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Brain Behav Immun. 2014 May;38:185-91. doi: 10.1016/j.bbi.2014.01.020. Epub 2014 Feb 13.

TNF-α-mediated JNK activation in the dorsal root ganglion neurons contributes to Bortezomib-induced peripheral neuropathy.

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  • 1Department of Physiology and Pain Research Center, Zhongshan Medical School, Sun Yet-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China.
  • 2Department 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.

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Allodynia; Bortezomib; DRG; JNK; TNF-α

[PubMed - indexed for MEDLINE]
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