PMID- 28608248 OWN - NLM STAT- MEDLINE DCOM- 20180423 LR - 20181202 IS - 1573-7365 (Electronic) IS - 0885-7490 (Linking) VI - 32 IP - 4 DP - 2017 Aug TI - The analgesic effect of trans-resveratrol is regulated by calcium channels in the hippocampus of mice. PG - 1311-1321 LID - 10.1007/s11011-017-0033-1 [doi] AB - 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 Ca(2+)/calmodulin-dependent signaling in the spinal cord of mice. The aim of this study was to explore the involvement of Ca(2+) 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, CaCl(2), ryanodine or EGTA. The effects of trans-resveratrol and the combination on Ca(2+)/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 Ca(2+), 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 CaCl(2) 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. FAU - Wang, Weijie AU - Wang W AD - Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China. FAU - Yu, Yingcong AU - Yu Y AD - Department of Gastroenterology, Wenzhou People's Hospital, Wenzhou No. 3 Clinical Institute affiliated to Wenzhou Medical University, Wenzhou, Zhejiang Province, 325000, China. FAU - Li, Jing AU - Li J AD - Department of Pharmacy, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266003, China. FAU - Wang, Lin AU - Wang L AD - Department of Clinical Pharmacy, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, 310006, China. FAU - Li, Zhi AU - Li Z AD - Department of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY, 14214, USA. AD - Department of Thyroid Gland and Breast Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China. FAU - Zhang, Chong AU - Zhang C AD - Department of Thyroid Gland and Breast Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China. FAU - Zhen, Linlin AU - Zhen L AD - Department of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY, 14214, USA. FAU - Ding, Lianshu AU - Ding L AD - Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China. FAU - Wang, Gang AU - Wang G AD - Department of Clinical Pharmacy, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, 310006, China. FAU - Sun, Xiaoyang AU - Sun X AD - Department of Neurosurgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China. xiaoyangsunhayy@163.com. FAU - Xu, Ying AU - Xu Y AD - Department of Pharmaceutical Sciences, School of Pharmacy & Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY, 14214, USA. yxu9@buffalo.edu. AD - Department of Thyroid Gland and Breast Surgery, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu Province, 223300, China. yxu9@buffalo.edu. LA - eng PT - Journal Article DEP - 20170612 PL - United States TA - Metab Brain Dis JT - Metabolic brain disease JID - 8610370 RN - 0 (Analgesics) RN - 0 (Calcium Channel Blockers) RN - 0 (Calcium Channels) RN - 0 (Calcium Chelating Agents) RN - 0 (Stilbenes) RN - 15662-33-6 (Ryanodine) RN - 526U7A2651 (Egtazic Acid) RN - 57WA9QZ5WH (Nimodipine) RN - Q369O8926L (Resveratrol) SB - IM MH - Analgesics/pharmacology/*therapeutic use MH - Animals MH - Calcium Channel Blockers/pharmacology MH - Calcium Channels/*metabolism MH - Calcium Chelating Agents/pharmacology MH - Egtazic Acid/pharmacology MH - Hippocampus/*drug effects/metabolism MH - Mice MH - Nimodipine/pharmacology MH - Pain/*drug therapy/metabolism MH - Pain Measurement MH - Pain Threshold/drug effects MH - Resveratrol MH - Ryanodine/pharmacology MH - Stilbenes/pharmacology/*therapeutic use OTO - NOTNLM OT - Antinociceptive OT - BDNF OT - CaMKII OT - Calcium channels OT - Calcium/caffeine-sensitive pools OT - Trans-resveratrol EDAT- 2017/06/14 06:00 MHDA- 2018/04/24 06:00 CRDT- 2017/06/14 06:00 PHST- 2016/09/20 00:00 [received] PHST- 2017/05/11 00:00 [accepted] PHST- 2017/06/14 06:00 [pubmed] PHST- 2018/04/24 06:00 [medline] PHST- 2017/06/14 06:00 [entrez] AID - 10.1007/s11011-017-0033-1 [pii] AID - 10.1007/s11011-017-0033-1 [doi] PST - ppublish SO - Metab Brain Dis. 2017 Aug;32(4):1311-1321. doi: 10.1007/s11011-017-0033-1. Epub 2017 Jun 12.