Overexpression of suppressor of cytokine signaling 3 in dorsal root ganglion attenuates cancer-induced pain in rats.
Background Cancer-induced pain (CIP) is one of the most severe types of chronic pain with which clinical treatment remains challenging and the involved mechanisms are largely unknown. Suppressor of cytokine signaling 3 (SOCS3) is an important intracellular protein and provides a classical negative feedback loop, thus involving in a wide variety of processes including inflammation and nociception. However, the role of SOCS3 pathway in CIP is poorly understood. The present study was designed to investigate the role of SOCS3 in dorsal root ganglion (DRG) in the development of CIP. Method CIP was established by injection of Walker 256 mammary gland tumor cells into the rat tibia canal. Whole-cell patch clamping and Western blotting were performed. Results Following the development of bone cancer, SOCS3 expression was significantly downregulated in rat DRGs at L2-L5 segments. Overexpression of SOCS3, using lentiviral-mediated production of SOCS3 at spinal cord level, drastically attenuated mechanical allodynia and body weight-bearing difference, but not thermal hyperalgesia in bone cancer rats. In addition, overexpression of SOCS3 reversed the hyperexcitability of DRG neurons innervating the tibia, and reduced abnormal expression of toll-like receptors 4 in the DRGs. Conclusions These results suggest that SOCS3 might be a key molecular involved in the development of complicated cancer pain and that overexpression of SOCS3 might be an important strategy for treatment for mechanical allodynia associated with bone cancer.
1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, P.R. China.
Jinrong
J
Wei
1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, P.R. China.
Meng
M
Li
1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, P.R. China.
Dieyu
D
Wang
2 Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, P.R. China.
Hongyan
H
Zhu
1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, P.R. China.
Xiangpeng
X
Kong
2 Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, P.R. China.
Shusheng
S
Wang
1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, P.R. China.
You-Lang
YL
Zhou
1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, P.R. China.
Zhong
Z
Ju
1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, P.R. China.|2 Center for Translational Medicine, Affiliated Zhangjiagang Hospital of Soochow University, Zhangjiagang, P.R. China.
Guang-Yin
GY
Xu
1 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, The Second Affiliated Hospital, Soochow University, Suzhou, P.R. China.
Guo-Qin
GQ
Jiang
D000818:Animals; D000072716:Cancer Pain / Q000503:physiopathology / Q000628:therapy*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology*; D015316:Genetic Therapy / Q000379:methods*; D006930:Hyperalgesia / Q000209:etiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D017288:Pain Threshold / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism*; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D016474:Weight-Bearing / Q000502:physiology
D016207:Cytokines; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; C530472:TLR3 protein, rat; D051196:Toll-Like Receptor 3
Cancer-induced pain; dorsal root ganglion; suppressor of cytokine signaling 3; toll-like receptors 4