Overexpression of suppressor of cytokine signaling 3 in dorsal root ganglion attenuates cancer-induced pain in rats

• Published in: Molecular pain Vol. 13; p. 1744806916688901
• Main Authors: Wei, Jinrong, Li, Meng, Wang, Dieyu, Zhu, Hongyan, Kong, Xiangpeng, Wang, Shusheng, Zhou, You-Lang, Ju, Zhong, Xu, Guang-Yin, Jiang, Guo-Qin
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01.01.2017; Sage Publications Ltd
• Subjects: Animals; Body weight; Bone cancer; Cancer Pain - physiopathology; Cancer Pain - therapy; Cells, Cultured; Chronic pain; Cytokines; Cytokines - metabolism; Disease Models, Animal; Dorsal root ganglia; Down-Regulation - drug effects; Down-Regulation - genetics; Female; Ganglia, Spinal - cytology; Ganglia, Spinal - physiology; Genetic Therapy - methods; Hyperalgesia; Hyperalgesia - etiology; Intracellular signalling; Mammary gland; Membrane Potentials - drug effects; Membrane Potentials - genetics; Pain; Pain perception; Pain Threshold - physiology; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells - drug effects; Sensory Receptor Cells - physiology; SOCS-3 protein; Spinal cord; Statistics, Nonparametric; Suppressor of Cytokine Signaling 3 Protein - genetics; Suppressor of Cytokine Signaling 3 Protein - metabolism; Tibia; Toll-Like Receptor 3 - metabolism; Toll-like receptors; Tumor cells; Weight-Bearing - physiology; Western blotting; Cancer-induced pain; suppressor of cytokine signaling 3; toll-like receptors 4; dorsal root ganglion
• ISSN: 1744-8069; 1744-8069
• DOI: 10.1177/1744806916688901

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.