Spinal SHP2 Contributes to Exaggerated Incisional Pain in Adult Rats Subjected to Neonatal and Adult Incisions via PI3K

Publication date: 10 August 2018Source: Neuroscience, Volume 385Author(s): Xu Ding, Wei Yang, Xiao-Dan Liu, Xi Yang, Huan-Min Wang, Jun TaiAbstractNeonatal 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 expressio...

Source: Neuroscience - July 10, 2018 Category: Neuroscience Source Type: research