Tags

Type your tag names separated by a space and hit enter

Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K.
Neuroscience. 2018 08 10; 385:102-120.N

Abstract

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.

Authors+Show Affiliations

Nutrition Research Unit, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.Department of Pathology, Peking University, Beijing, China.Department of Laboratory Medicine, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.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. Electronic address: taibch@sina.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29909075

Citation

Ding, Xu, et al. "Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions Via PI3K." Neuroscience, vol. 385, 2018, pp. 102-120.
Ding X, Yang W, Liu XD, et al. Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K. Neuroscience. 2018;385:102-120.
Ding, X., Yang, W., Liu, X. D., Yang, X., Wang, H. M., & Tai, J. (2018). Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K. Neuroscience, 385, 102-120. https://doi.org/10.1016/j.neuroscience.2018.06.013
Ding X, et al. Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions Via PI3K. Neuroscience. 2018 08 10;385:102-120. PubMed PMID: 29909075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K. AU - Ding,Xu, AU - Yang,Wei, AU - Liu,Xiao-Dan, AU - Yang,Xi, AU - Wang,Huan-Min, AU - Tai,Jun, Y1 - 2018/06/15/ PY - 2018/01/04/received PY - 2018/05/23/revised PY - 2018/06/07/accepted PY - 2018/6/18/pubmed PY - 2019/2/23/medline PY - 2018/6/18/entrez KW - PI3K KW - SHP2 KW - incisional pain KW - neonate KW - spinal dorsal horn SP - 102 EP - 120 JF - Neuroscience JO - Neuroscience VL - 385 N2 - 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. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/29909075/Spinal_SHP2_Contributes_to_Exaggerated_Incisional_Pain_in_Adult_Rats_Subjected_to_Neonatal_and_Adult_Incisions_via_PI3K_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(18)30424-X DB - PRIME DP - Unbound Medicine ER -