Utility of different outcome measures for the nitroglycerin model of migraine in mice

Farkas, Sándor; Bölcskei, Kata; Markovics, Adrienn; Varga, Anita; Kis-Varga, Ágnes; Kormos, Viktória; Gaszner, Balázs; Horvath, C; Tuka, Bernadett; Tajti, János; Helyes, Zsuzsanna

doi:10.1016/j.vascn.2015.09.006

Cited by 45 publications

(55 citation statements)

References 67 publications

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“…Other researchers use special restrainers or cages to measure the orofacial thresholds in mice to overcome the challenges of handling-induced stress [107,108]. We have previously used the technique in NMRI mice [109], but in our experience C57Bl/6 mice tolerated this type of restraint less compared to the light manual handling. Changes in spontaneous behavior measured in the open field test corroborated previous results of our group regarding the possible role of HK-1 in mediating anxiolytic actions [40], but we could not detect any pain-induced reduction of spontaneous activity either (Supplementary Figure S1b).…”

Section: Discussionmentioning

confidence: 97%

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Aczél

Kecskés

Kun

et al. 2020

IJMS

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A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from the central terminals of primary afferents sensitize the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization in chronic orofacial pain and migraine. In the present study, we investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) encoded by the Tac4 gene in the trigeminal system. HK-1 had been shown to participate in inflammation and hyperalgesia in various models, but its role has not been investigated in orofacial pain or headache. In the complete Freund’s adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that Tac4 expression increased in the TG in response to inflammation. Duration-dependent Tac4 upregulation was associated with the extent of the facial allodynia. Tac4 was detected in both TG neurons and satellite glial cells (SGC) by the ultrasensitive RNAscope in situ hybridization. We also compared gene expression changes of selected neuronal and glial sensitization and neuroinflammation markers between wild-type and Tac4-deficient (Tac4-/-) mice. Expression of the SGC/astrocyte marker in the TG and TNC was significantly lower in intact and saline/CFA-treated Tac4-/- mice. The procedural stress-related increase of the SGC/astrocyte marker was also strongly attenuated in Tac4-/- mice. Analysis of TG samples with a mouse neuroinflammation panel of 770 genes revealed that regulation of microglia and cytotoxic cell-related genes were significantly different in saline-treated Tac4-/- mice compared to their wild-types. It is concluded that HK-1 may participate in neuron-glia interactions both under physiological and inflammatory conditions and mediate pain in the trigeminal system.

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Section: Discussionmentioning

confidence: 97%

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Aczél

Kecskés

Kun

et al. 2020

IJMS

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“…Few studies measured the periorbital von Frey thresholds after repeated systemic NTG injections. Because of the difficulties in practice and unstable results, a decrease or no change in periorbital thresholds has been reported after NTG injection [25]. Therefore, in our study, we only measured hind paw mechanical hyperalgesia.…”

Section: Animal Model Of Chronic Migrainementioning

confidence: 99%

Microglia P2X4R-BDNF signalling contributes to central sensitization in a recurrent nitroglycerin-induced chronic migraine model

Long

Pan

et al. 2020

J Headache Pain

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Background: According to our previous study, microglia P2X4 receptors (P2X4Rs) play a pivotal role in the central sensitization of chronic migraine (CM). However, the molecular mechanism that underlies the crosstalk between microglia P2X4Rs and neurons of the trigeminal nucleus caudalis (TNC) is not fully understood. Therefore, the aim of this study is to examine the exact P2X4Rs signalling pathway in the development of central sensitization in a CM animal model. Methods: We used an animal model with recurrent intermittent administration of nitroglycerin (NTG), which closely mimics CM. NTG-induced basal mechanical and thermal hypersensitivity were evaluated using a von Frey filament test and an increasing-temperature hot plate apparatus (IITC). We detected P2X4Rs, brain-derived neurotrophic factor (BDNF) and phosphorylated p38 mitogen-activated protein kinase (p-p38-MAPK) expression profiles in the TNC. We investigated the effects of a P2X4R inhibitor (5-BDBD) and an agonist (IVM) on NTG-induced hyperalgesia and neurochemical changes as well as on the expression of p-p38-MAPK and BDNF. We also detected the effects of a tropomyosin-related kinase B (TrkB) inhibitor (ANA-12) on the CM animal model in vivo. Then, we evaluated the effect of 5-BDBD and SB203580 (a p38-MAPK inhibitors) on the release and synthesis of BDNF in BV2 microglia cells treated with 50 μM adenosine triphosphate (ATP). Results: Chronic intermittent administration of NTG resulted in chronic mechanical and thermal hyperalgesia, accompanied by the upregulation of P2X4Rs and BDNF expression. 5-BDBD or ANA-12 prevented hyperalgesia induced by NTG, which was associated with a significant inhibition of the NTG-induced increase in phosphorylated extracellular regulated protein kinases (p-ERK) and calcitonin gene related peptide (CGRP) release in the TNC. Repeated administration of IVM produced sustained hyperalgesia and significantly increased the levels of pERK and CGRP release in the TNC. Activating P2X4Rs with ATP triggered BDNF release and increased BDNF synthesis in BV2 microglia, and these results were then reduced by 5-BDBD or SB203580. Conclusions: Our results indicated that the P2X4R contributes to the central sensitization of CM by releasing BDNF and promoting TNC neuronal hyper-excitability. Blocking microglia P2X4R-BDNF signalling may have an effect on the prevention of migraine chronification.

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“…In rodents, NO donors evoke elevated CGRP blood levels, meningeal inflammation, photo and phonophobia, sensitization of central neurons of the trigeminal nucleus caudalis (TNC), cephalic and extra‐cephalic allodynia, as well as spontaneous facial pain. The effectiveness of clinically relevant treatments like sumatriptan, CGRP antagonists and antibodies, anti‐inflammatory drugs, or prophylactic drugs like propranolol and topiramate further support the relevance of these animal models of migraine (Bates et al ., ; Jansen‐Olesen et al ., ; Pradhan et al ., ; Farkas et al ., ; Goadsby et al ., ; Harris et al ., ; Schytz et al ., ). Effects of systemic ISDN injections were recently described in rats, with a facilitation of C‐fibre‐evoked responses in 50% of second‐order central neurons (Flores Ramos et al ., ; Dallel et al ., ), leading to cutaneous pain sensitization.…”

Section: Introductionmentioning

confidence: 97%

Effects of systemic inhibitors of acid‐sensing ion channels 1 (ASIC1) against acute and chronic mechanical allodynia in a rodent model of migraine

Verkest

Piquet

Diochot

et al. 2018

British J Pharmacology

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Utility of different outcome measures for the nitroglycerin model of migraine in mice

Cited by 45 publications

References 67 publications

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization

Microglia P2X4R-BDNF signalling contributes to central sensitization in a recurrent nitroglycerin-induced chronic migraine model

Effects of systemic inhibitors of acid‐sensing ion channels 1 (ASIC1) against acute and chronic mechanical allodynia in a rodent model of migraine

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