Resveratrol-induced antinociception is involved in calcium channels and calcium/caffeine-sensitive pools
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Xiaoyu Pan1,*, Jiechun Chen2,*, Weijie Wang3,*, Ling Chen4, Lin Wang4, Quan Ma5, Jianbo Zhang6, Lichao Chen7, Gang Wang4, Meixi Zhang7,#, Hao Wu8,#, Ruochuan Cheng1,#
1Department of Thyroid Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China
2Department of Neurology, Lianyungang second people’s Hospital, Lianyungang, Jiangsu Province, China
3Department of Neurosurgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu Province, China
4Department of Clinical Pharmacy, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China
5Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY
6Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China
7Pingyang Hospital of Traditional Chinese Medicine, Pingyang, Zhejiang Province, China
8Department of Neurology, Wenzhou People’s Hospital, Wenzhou, Zhejiang Province, China
*These authors contributed equally to this work
#These authors jointly directed this work
Ruochuan Cheng, email: [email protected]
Keywords: resveratrol, calcium channels, antinociception, CaMKII, BDNF
Received: July 22, 2016 Accepted: December 15, 2016 Published: December 22, 2016
Resveratrol has been widely investigated for its potential health properties, although little is known about its mechanism in vivo. Previous studies have indicated that resveratrol produces antinociceptive effects in mice. Calcium channels and calcium/caffeine-sensitive pools are reported to be associated with analgesic effect. The present study was to explore the involvement of Ca2+ channel and calcium/caffeine-sensitive pools in the antinociceptive response of resveratrol. Tail-flick test was used to assess antinociception in mice treated with resveratrol or the combinations of resveratrol with MK 801, nimodipine, CaCl2, ryanodine and ethylene glycol tetraacetic acid (EGTA), respectively. The Ca2+/calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) levels in the spinal cord were also investigated when treated with the above drugs. The results showed that resveratrol increased the tail flick latency in the tail-flick test, in dose-dependent manner. N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK 801 potentiated the antinociceptive effects of sub-threshold dose of resveratrol at 10 mg/kg. Ca2+ channel blocker, however, abolished the antinociceptive effects of resveratrol. In contrast to these results, EGTA or ryanodine treatment (i.c.v.) potentiated resveratrol-induced antinociception. There was a significant decrease in p-CaMKII and an increase in BDNF expression in the spinal cord when combined with MK 801, nimodipine, ryanodine and EGTA. While an increase in p-CaMKII level and a decrease in BDNF expression were observed when high dose of resveratrol combined with CaCl2. These findings suggest that resveratrol exhibits the antinociceptive effects by inhibition of calcium channels and calcium/caffeine-sensitive pools.
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