ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
PI3-kinase/Akt pathway-regulated membrane insertion of acid-sensing ion channel 1a underlies BDNF-induced pain hypersensitivity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 96 citations in OpenAlex.
- Acid-sensing ion channels in ischemic stroke: amplifying and constraining neuronal injury in a phase-specific framework.Pflugers Archiv : European journal of physiology · 2026Review
- Spinal TREM2/PI3K/Akt signal axis elicits microglial activation and aggravates bone cancer pain.Journal of anesthesia and translational medicine · 2025Article
- Selective blockade of acid-sensing ion channel 1a can provide substantial hippocampal neuroprotection.Frontiers in cell and developmental biology · 2025Article
- Modulation of Brain-derived Neurotrophic Factor Expression by Physical Exercise in Reserpine-induced Pain-depression Dyad in Mice.Experimental neurobiology · 2024Article
- Insulin enhances acid-sensing ion channel currents in rat primary sensory neurons.Scientific reports · 2024Article
- Pathology of pain and its implications for therapeutic interventions.Signal transduction and targeted therapy · 2024Review
- The epithelial NaCell reports · 2023Article
- Analgesic efficacy of median nerve stimulation in mice with chemotherapy-induced peripheral neuropathymodulation of brain-derived neurotrophic factor expression.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Article
- Sonic Hedgehog Signaling Pathway: A Role in Pain Processing.Neurochemical research · 2023Review
- ASIC1α up-regulates MMP-2/9 expression to enhance mobility and proliferation of liver cancer cells via the PI3K/AKT/mTOR pathway.BMC cancer · 2022Article
- 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
- [ANA- 12 inhibits spinal inflammation and alleviates acute and chronic pain in rats by targeted blocking of BDNF/TrkB signaling].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Acid-sensing ion channel 1a in the central nucleus of the amygdala regulates anxiety-like behaviors in a mouse model of acute pain.Frontiers in molecular neuroscience · 2022Article
- C-Jun N-Terminal Kinase Post-Translational Regulation of Pain-Related Acid-Sensing Ion Channels 1b and 3.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- The M1 and pre-M1 segments contribute differently to ion selectivity in ASICs and ENaCs.The Journal of general physiology · 2021Article
- Translocation of TMEM175 Lysosomal Potassium Channel to the Plasma Membrane by Dynasore Compounds.International journal of molecular sciences · 2021Article
- Postsynaptic Targeting and Mobility of Membrane Surface-Localized hASIC1a.Neuroscience bulletin · 2021Article
- Hydrogen Sulfide Upregulates Acid-sensing Ion ChannelsFunction (Oxford, England) · 2021Article
- Signaling Pathways in Proton and Non-proton ASIC1a Activation.Frontiers in cellular neuroscience · 2021Article
- Role of Spinal Cord Akt-mTOR Signaling Pathways in Postoperative Hyperalgesia Induced by Plantar Incision in Mice.Frontiers in neuroscience · 2020Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Central neural plasticity plays a key role in pain hypersensitivity. This process is modulated by brain-derived neurotrophic factor (BDNF) and also involves the type 1a acid-sensing ion channel (ASIC1a). However, the interactions between the BDNF receptor, tropomyosin-related kinase B (TrkB), and ASIC1a are unclear. Here, we show that deletion of ASIC1 gene suppressed the sustained mechanical hyperalgesia induced by intrathecal BDNF application in mice. In both rat spinal dorsal horn neurons and heterologous cell cultures, the BDNF/TrkB pathway enhanced ASIC1a currents via phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB/Akt) cascade and phosphorylation of cytoplasmic residue Ser-25 of ASIC1a, resulting in enhanced forward trafficking and increased surface expression. Moreover, in both rats and mice, this enhanced ASIC1a activity was required for BDNF-mediated hypersensitivity of spinal dorsal horn nociceptive neurons and central mechanical hyperalgesia, a process that was abolished by intrathecal application of a peptide representing the N-terminal region of ASIC1a encompassing Ser-25. Thus, our results reveal a novel mechanism underlying central sensitization and pain hypersensitivity, and reinforce the critical role of ASIC1a channels in these processes.
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