title: Resveratrol-induced antinociception is involved in calcium channels and calcium/caffeine-sensitive pools.
abstract: 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.
authors.affiliation: Department of Thyroid Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Neurology, Lianyungang second people's Hospital, Lianyungang, Jiangsu Province, China.
authors.forename: Jiechun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, China.
authors.forename: Weijie
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY.
authors.forename: Quan
authors.initials: Q
authors.lastname: Ma
authors.affiliation: Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Pingyang Hospital of Traditional Chinese Medicine, Pingyang, Zhejiang Province, China.
authors.forename: Lichao
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Pingyang Hospital of Traditional Chinese Medicine, Pingyang, Zhejiang Province, China.
authors.forename: Meixi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Wenzhou People's Hospital, Wenzhou, Zhejiang Province, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Thyroid Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan Province, China.
authors.forename: Ruochuan
authors.initials: R
authors.lastname: Cheng
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D065096:Calcium Chelating Agents / Q000494:pharmacology; D002122:Calcium Chloride / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D008297:Male; D008813:Mice, Inbred ICR; D059225:Nociception / Q000187:drug effects*; D059226:Nociceptive Pain / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D010766:Phosphorylation; D011930:Reaction Time / Q000187:drug effects; D000077185:Resveratrol; D012433:Ryanodine / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000700:Analgesics; D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D065096:Calcium Chelating Agents; D013267:Stilbenes; D012433:Ryanodine; D002110:Caffeine; D004533:Egtazic Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002122:Calcium Chloride; D000077185:Resveratrol
keywords: BDNF; CaMKII; antinociception; calcium channels; resveratrol