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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 reduces CCI-induced production of pro-inflammatory factors and phosphorylation of NR1 and PKCγ in the STN. a Resveratrol reduces the production of pro-inflammatory factors IL-1β and TNF-α. b Resveratrol inhibits the phosphorylation of NR1 and PKCγ. Representative western blot bands and a data summary (n = 4 each group) are shown. *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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Fig5: Resveratrol reduces CCI-induced production of pro-inflammatory factors and phosphorylation of NR1 and PKCγ in the STN. a Resveratrol reduces the production of pro-inflammatory factors IL-1β and TNF-α. b Resveratrol inhibits the phosphorylation of NR1 and PKCγ. Representative western blot bands and a data summary (n = 4 each group) are shown. *P < 0.05 and **P < 0.01 versus control; and #P < 0.05 and ##P < 0.01 versus the CCI group

Mentions: AMPK activation has been reported to inhibit neuroinflammation [21]. IL-1β and TNF-α are characterized pro-inflammatory cytokines that play an important role in inflammatory response by stimulating glial cells. The expression levels of IL-1β and TNF-α in the STN were examined by western blotting, showing that the levels of IL-1β and TNF-α were increased in the CCI rats compared to the control group (P < 0.01). Treatment with resveratrol (400 mg/kg, p.o.) inhibited the increased production of IL-1β and TNF-α in the STN (P < 0.01) (Fig. 5a). There were no significant differences between control and resveratrol alone.


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 reduces CCI-induced production of pro-inflammatory factors and phosphorylation of NR1 and PKCγ in the STN. a Resveratrol reduces the production of pro-inflammatory factors IL-1β and TNF-α. b Resveratrol inhibits the phosphorylation of NR1 and PKCγ. Representative western blot bands and a data summary (n = 4 each group) are shown. *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

Fig5: Resveratrol reduces CCI-induced production of pro-inflammatory factors and phosphorylation of NR1 and PKCγ in the STN. a Resveratrol reduces the production of pro-inflammatory factors IL-1β and TNF-α. b Resveratrol inhibits the phosphorylation of NR1 and PKCγ. Representative western blot bands and a data summary (n = 4 each group) are shown. *P < 0.05 and **P < 0.01 versus control; and #P < 0.05 and ##P < 0.01 versus the CCI group
Mentions: AMPK activation has been reported to inhibit neuroinflammation [21]. IL-1β and TNF-α are characterized pro-inflammatory cytokines that play an important role in inflammatory response by stimulating glial cells. The expression levels of IL-1β and TNF-α in the STN were examined by western blotting, showing that the levels of IL-1β and TNF-α were increased in the CCI rats compared to the control group (P < 0.01). Treatment with resveratrol (400 mg/kg, p.o.) inhibited the increased production of IL-1β and TNF-α in the STN (P < 0.01) (Fig. 5a). There were no significant differences between control and resveratrol alone.

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