Auricular Electrical Stimulation Alleviates Headache through CGRP/COX-2/TRPV1/TRPA1 Signaling Pathways in a Nitroglycerin-Induced Migraine Rat Model

Liao, Chung-Chih; Li, Jung-Miao; Hsieh, Ching-Liang

doi:10.1155/2019/2413919

Cited by 7 publications

(5 citation statements)

References 63 publications

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“…Two members of the TRP superfamily are TRPA1 and TRPV1 channels, and they are also activated by OS [8,13]. The involvements of TRPA1 and TRPV1 on the GTNmediated migraine and pain models were recently reported [55][56][57]. Within the OS-dependent-activated TRP channels, TRPM2 is first discovered channel [15,16].…”

Section: Discussionmentioning

confidence: 99%

Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis

Yazğan

Nazıroğlu

2021

Mol Neurobiol

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Excessive Ca 2+ influx and mitochondrial oxidative stress (OS) of trigeminal ganglia (TG) have essential roles in the etiology of migraine headache and aura. The stimulation of TRPM2 channel via the generation of OS and ADP-ribose (ADPR) induces pain, inflammatory, and oxidative neurotoxicity, although its inhibition reduces the intensity of pain and neurotoxicity in several neurons. However, the cellular and molecular effects of TRPM2 in the TG of migraine model (glyceryl trinitrate, GTN) on the induction of pain, OS, apoptosis, and inflammation remain elusive. GTN-mediated increases of pain intensity, apoptosis, death, cytosolic reactive oxygen species (ROS), mitochondrial ROS, caspase -3, caspase -9, cytosolic Ca 2+ levels, and cytokine generations (TNF-α, IL-1β, and IL-6) in the TG of TRPM2 wild-type mouse were further increased by the TRPM2 activation, although they were modulated by the treatments of GSH, PARP-1 inhibitors (PJ34 and DPQ), and TRPM2 blockers (ACA and 2APB). However, the effects of GTN were not observed in the TG of TRPM2 knockout mice. The current data indicate that the maintaining activation of TRPM2 is not only important for the quenching OS, inflammation, and neurotoxicity in the TG neurons of mice with experimental migraine but also equally critical to the modulation of GTN-induced pain.

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Section: Discussionmentioning

confidence: 99%

Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis

Yazğan

Nazıroğlu

2021

Mol Neurobiol

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“…Within the NTG model, TRPA1 activation is probably caused by either nitric oxide or reactive oxygen species and inflammatory mediators [23,[38][39][40], all of which increase after the NTG challenge [17,[41][42][43][44]. Accordingly, previous studies reported increased TRPA1 gene expression and immunoreactivity in the TGs of NTG-treated rats [16,45].…”

Section: Trpa1 Antagonism In Migraine-like Painmentioning

confidence: 95%

Modulation of Glia Activation by TRPA1 Antagonism in Preclinical Models of Migraine

Demartini

Greco²,

Magni³

et al. 2022

IJMS

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Preclinical data point to the contribution of transient receptor potential ankyrin 1 (TRPA1) channels to the complex mechanisms underlying migraine pain. TRPA1 channels are expressed in primary sensory neurons, as well as in glial cells, and they can be activated/sensitized by inflammatory mediators. The aim of this study was to investigate the relationship between TRPA1 channels and glial activation in the modulation of trigeminal hyperalgesia in preclinical models of migraine based on acute and chronic nitroglycerin challenges. Rats were treated with ADM_12 (TRPA1 antagonist) and then underwent an orofacial formalin test to assess trigeminal hyperalgesia. mRNA levels of pro- and anti-inflammatory cytokines, calcitonin gene-related peptide (CGRP) and glia cell activation were evaluated in the Medulla oblongata and in the trigeminal ganglia. In the nitroglycerin-treated rats, ADM_12 showed an antihyperalgesic effect in both acute and chronic models, and it counteracted the changes in CGRP and cytokine gene expression. In the acute nitroglycerin model, ADM_12 reduced nitroglycerin-induced increase in microglial and astroglial activation in trigeminal nucleus caudalis area. In the chronic model, we detected a nitroglycerin-induced activation of satellite glial cells in the trigeminal ganglia that was inhibited by ADM_12. These findings show that TRPA1 antagonism reverts experimentally induced hyperalgesia in acute and chronic models of migraine and prevents multiple changes in inflammatory pathways by modulating glial activation.

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“…Although animals are not verbal, recent studies have considered NTG-induced animal models as clinically relevant due to the translational ability of behavioural endpoints [ 12 , 21 ]. Our previous studies showed that NTG-induced nociceptive behaviours in rats with migraine headache included reduced exploratory and locomotor behaviours and increased resting behaviour [ 33 , 34 ]. The aforementioned nociceptive behaviours in rodents mimicked those experienced by people with migraine, who generally present with reduced involvement in routine physical activity and decreased interest in exploring new surroundings or objects during an acute migraine attack episode [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies showed that NTG-induced nociceptive behaviours in rats with migraine headache included reduced exploratory and locomotor behaviours and increased resting behaviour [ 33 , 34 ]. The aforementioned nociceptive behaviours in rodents mimicked those experienced by people with migraine, who generally present with reduced involvement in routine physical activity and decreased interest in exploring new surroundings or objects during an acute migraine attack episode [ 34 , 35 ]. Therefore, we could use the parameters of the rat model to test antianalgesic drug potency.…”

Section: Discussionmentioning

confidence: 99%

The Effectiveness of Scutellaria baicalensis on Migraine: Implications from Clinical Use and Experimental Proof

Liao

Lin

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Background. Scutellaria baicalensis (SB), a traditional Chinese medicine, is commonly used for the treatment of inflammatory and painful conditions. The purpose of the present study was to examine the effects of SB on migraine. Materials and Methods. We examined the clinical applications of SB based on the data obtained from Taiwan’s National Health Insurance Research Database and confirmed that it was frequently used in Taiwan for the treatment of headaches. An experimental migraine model was established in rats by an intraperitoneal injection of nitroglycerin (NTG, 10 mg/kg). Pretreatment with SB was given orally 30 min before NTG administration. The rats were subjected to migraine-related behaviour tests that were video-recorded and analysed using EthoVision XT 12.0 software. Results. The frequency of exploratory and locomotor behaviour was comparatively lower in the NTG group than that in the control group, while the frequency of resting and grooming behaviour increased. These phenomena were ameliorated by pretreatment with 1.0 g/kg SB. The total time spent on the smooth surface was longer in the NTG group than that in the control group, but the time was shortened by pretreatment with 1.0 g/kg SB. Conclusions. Pretreatment with 1.0 g/kg SB relieved migraine-related behaviours in the experimental NTG-induced migraine model. The outcome therefore demonstrated that pretreatment with 1.0 g/kg SB is beneficial for migraine treatment.

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Auricular Electrical Stimulation Alleviates Headache through CGRP/COX-2/TRPV1/TRPA1 Signaling Pathways in a Nitroglycerin-Induced Migraine Rat Model

Cited by 7 publications

References 63 publications

Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis

Involvement of TRPM2 in the Neurobiology of Experimental Migraine: Focus on Oxidative Stress and Apoptosis

Modulation of Glia Activation by TRPA1 Antagonism in Preclinical Models of Migraine

The Effectiveness of Scutellaria baicalensis on Migraine: Implications from Clinical Use and Experimental Proof

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