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Resveratrol suppresses glial activation and alleviates trigeminal neuralgia via activation of AMPK.

Yang YJ, Hu L, Xia YP, Jiang CY, Miao C, Yang CQ, Yuan M, Wang L - J Neuroinflammation (2016)

Bottom Line: We found that resveratrol significantly attenuated trigeminal allodynia dose-dependently and decreased the increased expression of CGRP and c-Fos in the STN.Additionally, resveratrol showed an inhibitory effect on CCI-evoked astrocyte and microglia activation and reduced production of pro-inflammatory cytokines in the STN.Furthermore, the antinociceptive effect of resveratrol was partially mediated by reduced phosphorylation of MAP kinases via adenosine monophosphate-activated protein kinase (AMPK) activation.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, People's Republic of China. yangyanjing@njmu.edu.cn.

ABSTRACT

Background: Glial activation and neuroinflammation in the spinal trigeminal nucleus (STN) play a pivotal role in the genesis and maintenance of trigeminal neuralgia (TN). Resveratrol, a natural compound from grape and red wine, has a potential anti-inflammatory effect. We hypothesized that resveratrol could significantly suppress neuroinflammation in the STN mediated by glial activation and further relieve TN. In this study, we evaluated whether resveratrol could alleviate trigeminal allodynia and explore the mechanism underlying the antinociceptive effect of resveratrol.

Methods: Animals were orally injected with resveratrol after chronic constriction injury (CCI) of the infraorbital nerve. Mechanical thresholds of the affected whisker pad were measured to assess nociceptive behaviors. The STN was harvested to quantify the changing levels of p-NR1, p-PKC, TNF-α, and IL1-β by western blotting and detect the expression of calcitonin gene-related peptide (CGRP) and c-Fos by immunofluorescence. Glial activation was observed by immunofluorescence and western blotting. Mitogen-activated protein kinase (MAPK) phosphorylation in vivo and in vitro was examined by western blotting.

Results: We found that resveratrol significantly attenuated trigeminal allodynia dose-dependently and decreased the increased expression of CGRP and c-Fos in the STN. Additionally, resveratrol showed an inhibitory effect on CCI-evoked astrocyte and microglia activation and reduced production of pro-inflammatory cytokines in the STN. Furthermore, the antinociceptive effect of resveratrol was partially mediated by reduced phosphorylation of MAP kinases via adenosine monophosphate-activated protein kinase (AMPK) activation.

Conclusions: AMPK activation in the STN glia via resveratrol has utility in the treatment of CCI-induced neuroinflammation and further implicates AMPK as a novel target for the attenuation of trigeminal neuralgia.

No MeSH data available.


Related in: MedlinePlus

Resveratrol inhibits phosphorylation of c-Fos and CGRP in the STN. Immunofluorescence analysis data show CGRP expression and c-Fos-immunoreactive neuron number. The CGRP and c-Fos level was significantly increased by CCI, and resveratrol suppressed the increase of CGRP expression (a) and attenuated the increase of c-Fos-immunoreactive neuron number (b). Resveratrol alone had no effect on CGRP expression and c-Fos-immunoreactive neuron number. n = 5, five images per animal. *P < 0.05 and **P < 0.01 versus control; and #P < 0.05 and ##P < 0.01 versus the CCI group
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Fig2: Resveratrol inhibits phosphorylation of c-Fos and CGRP in the STN. Immunofluorescence analysis data show CGRP expression and c-Fos-immunoreactive neuron number. The CGRP and c-Fos level was significantly increased by CCI, and resveratrol suppressed the increase of CGRP expression (a) and attenuated the increase of c-Fos-immunoreactive neuron number (b). Resveratrol alone had no effect on CGRP expression and c-Fos-immunoreactive neuron number. n = 5, five images per animal. *P < 0.05 and **P < 0.01 versus control; and #P < 0.05 and ##P < 0.01 versus the CCI group

Mentions: CGRP has an essential role in trigeminal nociceptive processing. As shown in Fig. 2a, significantly higher CGRP level was induced by CCI than that in the control group. Treatment with resveratrol suppressed the increase of the CGRP level. Resveratrol alone had no effect on the expression of CGRP. Furthermore, CCI remarkably increased the number of c-Fos-immunoreactive neurons in the spinal trigeminal nucleus (STN), and the increase of positive neurons was significantly attenuated by administration of resveratrol. Similarly, resveratrol alone did not influence the number of c-Fos-immunoreactive neurons in the STN in normal rats (Fig. 2b).Fig. 2


Resveratrol suppresses glial activation and alleviates trigeminal neuralgia via activation of AMPK.

Yang YJ, Hu L, Xia YP, Jiang CY, Miao C, Yang CQ, Yuan M, Wang L - J Neuroinflammation (2016)

Resveratrol inhibits phosphorylation of c-Fos and CGRP in the STN. Immunofluorescence analysis data show CGRP expression and c-Fos-immunoreactive neuron number. The CGRP and c-Fos level was significantly increased by CCI, and resveratrol suppressed the increase of CGRP expression (a) and attenuated the increase of c-Fos-immunoreactive neuron number (b). Resveratrol alone had no effect on CGRP expression and c-Fos-immunoreactive neuron number. n = 5, five images per animal. *P < 0.05 and **P < 0.01 versus control; and #P < 0.05 and ##P < 0.01 versus the CCI group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4837542&req=5

Fig2: Resveratrol inhibits phosphorylation of c-Fos and CGRP in the STN. Immunofluorescence analysis data show CGRP expression and c-Fos-immunoreactive neuron number. The CGRP and c-Fos level was significantly increased by CCI, and resveratrol suppressed the increase of CGRP expression (a) and attenuated the increase of c-Fos-immunoreactive neuron number (b). Resveratrol alone had no effect on CGRP expression and c-Fos-immunoreactive neuron number. n = 5, five images per animal. *P < 0.05 and **P < 0.01 versus control; and #P < 0.05 and ##P < 0.01 versus the CCI group
Mentions: CGRP has an essential role in trigeminal nociceptive processing. As shown in Fig. 2a, significantly higher CGRP level was induced by CCI than that in the control group. Treatment with resveratrol suppressed the increase of the CGRP level. Resveratrol alone had no effect on the expression of CGRP. Furthermore, CCI remarkably increased the number of c-Fos-immunoreactive neurons in the spinal trigeminal nucleus (STN), and the increase of positive neurons was significantly attenuated by administration of resveratrol. Similarly, resveratrol alone did not influence the number of c-Fos-immunoreactive neurons in the STN in normal rats (Fig. 2b).Fig. 2

Bottom Line: We found that resveratrol significantly attenuated trigeminal allodynia dose-dependently and decreased the increased expression of CGRP and c-Fos in the STN.Additionally, resveratrol showed an inhibitory effect on CCI-evoked astrocyte and microglia activation and reduced production of pro-inflammatory cytokines in the STN.Furthermore, the antinociceptive effect of resveratrol was partially mediated by reduced phosphorylation of MAP kinases via adenosine monophosphate-activated protein kinase (AMPK) activation.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Key Laboratory of Oral Disease, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu, 210029, People's Republic of China. yangyanjing@njmu.edu.cn.

ABSTRACT

Background: Glial activation and neuroinflammation in the spinal trigeminal nucleus (STN) play a pivotal role in the genesis and maintenance of trigeminal neuralgia (TN). Resveratrol, a natural compound from grape and red wine, has a potential anti-inflammatory effect. We hypothesized that resveratrol could significantly suppress neuroinflammation in the STN mediated by glial activation and further relieve TN. In this study, we evaluated whether resveratrol could alleviate trigeminal allodynia and explore the mechanism underlying the antinociceptive effect of resveratrol.

Methods: Animals were orally injected with resveratrol after chronic constriction injury (CCI) of the infraorbital nerve. Mechanical thresholds of the affected whisker pad were measured to assess nociceptive behaviors. The STN was harvested to quantify the changing levels of p-NR1, p-PKC, TNF-α, and IL1-β by western blotting and detect the expression of calcitonin gene-related peptide (CGRP) and c-Fos by immunofluorescence. Glial activation was observed by immunofluorescence and western blotting. Mitogen-activated protein kinase (MAPK) phosphorylation in vivo and in vitro was examined by western blotting.

Results: We found that resveratrol significantly attenuated trigeminal allodynia dose-dependently and decreased the increased expression of CGRP and c-Fos in the STN. Additionally, resveratrol showed an inhibitory effect on CCI-evoked astrocyte and microglia activation and reduced production of pro-inflammatory cytokines in the STN. Furthermore, the antinociceptive effect of resveratrol was partially mediated by reduced phosphorylation of MAP kinases via adenosine monophosphate-activated protein kinase (AMPK) activation.

Conclusions: AMPK activation in the STN glia via resveratrol has utility in the treatment of CCI-induced neuroinflammation and further implicates AMPK as a novel target for the attenuation of trigeminal neuralgia.

No MeSH data available.


Related in: MedlinePlus