title: TNF-α-mediated JNK activation in the dorsal root ganglion neurons contributes to Bortezomib-induced peripheral neuropathy.
abstract: Bortezomib (BTZ) is a frequently used chemotherapeutic drug for the treatment of refractory multiple myeloma and hematological neoplasms. The mechanism by which the administration of BTZ leads to painful peripheral neuropathy remains unclear. In the present study, we first determined that the administration of BTZ upregulated the expression of TNF-α and phosphorylated JNK1/2 in the dorsal root ganglion (DRG) of rat. Furthermore, the TNF-α synthesis inhibitor thalidomide significantly blocked the activation of both isoforms JNK1 and JNK2 in the DRG and attenuated mechanical allodynia following BTZ treatment. Knockout of the expression of TNF-α receptor TNFR1 (TNFR1 KO mice) or TNFR2 (TNFR2 KO mice) inhibited JNK1 and JNK2 activation and decreased mechanical allodynia induced by BTZ. These results suggest that upregulated TNF-α expression may activate JNK signaling via TNFR1 or TNFR2 to mediate mechanical allodynia following BTZ treatment.
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Jie
authors: J
authors: Zhang
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Yi-Min
authors: YM
authors: Su
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Dai
authors: D
authors: Li
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Yu
authors: Y
authors: Cui
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Zhen-Zhen
authors: ZZ
authors: Huang
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Jia-You
authors: JY
authors: Wei
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Zi
authors: Z
authors: Xue
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Rui-Ping
authors: RP
authors: Pang
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
authors: Xian-Guo
authors: XG
authors: Liu
authors: Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China. Electronic address: xinwj@mail.sysu.edu.cn.
authors: Wen-Jun
authors: WJ
authors: Xin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001897:Boronic Acids / Q000633:toxicity*; D000069286:Bortezomib; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000201:enzymology / Q000378:metabolism; D011719:Pyrazines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D000069286:Bortezomib; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Allodynia; Bortezomib; DRG; JNK; TNF-α