Metabolic Brain Disease

, Volume 32, Issue 4, pp 1311–1321 | Cite as

The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice

  • Weijie Wang
  • Yingcong Yu
  • Jing Li
  • Lin Wang
  • Zhi Li
  • Chong Zhang
  • Linlin Zhen
  • Lianshu Ding
  • Gang Wang
  • Xiaoyang SunEmail author
  • Ying XuEmail author
Original Article


Resveratrol has been widely studied in terms of it’s potential to slow the progression of many diseases. But little is known about the mechanism of action in neuropathic pain. Neuropathic pain is the main type of chronic pain associated with tissue injury. Calcium channels and calcium/caffeine-sensitive pools are associated with analgesic pathway involving neuropathic pain. Our previous study suggested that the antinociceptive effect of resveratrol was involved in Ca2+/calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca2+ in analgesic effects of trans-resveratrol in neuropathic pain and signal pathway in hippocampus. Hot plate test was used to assess antinociceptive response when mice were treated with trans-resveratrol alone or in combination with Mk 801, nimodipine, CaCl2, ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca2+/calmodulin-dependent protein kinase II (CaMKII) and BDNF (brain-derived neurotrophic factor) expression in hippocampus were also investigated. The results showed that trans-resveratrol increased paw withdraw latency in the hot plate test. The effect of resveratrol was enhanced by Mk 801 and nimodipine. Central administration of Ca2+, however, abolished the antinociceptive effects of resveratrol. In contrast, centrally administered EGTA or ryanodine improved trans-resveratrol induced antinociception. There was a significant increase in p-CaMKII and BDNF expression in the hippocampus when resveratrol were combined with Mk 801, nimodipine, ryanodine and EGTA. Administration of CaCl2 blocked changes in p-CaMKII and BDNF levels in the hippocampus. These findings suggest that trans-resveratrol exerts the effects of antinociception through regulation of calcium channels and calcium/caffeine-sensitive pools.


Trans-resveratrol Antinociceptive Calcium channels Calcium/caffeine-sensitive pools CaMKII BDNF 



This project was supported by the Natural Science Foundation of Zhejiang Province(NO.LY15H090003)and the Public Applied Research of Zhejiang Province(NO.2016F82SA100042)to Dr. G. Wang. This work was also supported by the National Natural Science Foundation for the Youth (NSFY 81400600) and Zhejiang province key science and technology innovation team (2013TD13) to Dr. YC Yu. The authors do not have financial or personal conflicts of interest associated with this work.


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Weijie Wang
    • 1
  • Yingcong Yu
    • 2
  • Jing Li
    • 3
  • Lin Wang
    • 4
  • Zhi Li
    • 5
    • 6
  • Chong Zhang
    • 6
  • Linlin Zhen
    • 5
  • Lianshu Ding
    • 1
  • Gang Wang
    • 4
  • Xiaoyang Sun
    • 1
    Email author
  • Ying Xu
    • 5
    • 6
    Email author
  1. 1.Department of Neurosurgery, Huai’an First People’s HospitalNanjing Medical UniversityHuai’anChina
  2. 2.Department of Gastroenterology, Wenzhou People’s HospitalWenzhou No. 3 Clinical Institute affiliated to Wenzhou Medical UniversityWenzhouChina
  3. 3.Department of PharmacyThe Affiliated Hospital of Qingdao UniversityQingdaoChina
  4. 4.Department of Clinical Pharmacy, Hangzhou First People’s HospitalNanjing Medical UniversityHangzhouChina
  5. 5.Department of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical SciencesThe State University of New York at BuffaloBuffaloUSA
  6. 6.Department of Thyroid Gland and Breast Surgery, Huai’an First People’s HospitalNanjing Medical UniversityHuai’anChina

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