PMID- 28306606 OWN - NLM STAT- MEDLINE DCOM- 20180110 LR - 20180110 IS - 1473-558X (Electronic) IS - 0959-4965 (Linking) VI - 28 IP - 6 DP - 2017 Apr 12 TI - Spinal microglial P2X4 receptor-brain-derived neurotrophic factor signaling regulates nicotine withdrawal-induced hyperalgesia. PG - 339-347 LID - 10.1097/WNR.0000000000000769 [doi] AB - Nicotine withdrawal (NTW) has been shown to increase pain sensitivity. However, the pathogenesis of NTW-induced hyperalgesia syndrome is unknown. Microglial activation, with increased expression of the P2X4 receptor (P2X4R) and brain-derived neurotrophic factor (BDNF) as important markers, is associated with hyperalgesia; therefore, these markers may represent an unprecedented target to prevent hyperalgesia. In this study, we explored the contributions of spinal microglial P2X4R-BDNF signaling in NTW-induced hyperalgesia. Immunohistochemical analysis showed that spinal microglia were activated and that the P2X4R level was increased and colocalized with ionized calcium-binding adapter molecule 1 in NTW-induced hyperalgesia. Furthermore, we showed that microglial activation with NTW resulted in an increased expression of spinal P2X4R and an elevated release of BDNF. Intrathecal minocycline (a specific inhibitor of microglial activation) reversed thermal hyperalgesia as well as increased the spinal microglial P2X4R and BDNF levels induced by NTW. To the best of our knowledge, the present study provides evidence that spinal microglial P2X4R-BDNF signaling is critical for the development of NTW-induced hyperalgesia. FAU - Zhang, Xiaodi AU - Zhang X AD - aJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, Jiangsu Province bDepartment of Anesthesiology, Liaocheng People's Hospital, Liaocheng, Shandong cDepartment of Medicine, Hebei North University, Zhangjiakou, Hebei, China. FAU - Xu, Pengcheng AU - Xu P FAU - Li, Chengbao AU - Li C FAU - Zhu, Wenchao AU - Zhu W FAU - Wu, Shanshan AU - Wu S FAU - Yu, Ailan AU - Yu A FAU - Ding, Yonghong AU - Ding Y FAU - Wang, Qinghe AU - Wang Q FAU - Zhang, Zongwang AU - Zhang Z LA - eng PT - Journal Article PL - England TA - Neuroreport JT - Neuroreport JID - 9100935 RN - 0 (Aif1 protein, rat) RN - 0 (Analgesics, Non-Narcotic) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Calcium-Binding Proteins) RN - 0 (Microfilament Proteins) RN - 0 (Nicotinic Agonists) RN - 0 (Receptors, Purinergic P2X4) RN - 6M3C89ZY6R (Nicotine) RN - FYY3R43WGO (Minocycline) SB - IM MH - Analgesics, Non-Narcotic/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Calcium-Binding Proteins/metabolism MH - Disease Models, Animal MH - Hot Temperature MH - Hyperalgesia/chemically induced/drug therapy/*metabolism/pathology MH - Male MH - Microfilament Proteins/metabolism MH - Microglia/drug effects/*metabolism/pathology MH - Minocycline/pharmacology MH - Nicotine/toxicity MH - Nicotinic Agonists/toxicity MH - Pain Threshold/drug effects/physiology MH - Rats, Sprague-Dawley MH - Receptors, Purinergic P2X4/*metabolism MH - Spinal Cord/drug effects/*metabolism/pathology MH - Substance Withdrawal Syndrome/drug therapy/*metabolism/pathology EDAT- 2017/03/18 06:00 MHDA- 2018/01/11 06:00 CRDT- 2017/03/18 06:00 PHST- 2017/03/18 06:00 [pubmed] PHST- 2018/01/11 06:00 [medline] PHST- 2017/03/18 06:00 [entrez] AID - 10.1097/WNR.0000000000000769 [doi] PST - ppublish SO - Neuroreport. 2017 Apr 12;28(6):339-347. doi: 10.1097/WNR.0000000000000769.