Feasibility of Signal Transducers and Activators of Transcription 3 Inhibitor WP1066 as a Novel Target for Neuropathic Pain
10.3969/j.issn.1674-9081.2014.02.003
- VernacularTitle:信号转导和转录激活子3抑制剂WP1066作为神经病理性疼痛治疗新靶点的可行性
- Author:
Zhao-Jing XUE
1
;
Le SHEN
;
Zhi-Yao WANG
;
Yu-Guang HUANG
Author Information
1. 中国医学科学院 北京协和医学院 北京协和医院麻醉科
- Keywords:
neuropathic pain;
JAK/STAT signaling pathway;
WP1066;
bilateral chronic sciatic nerve constriction injury
- From:
Medical Journal of Peking Union Medical College Hospital
2014;(2):142-147
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate whether the Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 ( STAT3) inhibitor WP1066 could be a novel therapeutic target for neuropathic pain and its molecu-lar mechnism.Methods Twelve female SD rats weighing 180-200 g were randomly divided into WP1066 group and control group ( n=6) using the random number table .Rats in both groups underwent bilateral chronic sciatic nerve constriction injury (bCCI).WP1066 (10μl, 10 mmol/L in dimethyl sulfoxide) or the equal volume of dime-thyl sulfoxide was applied through the intrathecal tube one day before surgery , just before surgery , and 3 and 5 days after surgery in the WP1066 group and control group , respectively .Behavior tests were performed before surgery and 3, 5, 7, 10, and 14 days after the surgery to observe the rats'reactions to mechanical , thermal, and cold stimula-tions.The rats were killed on the 14th postoperative day.The dorsal horn of the spinal cord (L4-L6) was harves-ted, followed by the reverse transcription polymerase chain reaction ( RT-PCR) and Western blotting to investigate the activation of the JAK2/STAT3 pathway.Results The pain-related behavior changes were significantly better in the WP1066 group than in the control group .WP1066 significantly inhibited the JAK2, suppressor of cytokine sig-naling 3 (SOCS3), and STAT3 mRNA in rats with bCCI, and significantly decreased the ratio of JAK2, SOCS3 and phosphorylation of STAT3 (p-STAT3) protein expression on the 14th postoperative day.Conclusions The administration of WP1066 can remarkably improve neuropathic pain in bCCI rats by inhibiting the STAT 3 signaling pathway.Therefore, WP1066 may be a novel target for neuropathic pain .
