Pregabalin alleviates the nitroglycerin-induced hyperalgesia in rats

Di, Wei; Zheng, Zhaomin; Xiao, Zheman; Qi, Wang; Shi, Xianbo; Luo, N.; Lin, Jie; Ding, Mingxing; Zhang, A.-W.; Fang, Yun

doi:10.1016/j.neuroscience.2014.08.056

Cited by 13 publications

(8 citation statements)

References 38 publications

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“…β-actin and Histone H3 were used as internal reference proteins for different molecules. Concentrations of protein samples were determined using the BCA method and western blotting was performed as described previously with some modification [ 10 ]: 40 μg protein in 20 μL volume was subjected to 10 % sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). After transferring the proteins onto polyvinylidene difluoride (PVDF) membranes, the membranes were washed with TTBS for 5 min and then incubated with skim milk powder solution for 1 h. Primary antibody against c-Fos (1:500), IκBα (1:500), p-IκBα (1:500), and nuclear NF-кB subunit p65 (1:400), β-actin (1:1000) or Histone H3 (1:500) was added and the membranes were incubated at 4 °C overnight.…”

Section: Methodsmentioning

confidence: 99%

“…Upon stimulation, IκBα is degraded and free NF-κB subunits to enter the nucleus and subsequently cause the expression of inflammatory genes which are the main regulatory enzymes for NO [ 9 ]. Thus, some therapies targeting these relevant pathways have been widely investigated regarding their potential to attenuate the damage caused by migraine [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

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Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-кB

Zhang

et al. 2016

J Headache Pain

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BackgroundAs a complex nervous system disease, migraine causes severe healthy and social issues worldwide. Valproate (VPA) is a widely used treatment agent against seizures and bipolar disorder, and its function to alleviate damage due to migraine has also been verified in clinical investigations. However, the mechanism underlying the protective effect of VPA against migraine remains poorly revealed. In the current study, the major purpose was to uncover the mechanism which drove VPA to antagonize migraine.MethodsNitroglycerin (NTG) was employed to induce a migraine model in rats and the migraine animals were exposed to treatment of VPA of different doses. Thereafter, the levels of indicators related to oxidative stress were measured and used to evaluate the anti-oxidant potential of VPA. The expression of calcitonin gene-related peptide (CGRP) and c-Fos was also quantified with ELISA and immunohistochemistry, respectively. Western blotting and electrophoretic mobility shift assays (EMSA) were conducted to explore the effect of VPA treatment on NF-кB pathway.ResultsNTG induced the activation of oxidative stress and led to migraine in model animals, but pre-treatment with VPA attenuated the damage due to migraine attack in brain tissues. The level of lipid peroxidation was significantly reduced while the prodcution of anti-oxidant factors was restored. Furthermore, expressions of CGRP and c-Fos, which represented the neuronal activation, were also down-regulated by VPA. The results of western blotting and EMSA demonstrated that the above mentioned effect of VPA acted through the inhibition of NF-кB pathway.ConclusionsAlthough controversies on the effect of VPA on NF-кB pathway existed, our study revealed an alternative mechanism of VPA in protecting against migraine, which would promote the development of therapeutic strategies of migraine.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-кB

Zhang

et al. 2016

J Headache Pain

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“…One possibility is that decreased neuronal cytoarchitecture is driven through a CGRP related mechanism and direct antagonism of the CGRP receptor reverses these alterations. NTG treatment was previously found to upregulate CGRP in the blood, TNC, and dura mater demonstrating a direct link between NTG and CGRP [75][76][77] . Future studies will explore the relationship between CGRP and other migraine therapies with neuronal cytoarchitecture.…”

Section: Discussionmentioning

confidence: 86%

Neuronal complexity is attenuated in chronic migraine and restored by HDAC6 inhibition

Bertels

Grewal

Dripps

et al. 2020

Preprint

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Migraine is the third most prevalent disease worldwide and current therapies provide only partial relief. Greater insight into molecular migraine mechanisms would create novel therapies. Cytoskeletal flexibility is fundamental to neuronal-plasticity and is dependent on microtubule dynamicity. Histone-deacetylase-6 (HDAC6) decreases microtubule dynamics by deacetylating its primary substrate, α-tubulin. We use validated models of chronic migraine to show that HDAC6-inhibition is an effective migraine treatment and reveal an undiscovered cytoarchitectural basis for migraine chronicity. The human migraine trigger, nitroglycerin, produced chronic migraine-associated pain and decreased neurite growth in pain-processing regions, and these were reversed by HDAC6 inhibition.Cortical spreading depression (CSD), a physiological correlate of migraine aura, also caused decreased cortical neurite growth, while administration of HDAC6-inhibitor restored neuronal complexity and decreased CSD. Our results demonstrate that disruptions in neuronal cytoarchitecture are a feature of chronic migraine, and evolving migraine therapies might include agents that restore microtubule stability and neuronal plasticity.

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“…Additionally, CGRP can induce headache (56), while CGRP receptor antagonists can abort migraine (57); thus, CGRP is an active target for migraine drug development (58). In preclinical models, NTG treatment results in increased levels of CGRP in the blood (59), TNC, and dura mater (27,46). In addition, in another rodent model of headache, the number of CGRP-expressing TGs increased in correspondence with increased pain (60).…”

Section: Discussionmentioning

confidence: 99%

Soluble guanylyl cyclase is a critical regulator of migraine-associated pain

et al. 2017

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Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology. Soluble guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim of this study was to identify the precise role of sGC in acute and chronic migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL-102), and tested its hyperalgesic properties in mice. We also determined the effect of VL-102 on c-fos and calcitonin gene related peptide (CGRP) immunoreactivity within the trigeminovascular complex. In addition, we also tested the known sGC inhibitor, ODQ, within the chronic nitroglycerin migraine model. Results VL-102-evoked acute and chronic mechanical cephalic and hind-paw allodynia in a dose-dependent manner, which was blocked by the migraine medications sumatriptan, propranolol, and topiramate. In addition, VL-102 also increased c-fos and CGRP expressing cells within the trigeminovascular complex. Importantly, ODQ completely inhibited acute and chronic hyperalgesia induced by nitroglycerin. ODQ also blocked hyperalgesia already established by chronic nitroglycerin, implicating this pathway in migraine chronicity. Conclusions These results indicate that nitroglycerin causes migraine-related pain through stimulation of the sGC pathway, and that super-activation of this receptor may be an important component for the maintenance of chronic migraine. This work opens the possibility for negative sGC modulators as novel migraine therapies.

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Pregabalin alleviates the nitroglycerin-induced hyperalgesia in rats

Cited by 13 publications

References 38 publications

Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-кB

Valproate ameliorates nitroglycerin-induced migraine in trigeminal nucleus caudalis in rats through inhibition of NF-кB

Neuronal complexity is attenuated in chronic migraine and restored by HDAC6 inhibition

Soluble guanylyl cyclase is a critical regulator of migraine-associated pain

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