Transient receptor potential melastatin 8 is required for nitroglycerin- and calcitonin gene-related peptide–induced migraine-like pain behaviors in mice

Wei, Chao; Kim, Brian; McKemy, David D.

doi:10.1097/j.pain.0000000000002635

Cited by 16 publications

(5 citation statements)

References 70 publications

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“…Both drugs were delivered through intraperitoneal route in all experiments. NTG-induced acute migraine model with a dose of 10 mg/kg is already extensively validated by many studies [ 8 , 27 – 29 ], therefore, we adopted the same dose for our study. For LVC-induced acute migraine model, we administered 1 mg/kg LVC, a dose used in an LVC-induced chronic migraine model [ 30 ].…”

Section: Methodsmentioning

confidence: 99%

Levcromakalim provokes an acute rapid-onset migraine-like phenotype without inducing cortical spreading depolarization

Alpay¹,

Cimen²,

Akaydin³

et al. 2023

J Headache Pain

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Background Migraine 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. Methods Wistar 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. Results LVC 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. Conclusions Single 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+ channel opening properties of LVC. Understanding the neurobiological mechanisms of this nociceptive window, may provide a novel target in migraine treatment.

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Section: Methodsmentioning

confidence: 99%

Levcromakalim provokes an acute rapid-onset migraine-like phenotype without inducing cortical spreading depolarization

Alpay¹,

Cimen²,

Akaydin³

et al. 2023

J Headache Pain

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“…A recent study using transgenic knockout TRPM8 mice suggests a protective role in promoting a faster recovery from chronic migraine-like symptoms in male mice compared to that in female mice [126]. However, another study with transgenic mice showed that TRPM8 channels or afferents are both required for the development of acute and chronic migrainelike symptoms [127]. This suggests that further investigations are needed to determine the role and therapeutic potential of TRPM8.…”

Section: Trp Channels As Targets For Anti-migraine Drugsmentioning

confidence: 99%

Targeting Nociceptive Neurons and Transient Receptor Potential Channels for the Treatment of Migraine

Cohen

Roh

Lee

et al. 2023

IJMS

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Migraine is a neurovascular disorder that affects approximately 12% of the global population. While its exact causes are still being studied, researchers believe that nociceptive neurons in the trigeminal ganglia play a key role in the pain signals of migraine. These nociceptive neurons innervate the intracranial meninges and convey pain signals from the meninges to the thalamus. Targeting nociceptive neurons is considered promising due to their accessibility and distinct molecular profile, which includes the expression of several transient receptor potential (TRP) channels. These channels have been linked to various pain conditions, including migraine. This review discusses the role and mechanisms of nociceptive neurons in migraine, the challenges of current anti-migraine drugs, and the evidence for well-studied and emerging TRP channels, particularly TRPC4, as novel targets for migraine prevention and treatment.

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“…A recent study using transgenic knockout TRPM8 mice suggests a protective role in promoting a faster recovery from chronic migraine-like symptoms in male mice compared to that in female mice [115]. However, another study with transgenic mice showed that TRPM8 channels or afferents are both required for the development of acute and chronic migraine-like symptoms [116]. This suggests that further investigations are needed to determine the role and therapeutic potential of TRPM8.…”

Section: Trpm8mentioning

confidence: 99%

Targeting Nociceptors and Transient Receptor Potential Channels for the Treatment of Migraine

Cohen¹,

Roh²,

Lee³

2023

Preprint

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Migraine is a neurovascular disorder that affects approximately 12% of the global population. While its exact causes are still being studied, researchers believe that nociceptors in the trigeminal ganglia play a key role in the pain signals of migraine. These nociceptors innervate the intracranial meninges and convey pain signals from the meninges to the thalamus. Targeting these nociceptors is considered promising due to their accessibility and distinct molecular profile, which includes the expression of several transient receptor potential (TRP) channels. These channels have been linked to various pain conditions, including migraine. This review discusses the role and mechanisms of nociceptors in migraine, the challenges of current antimigraine drugs, and the evidence for well-studied and emerging TRP channels, particularly TRPC4, as novel targets for migraine prevention and treatment.

show abstract

Transient receptor potential melastatin 8 is required for nitroglycerin- and calcitonin gene-related peptide–induced migraine-like pain behaviors in mice

Cited by 16 publications

References 70 publications

Levcromakalim provokes an acute rapid-onset migraine-like phenotype without inducing cortical spreading depolarization

Levcromakalim provokes an acute rapid-onset migraine-like phenotype without inducing cortical spreading depolarization

Targeting Nociceptive Neurons and Transient Receptor Potential Channels for the Treatment of Migraine

Targeting Nociceptors and Transient Receptor Potential Channels for the Treatment of Migraine

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