机构：[1]Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China临床科室科研平台职能科室临床流行病与循证医学中心临床营养科儿科研究所首都医科大学附属北京儿童医院[2]Department of Surgical Oncology, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China临床科室职能科室临床流行病与循证医学中心肿瘤外科首都医科大学附属北京儿童医院[3]Department of Pathology, Peking University, Beijing, China[4]Department of Laboratory Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China医技科室职能科室检验中心临床流行病与循证医学中心首都医科大学附属北京儿童医院[5]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery,Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China临床科室职能科室耳鼻咽喉头颈外科临床流行病与循证医学中心首都医科大学附属北京儿童医院
Neonatal injury-induced exaggeration of pain hypersensitivity after adult trauma is a significant clinical challenge. However, the underlying mechanisms remain poorly understood. Growing evidence shows that spinal Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) contributes to chronic pain in adult rodents. Here we demonstrated that the phosphorylation and expression of SHP2 in synaptosomal fraction of the spinal dorsal horn are elevated in adult rats subjected to neonatal and adult incisions (nIN-IN), and the upregulation of SHP2 is highly correlated with pain hypersensitivity. Intrathecal blockade of SHP2 phosphorylation using a SHP2 protein tyrosine phosphatase inhibitor NSC-87877, or knockdown of SHP2 by intrathecal delivery of small interfering RNA (siRNA), ameliorates mechanical allodynia and heat hyperalgesia in nIN-IN rats. Moreover, the expression of phosphatidylinositol 3-kinase (PI3K) in the spinal dorsal horn is significantly increased in nIN-IN rats. Intrathecal application of PI3K inhibitor, LY294002 or wortmannin, alleviates pain hypersensitivity in nIN-IN rats. Additionally, intrathecal administration of NSC-87877 or SHP2 siRNA attenuates the upregulation of PI3K. Finally, no alternation of SHP2 phosphorylation in the dorsal root ganglion and dorsal root of nIN-IN rats as well as PI3K expression in the dorsal root of nIN-IN rats intrathecally treated with NSC-87877 or SHP2 siRNA is observed. These results suggest that the phosphorylation and expression of SHP2 in the spinal dorsal horn play vital roles in neonatal incision-induced exaggeration of adult incisional pain via PI3K. Thus, SHP2 and PI3K may serve as potential therapeutic targets for exaggerated incisional pain induced by neonatal and adult injuries. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
基金：
National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81500942]; BeiJing Talents Fund [2015000021469G204]
第一作者机构：[1]Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
通讯作者：
通讯机构：[5]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery,Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China[*1]Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery,Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, No. 56 Nan-li-shi Road, Xi-Cheng District, Beijing 100045, China.
推荐引用方式(GB/T 7714)：
Ding Xu,Yang Wei,Liu Xiao-Dan,et al.Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K[J].NEUROSCIENCE.2018,385:102-120.doi:10.1016/j.neuroscience.2018.06.013.
APA：
Ding, Xu,Yang, Wei,Liu, Xiao-Dan,Yang, Xi,Wang, Huan-Min&Tai, Jun.(2018).Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K.NEUROSCIENCE,385,
MLA：
Ding, Xu,et al."Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K".NEUROSCIENCE 385.(2018):102-120
