ArticleAnesthesiology2016
AMPAkines Target the Nucleus Accumbens to Relieve Postoperative Pain.
Article in Anesthesiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Hotspots and frontiers in chronic postoperative pain: a bibliometric analysis and review (2004-2025).Frontiers in medicine · 2026Pooled it
- A top-down neural circuit for affective-motivational responses of pain relief induced by electroacupuncture.Chinese medicine · 2026Article
- A Neural Circuit From Paraventricular Nucleus of the Thalamus to the Nucleus Accumbens Mediates Inflammatory Pain in Mice.Brain and behavior · 2025Article
- Review
- Pharmacological restoration of anti-nociceptive functions in the prefrontal cortex relieves chronic pain.Progress in neurobiology · 2021Article
- AMPAkines potentiate the corticostriatal pathway to reduce acute and chronic pain.Molecular brain · 2021Article
- Intracranial Pharmacotherapy and Pain Assays in Rodents.Journal of visualized experiments : JoVE · 2019Article
- The Impact and Mechanism of a Novel Allosteric AMPA Receptor Modulator LCX001 on Protection Against Respiratory Depression in Rodents.Frontiers in pharmacology · 2019Article
- Inhibition of the Prefrontal Projection to the Nucleus Accumbens Enhances Pain Sensitivity and Affect.Frontiers in cellular neuroscience · 2018Article
- AMPAkines and morphine provide complementary analgesia.Behavioural brain research · 2017Article
- Corticostriatal Regulation of Acute Pain.Frontiers in cellular neuroscience · 2017Article
- Reward Circuitry Plasticity in Pain Perception and Modulation.Frontiers in pharmacology · 2017Review
- Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAMPAkines augment the function of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the brain to increase excitatory outputs. These drugs are known to relieve persistent pain. However, their role in acute pain is unknown. Furthermore, a specific molecular and anatomic target for these novel analgesics remains elusive.
methodsThe authors studied the analgesic role of an AMPAkine, CX546, in a rat paw incision (PI) model of acute postoperative pain. The authors measured the effect of AMPAkines on sensory and depressive symptoms of pain using mechanical hypersensitivity and forced swim tests. The authors asked whether AMPA receptors in the nucleus accumbens (NAc), a key node in the brain's reward and pain circuitry, can be a target for AMPAkine analgesia.
resultsSystemic administration of CX546 (n = 13), compared with control (n = 13), reduced mechanical hypersensitivity (50% withdrawal threshold of 6.05 ± 1.30 g [mean ± SEM] vs. 0.62 ± 0.13 g), and it reduced depressive features of pain by decreasing immobility on the forced swim test in PI-treated rats (89.0 ± 15.5 vs. 156.7 ± 18.5 s). Meanwhile, CX546 delivered locally into the NAc provided pain-relieving effects in both PI (50% withdrawal threshold of 6.81 ± 1.91 vs. 0.50 ± 0.03 g; control, n = 6; CX546, n = 8) and persistent postoperative pain (spared nerve injury) models (50% withdrawal threshold of 3.85 ± 1.23 vs. 0.45 ± 0.00 g; control, n = 7; CX546, n = 11). Blocking AMPA receptors in the NAc with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione inhibited these pain-relieving effects (50% withdrawal threshold of 7.18 ± 1.52 vs. 1.59 ± 0.66 g; n = 8 for PI groups; 10.70 ± 3.45 vs. 1.39 ± 0.88 g; n = 4 for spared nerve injury groups).
conclusionsAMPAkines relieve postoperative pain by acting through AMPA receptors in the NAc.
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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.