ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Perturbing PSD-95 interactions with NR2B-subtype receptors attenuates spinal nociceptive plasticity and neuropathic pain.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Cationic Arginine-Rich Peptides (CARPs): A Novel Class of Neuroprotective Agents With a Multimodal Mechanism of Action.Frontiers in neurology · 2020Pooled it
- Recombinant dimeric PICK1 peptide inhibitors for long-term relief of chronic pain by AAV therapeutics.Cell reports. Medicine · 2026Article
- Melatonin Mitigates Central Sensitization and Nociplastic Pain in Spinal Cord and Dorsal Root Ganglia of FM Rat Model: Modulation of SIRT1/PGC-1α/MAPK/NF-κB Signaling.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Tat-NR2B9c prevent cognitive dysfunction in mice modeling Alzheimer's Disease induced by AβIBRO neuroscience reports · 2025Article
- Agmatine inhibits NMDA receptor-mediated calcium transients in mouse spinal cord dorsal horn via intact PSD95-nNOS signaling.The Journal of pharmacology and experimental therapeutics · 2024Article
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- Electroacupuncture ameliorates pain in cervical spondylotic radiculopathy rat by inhibiting the CaMKII/CREB/BDNF signaling pathway and regulating spinal synaptic plasticity.Brain and behavior · 2023Article
- Sexually dimorphic extracellular vesicle responses after chronic spinal cord injury are associated with neuroinflammation and neurodegeneration in the aged brain.Journal of neuroinflammation · 2023Article
- Chinese Tuina remodels the synaptic structure in neuropathic pain rats by downregulating the expression of N-methyl D-aspartate receptor subtype 2B and postsynaptic density protein-95 in the spinal cord dorsal horn.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2023Article
- MMG22 Potently Blocks Hyperalgesia in Cisplatin-treated Mice.Neuroscience · 2023Article
- Roles of Phosphorylation of N-Methyl-D-Aspartate Receptor in Chronic Pain.Cellular and molecular neurobiology · 2023Review
- Recent advances in the study of anesthesia-and analgesia-related mechanisms of S-ketamine.Frontiers in pharmacology · 2023Review
- Dimethyl Fumarate (DMF) Alleviated Post-Operative (PO) Pain through theAntioxidants (Basel, Switzerland) · 2022Article
- Life extension factor klotho regulates behavioral responses to stress via modulation of GluN2B function in the nucleus accumbens.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Effects of Repetitive Transcranial Magnetic Stimulation (rTMS) and Treadmill Training on Recovery of Motor Function in a Rat Model of Partial Spinal Cord Injury.Medical science monitor : international medical journal of experimental and clinical research · 2021Article
- Absence of RNA-binding protein FXR2P prevents prolonged phase of kainate-induced seizures.EMBO reports · 2021Article
- CaMKII binding to GluN2B at S1303 has no role in acute or inflammatory pain.Brain research · 2021Article
- A pain killer without analgesic tolerance designed by co-targeting PSD-95-nNOS interaction and α2-containning GABATheranostics · 2021Article
- A high-affinity, bivalent PDZ domain inhibitor complexes PICK1 to alleviate neuropathic pain.EMBO molecular medicine · 2020Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Peripheral inflammation or nerve injury induces a primary afferent barrage into the spinal cord, which can cause N-methyl D-aspartate (NMDA) receptor-dependent alterations in the responses of dorsal horn sensory neurons to subsequent afferent inputs. This plasticity, such as "wind-up" and central sensitization, contributes to the hyperexcitability of dorsal horn neurons and increased pain-related behavior in animal models, as well as clinical signs of chronic pain in humans, hyperalgesia and allodynia. Binding of NMDA receptor subunits by the scaffolding protein postsynaptic density protein-95 (PSD-95) can facilitate downstream intracellular signaling and modulate receptor stability, contributing to synaptic plasticity. Here, we show that spinal delivery of the mimetic peptide Tat-NR2B9c disrupts the interaction between PSD-95 and NR2B subunits in the dorsal horn and selectively reduces NMDA receptor-dependent events including wind-up of spinal sensory neurons, and both persistent formalin-induced neuronal activity and pain-related behaviors, attributed to central sensitization. Furthermore, a single intrathecal injection of Tat-NR2B9c in rats with established nerve injury-induced pain attenuates behavioral signs of mechanical and cold hypersensitivity, with no effect on locomotor performance. Thus, uncoupling of PSD-95 from spinal NR2B-containing NMDA receptors may prevent the neuronal plasticity involved in chronic pain and may be a successful analgesic therapy, reducing side effects associated with receptor blockade.
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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.