ArticleHeadache2021
A non-convulsant delta-opioid receptor agonist, KNT-127, reduces cortical spreading depression and nitroglycerin-induced allodynia.
Article in Headache, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- PN6047 Demonstrates Broad Preclinical Efficacy in Headache Models as a Novel Delta-Opioid Receptor Agonist.bioRxiv : the preprint server for biology · 2026Article
- Delta opioid receptor agonists activate PI3K-mTORC1 signaling in parvalbumin-positive interneurons in mouse infralimbic prefrontal cortex to exert acute antidepressant-lie effects.Molecular psychiatry · 2025Article
- Activation of δ-opioid receptors blocks allodynia in a model of headache induced by PACAP.British journal of pharmacology · 2025Article
- Opioid receptor signaling throughout ontogeny: Shaping neural and behavioral trajectories.Neuroscience and biobehavioral reviews · 2025Review
- Progesterone receptors regulate susceptibility to spreading depression.Experimental neurology · 2025Article
- GV16 acupoint stimulation with bee venom reduces peripheral hypersensitivity via activation of α2 adrenoceptors in a nitroglycerin-induced migraine mouse model.Integrative medicine research · 2023Article
- Receptor expression and signaling properties in the brain, and structural ligand motifs that contribute to delta opioid receptor agonist-induced seizures.Neuropharmacology · 2023Review
- Article
- PACAP-PAC1 receptor inhibition is effective in opioid induced hyperalgesia and medication overuse headache models.iScience · 2023Article
- Novel Therapeutic Targets for Migraine.Biomedicines · 2023Review
- Different Involvement of ASIC and TRPA1 in Facial and Hindpaw Allodynia in Nitroglycerin-Induced Peripheral Hypersensitivities in Mice.Life (Basel, Switzerland) · 2022Article
- Neuronal complexity is attenuated in preclinical models of migraine and restored by HDAC6 inhibition.eLife · 2021Article
- Cutaneous Allodynia in Migraine: A Narrative Review.Frontiers in neurology · 2021Review
- Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveThe aim of this study was to determine if the non-convulsant delta-opioid receptor (DOR) agonist, KNT-127, could inhibit migraine-associated endpoints.
backgroundThe DOR has been identified as a therapeutic target for migraine. However, the development of delta agonists is limited as some ligands have seizurogenic properties, which may be related to their ability to induce receptor internalization. While both pro- and non-convulsant delta agonists can reduce migraine-associated allodynia, only the proconvulsant agonist, SNC80, has been shown to decrease cortical spreading depression (CSD). It is unclear if the ability of delta agonists to modulate cortical activity is related to the same signaling mechanisms that produce proconvulsant effects.
methodsThe effects of the non-convulsant delta agonist, KNT-127, were examined. Repetitive CSD was induced in female C57BL6/J (n = 6/group) mice by continuous application of KCl and the effect of KNT-127/vehicle (Veh) on both local field potentials and optical intrinsic signals was determined. To assess the effect of KNT-127 on established chronic migraine-associated pain, male and female C57BL6/J mice were treated with nitroglycerin (NTG; 10 mg/kg, ip) every other day for 9 days and tested with KNT-127 (5 mg/kg, sc) or Veh on day 10 (n = 6/group). DOR-enhanced green fluorescent protein mice (n = 4/group) were used to confirm the internalization properties of KNT-127 in the trigeminal ganglia, trigeminal nucleus caudalis, and somatosensory cortex.
resultsKNT-127 inhibited CSD events (t
conclusionsThis study shows that the antimigraine effects of DOR agonists can be separated from their proconvulsant effects. This data provides valuable information for the continued development of delta agonists for the treatment of migraine.
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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.