PMID- 25889689 OWN - NLM STAT- MEDLINE DCOM- 20160810 LR - 20191210 IS - 1742-2094 (Electronic) IS - 1742-2094 (Linking) VI - 12 DP - 2015 Mar 25 TI - Inhibition of the spinal astrocytic JNK/MCP-1 pathway activation correlates with the analgesic effects of tanshinone IIA sulfonate in neuropathic pain. PG - 57 LID - 10.1186/s12974-015-0279-7 [doi] LID - 57 AB - BACKGROUND: Neuropathic pain (NP) continues to be challenging to treat due to lack of effective drugs. Accumulating evidence elucidated that glia-mediated inflammatory reactions play a pivotal role in the introduction and development of NP. Besides, activation of the c-Jun N-terminal kinase (JNK)/monocyte chemoattractant protein-1 (MCP-1) pathway in astrocytes has been reported to be critical for spinal astrocytic activation and neuropathic pain development after spinal nerve ligation (SNL). Tanshinone IIA, a major active component of a traditional Chinese drug, Danshen, possesses potent immuno-suppressive activities. The present study was undertaken to assess whether intraperitoneal administration of tanshinone IIA sulfonate (TIIAS) has analgesic effect on SNL-induced neuropathic pain and whether the inhibition of astrocytic activation and JNK/MCP-1 pathway is involved in the analgesic effect of TIIAS. METHODS: The effects of TIIAS on SNL-induced mechanical allodynia were assessed by behavioral testing. Immunofluorescence histochemical staining was used to detect changes of spinal astrocytes and spinal pJNK expression and localization. Immunofluorescence histochemistry and Western blot analysis were used to quantify the SNL-induced spinal pJNK expression after TIIAS administration. Enzyme-linked immunosorbent assay (ELISA) was used to detect the SNL-induced spinal expression of pro-inflammatory cytokines and MCP-1. RESULTS: Our results indicated that intraperitoneal TIIAS up-regulated the mechanical paw withdrawal threshold (PWT) of NP, while astrocytic activation was suppressed and accompanied by the down-regulation of IL-1beta and TNF-alpha expression, as well as JNK phosphorylation in the spinal dorsal horn. Additionally, the release of MCP-1 was dose dependently decreased. After co-treatment with TIIAS and JNK inhibitor (SP600125), no significant increases in mechanical PWT and MCP-1 expression were observed compared with the TIIAS-treated group. CONCLUSIONS: The present results suggest that the analgesic effects of TIIAS in neuropathic pain are mainly mediated by the down-regulation of SNL-induced astrocytic activation, which is via the inhibition of JNK/MCP-1 pathway. FAU - Tang, Jun AU - Tang J AD - Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China. fmmutangjun@qq.com. AD - Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, People's Republic of China. fmmutangjun@qq.com. FAU - Zhu, Chao AU - Zhu C AD - Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, No. 15 West Changle Road, Xi'an, 710032, People's Republic of China. zhuchaode@gmail.com. FAU - Li, Zhi-hong AU - Li ZH AD - Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, No. 1 Xinsi Road, Xi'an, 710038, People's Republic of China. tdlizhihong@163.com. FAU - Liu, Xiao-yu AU - Liu XY AD - Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China. nzliuxiaoyu@163.com. FAU - Sun, Shu-kai AU - Sun SK AD - Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169 West Changle Road, Xi'an, 710032, People's Republic of China. kqsunshukai@163.com. FAU - Zhang, Ting AU - Zhang T AD - Department of Anatomy, Histology and Embryology, K. K. Leung Brain Research Centre, The Fourth Military Medical University, No. 169 West Changle Road, Xi'an, 710032, People's Republic of China. jpzhangting@163.com. FAU - Luo, Zhuo-jing AU - Luo ZJ AD - Institute of Orthopaedics, Xijing Hospital, The Fourth Military Medical University, No. 15 West Changle Road, Xi'an, 710032, People's Republic of China. zjluo@fmmu.edu.cn. FAU - Zhang, Hui AU - Zhang H AD - Department of Anesthesiology, School of Stomatology, The Fourth Military Medical University, No. 145 West Changle Road, Xi'an, 710032, People's Republic of China. kouqiangzhanghui@163.com. FAU - Li, Wei-yan AU - Li WY AD - Department of Anesthesiology, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, People's Republic of China. nzliweiyan@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150325 PL - England TA - J Neuroinflammation JT - Journal of neuroinflammation JID - 101222974 RN - 0 (Abietanes) RN - 0 (Analgesics) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 03UUH3J385 (tanshinone) SB - IM MH - Abietanes/*therapeutic use MH - Analgesics/*therapeutic use MH - Analysis of Variance MH - Animals MH - Chemokine CCL2/*metabolism MH - Disease Models, Animal MH - Dose-Response Relationship, Drug MH - Hyperalgesia/drug therapy/etiology MH - MAP Kinase Signaling System/*drug effects MH - Male MH - Movement Disorders/etiology MH - Neuralgia/complications/*drug therapy/pathology MH - Pain Threshold/drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Spinal Cord/drug effects/*metabolism MH - Spinal Nerves/injuries PMC - PMC4406216 EDAT- 2015/04/19 06:00 MHDA- 2016/08/11 06:00 PMCR- 2015/03/25 CRDT- 2015/04/19 06:00 PHST- 2015/01/19 00:00 [received] PHST- 2015/03/05 00:00 [accepted] PHST- 2015/04/19 06:00 [entrez] PHST- 2015/04/19 06:00 [pubmed] PHST- 2016/08/11 06:00 [medline] PHST- 2015/03/25 00:00 [pmc-release] AID - 10.1186/s12974-015-0279-7 [pii] AID - 279 [pii] AID - 10.1186/s12974-015-0279-7 [doi] PST - epublish SO - J Neuroinflammation. 2015 Mar 25;12:57. doi: 10.1186/s12974-015-0279-7.