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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 ameliorates mechanical allodynia in a trigeminal neuralgia rat model. Rats administered Res only on day 14 (a) or on days 14, 15, 16, 17, and 18 (b) post-CCI showed a significant increase in mechanical withdrawal compared with that of the control group. a Resveratrol (100, 200, and 400 μg/ml) orally single administrated at day 14 ameliorated pain-related behaviors in a dose-dependent manner, and this effect lasted for more than 24 h. b Consecutive administration of resveratrol at postoperative days 14, 15, 16, 17, and 18 reversed the mechanical allodynia in the CCI rats. c The AMPK inhibitor compound C reversed the effects of Res on CCI-induced mechanical allodynia. Drug administration is indicated by the arrows (n = 8 each group). Two-way ANOVA revealed a significant difference at *P < 0.05 and **P < 0.01 versus control; #P < 0.05 and ##P < 0.01 versus the CCI group; and &P < 0.05 and &&P < 0.01 versus the CCI + Res 400 mg/kg group
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Fig1: Resveratrol ameliorates mechanical allodynia in a trigeminal neuralgia rat model. Rats administered Res only on day 14 (a) or on days 14, 15, 16, 17, and 18 (b) post-CCI showed a significant increase in mechanical withdrawal compared with that of the control group. a Resveratrol (100, 200, and 400 μg/ml) orally single administrated at day 14 ameliorated pain-related behaviors in a dose-dependent manner, and this effect lasted for more than 24 h. b Consecutive administration of resveratrol at postoperative days 14, 15, 16, 17, and 18 reversed the mechanical allodynia in the CCI rats. c The AMPK inhibitor compound C reversed the effects of Res on CCI-induced mechanical allodynia. Drug administration is indicated by the arrows (n = 8 each group). Two-way ANOVA revealed a significant difference at *P < 0.05 and **P < 0.01 versus control; #P < 0.05 and ##P < 0.01 versus the CCI group; and &P < 0.05 and &&P < 0.01 versus the CCI + Res 400 mg/kg group

Mentions: In this study, rats that received CCI of the trigeminal nerve exhibited mechanical allodynia (Fig. 1). There were no significant differences in pain-related behaviors between the control group and the other groups before surgery. A marked decrease in mechanical withdrawal was observed 7 days after CCI and followed by a peak on day 14. Thus, resveratrol was administered to the CCI rats on day 14. These pain-related behaviors were greatly ameliorated by resveratrol (100, 200, and 400 μg/ml) orally single administrated at postoperative 14 days in a dose-dependent manner, and the effect lasted for more than 24 h (Fig. 1a). However, the effects of resveratrol were abolished by the AMPK inhibitor compound C (Fig. 1c). In addition, consecutive administration of resveratrol at postoperative days 14, 15, 16, 17, and 18 reversed the mechanical allodynia in the CCI rats (Fig. 1b). These results suggest that AMPK activation via resveratrol had a clearly positive effect on mechanic analgesia in the CCI rats.Fig. 1


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 ameliorates mechanical allodynia in a trigeminal neuralgia rat model. Rats administered Res only on day 14 (a) or on days 14, 15, 16, 17, and 18 (b) post-CCI showed a significant increase in mechanical withdrawal compared with that of the control group. a Resveratrol (100, 200, and 400 μg/ml) orally single administrated at day 14 ameliorated pain-related behaviors in a dose-dependent manner, and this effect lasted for more than 24 h. b Consecutive administration of resveratrol at postoperative days 14, 15, 16, 17, and 18 reversed the mechanical allodynia in the CCI rats. c The AMPK inhibitor compound C reversed the effects of Res on CCI-induced mechanical allodynia. Drug administration is indicated by the arrows (n = 8 each group). Two-way ANOVA revealed a significant difference at *P < 0.05 and **P < 0.01 versus control; #P < 0.05 and ##P < 0.01 versus the CCI group; and &P < 0.05 and &&P < 0.01 versus the CCI + Res 400 mg/kg group
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Resveratrol ameliorates mechanical allodynia in a trigeminal neuralgia rat model. Rats administered Res only on day 14 (a) or on days 14, 15, 16, 17, and 18 (b) post-CCI showed a significant increase in mechanical withdrawal compared with that of the control group. a Resveratrol (100, 200, and 400 μg/ml) orally single administrated at day 14 ameliorated pain-related behaviors in a dose-dependent manner, and this effect lasted for more than 24 h. b Consecutive administration of resveratrol at postoperative days 14, 15, 16, 17, and 18 reversed the mechanical allodynia in the CCI rats. c The AMPK inhibitor compound C reversed the effects of Res on CCI-induced mechanical allodynia. Drug administration is indicated by the arrows (n = 8 each group). Two-way ANOVA revealed a significant difference at *P < 0.05 and **P < 0.01 versus control; #P < 0.05 and ##P < 0.01 versus the CCI group; and &P < 0.05 and &&P < 0.01 versus the CCI + Res 400 mg/kg group
Mentions: In this study, rats that received CCI of the trigeminal nerve exhibited mechanical allodynia (Fig. 1). There were no significant differences in pain-related behaviors between the control group and the other groups before surgery. A marked decrease in mechanical withdrawal was observed 7 days after CCI and followed by a peak on day 14. Thus, resveratrol was administered to the CCI rats on day 14. These pain-related behaviors were greatly ameliorated by resveratrol (100, 200, and 400 μg/ml) orally single administrated at postoperative 14 days in a dose-dependent manner, and the effect lasted for more than 24 h (Fig. 1a). However, the effects of resveratrol were abolished by the AMPK inhibitor compound C (Fig. 1c). In addition, consecutive administration of resveratrol at postoperative days 14, 15, 16, 17, and 18 reversed the mechanical allodynia in the CCI rats (Fig. 1b). These results suggest that AMPK activation via resveratrol had a clearly positive effect on mechanic analgesia in the CCI rats.Fig. 1

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