofluoresence showed a neuronal co-localization of CCI-induced Rheb and pS6. Rheb knockin mouse showed a similar behavioral phenotype as CCI. In spinal slice recording, CCI increased the firing frequency of neurons expressing HCN channels; inhibition of mTORC1 with rapamycin could reverse the increased spinal neuronal activity in neuropathic pain. Spinal Rheb is induced in neuropathic pain, which in turn active the mTORC1 signaling in CCI. Spinal Rheb-mTOR signal plays an important role in regulation of spinal sensitization in neuropathic pain, and targeting mTOR may give a new strategy for pain management.
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