ArticleThe journal of headache and pain2023
Levcromakalim provokes an acute rapid-onset migraine-like phenotype without inducing cortical spreading depolarization.
Article in The journal of headache and pain, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 14 citations in OpenAlex.
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Diffusion Tensor Imaging-Based Glymphatic Dysfunction Assessments in Migraine Syndromes: Mechanisms and Diagnostic Implications.Biomedicines · 2025Review
- Is canonical SD a clinically relevant model of migraine? Argument con.The journal of headache and pain · 2025Review
- [A neural circuit from paraventricular hypothalamic nucleus oxytocin neurons to trigeminal nucleus caudalis GABAergic neurons modulates pain sensitization in a mouse model of chronic migraine].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2025Article
- Possible Role of Novel Mitochondrial Subsets in Migraine.Life (Basel, Switzerland) · 2025Review
- Extrasynaptic δGABAA receptors mediate resistance to migraine-like phenotype in rats.The journal of headache and pain · 2024Article
- Medication overuse headache is associated with elevated lipopolysaccharide binding protein and pro-inflammatory molecules in the bloodstream.The journal of headache and pain · 2023Article
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5 authors at 1 institution in 1 country.
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Abstract
backgroundMigraine headache attacks and accompanying sensory augmentation can be induced by several agents including levcromakalim (LVC), that is also capable of provoking aura-like symptoms in migraineurs. We investigated whether single LVC injection causes acute migraine-like phenotype in rats and induces/modulates cortical spreading depolarization (CSD), a rodent model of migraine aura.
methodsWistar rats were administered LVC (1 mg/kg, i.p.) and compared to control (CTRL, vehicle, i.p.) and nitroglycerin (NTG, 10 mg/kg, i.p.) groups. Von Frey filaments were used to examine the periorbital and hind paw mechanical allodynia. Dark-light box (DLB), elevated plus maze (EPM), and open field arena (OFA) were used to evaluate light sensitivity and anxiety-related behaviors. The effects of LVC on CSD parameters, somatosensory evoked potentials, and baseline dural EEG (electroencephalography) were investigated. Possible CSD-induced c-fos expression was studied with Western Blot. Blood-brain barrier integrity in cortex was examined with Evans blue assay.
resultsLVC and NTG administration robustly reduced periorbital mechanical thresholds in rats and induced anxiety-like behaviors and photophobia within 30 and 120 min, respectively. LVC induced migraine-like phenotype recovered in 2 h while NTG group did not fully recover before 4 h. Both LVC and NTG did not provoke DC (direct current) shift, EEG alterations or cortical c-fos expression characteristic to CSD. LVC did not induce de novo CSD and affect KCl (potassium chloride)-induced CSD parameters except for an increase in propagation failure. However, NTG significantly increased both CSD susceptibility and propagation failure. Somatosensory evoked potential (SSEP) configurations were not altered in both LVC and NTG groups, but SSEP latencies were prolonged after CSD. Acute LVC or NTG injection did not increase cortical BBB permeability.
conclusionsSingle LVC administration induced the fastest manifestation and recovery of acute migraine-like phenotype which was not mediated by CSD waves in the cerebral cortex. We suppose LVC triggered rapid-onset migraine-like symptoms are probably related to functional alterations in the trigeminal nociceptive system and K
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