ArticleNeuroscience2010
A cyclic peptide targeted against PSD-95 blocks central sensitization and attenuates thermal hyperalgesia.
Article in Neuroscience, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 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
- PSD-95 Protein: A Promising Therapeutic Target in Chronic Pain.Molecular neurobiology · 2025Review
- Structure-based design of peptidomimetic inhibitors of PSD-95 with improved affinity for the PDZ3 domain.FEBS letters · 2024Article
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Chronic pain following spinal cord injury: Current approaches to cellular and molecular mechanisms.Trends in cell & molecular biology · 2018Article
- TrkB-enhancer facilitates functional recovery after traumatic brain injury.Scientific reports · 2017Article
- Posttranslational Modifications Regulate the Postsynaptic Localization of PSD-95.Molecular neurobiology · 2017Review
- Inhibition of N-Methyl-D-aspartate-induced Retinal Neuronal Death by Polyarginine Peptides Is Linked to the Attenuation of Stress-induced Hyperpolarization of the Inner Mitochondrial Membrane Potential.The Journal of biological chemistry · 2015Article
- Unexpected Heterodivalent Recruitment of NOS1AP to nNOS Reveals Multiple Sites for Pharmacological Intervention in Neuronal Disease Models.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Serotonin-glutamate and serotonin-dopamine reciprocal interactions as putative molecular targets for novel antipsychotic treatments: from receptor heterodimers to postsynaptic scaffolding and effector proteins.Psychopharmacology · 2013Review
- An in silico analysis of the binding modes and binding affinities of small molecule modulators of PDZ-peptide interactions.PloS one · 2013Article
- Impairment of TrkB-PSD-95 signaling in Angelman syndrome.PLoS biology · 2013Article
- Time-dependent cross talk between spinal serotonin 5-HT2A receptor and mGluR1 subserves spinal hyperexcitability and neuropathic pain after nerve injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2012Article
- A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Perturbing PSD-95 interactions with NR2B-subtype receptors attenuates spinal nociceptive plasticity and neuropathic pain.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
- Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Post-synaptic density protein PSD-95 is emerging as a valid target for modulating nociception in animal studies. Based on the key role of PSD-95 in neuronal plasticity and the maintenance of pain behavior, we predicted that CN2097, a peptide-based macrocycle of nine residues that binds to the PSD-95 Discs large, Zona occludens 1 (PDZ) domains of PSD-95, would interfere with physiologic phenomena in the spinal cord related to central sensitization. Furthermore, we tested whether spinal intrathecal injection of CN2097 attenuates thermal hyperalgesia in a rat model of sciatic neuropathy. Results demonstrate that spinal CN2097 reverses hyperexcitability of wide dynamic range (WDR) neurons in the dorsal horn of neuropathic rats and decreases their evoked responses to peripheral stimuli (brush, low caliber von Frey and pressure), whereas CN5125 ("negative control") has no effect. CN2097 also blocks C-fiber long-term potentiation (LTP) in the dorsal horn, which is linked to neuronal plasticity and central sensitization. At a molecular level, CN2097 attenuates the increase in phosphorylated p38 MAPK, a key intracellular signaling pathway in neuropathic pain. Moreover, spinal injection of CN2097 blocks thermal hyperalgesia in neuropathic rats. We conclude that CN2097 is a small molecule peptide with putative anti-nociceptive effects that modulates physiologic phenomena related to central sensitization under conditions of chronic pain.
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Registered trials
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.