• Ying Zang, Shao-Xia Chen, Guang-Jie Liao, He-Quan Zhu, Xu-Hong Wei, Yu Cui, Xiao-Dong Na, Rui-Ping Pang, Wen-Jun Xin, Li-Jun Zhou, and Xian-Guo Liu.
• Pain Research Center and Department of Physiology, Zhongshan Medical School of Sun Yat-Sen University, 74 Zhongshan Rd. 2, Guangzhou 510080, China. Electronic address: zangying@mail.sysu.edu.cn.
• Brain Behav. Immun. 2015 Feb 1; 44: 37-47.

AbstractMotor nerve injury by L5 ventral root transection (L5-VRT) initiates interleukin-6 (IL-6) up-regulation in primary afferent system contributing to neuropathic pain. However, the early upstream regulatory mechanisms of IL-6 after L5-VRT are still unknown. Here, we monitored both the activity of calpain, a calcium-dependent protease suggested as one of the earliest mediators for cytokine regulation, and the expression of IL-6 in bilateral L4-L6 dorsal root ganglias (DRGs) soon after L5-VRT. We found that the protein level of calpain-2 in DRGs, but not calpain-1 was increased transiently in the first 10 min(-1)h ipsilaterally and 20 min(-1)h contralaterally after L5-VRT, long before mechanical allodynia was initiated (5-15 h ipsilaterally and 15 h(-1)d contralaterally). The early activation of calpain evaluated by the generation of spectrin breakdown products (SBDP) correlated well with IL-6 up-regulation in bilateral DRGs. Double immunofluorescence staining revealed that almost all the calpain-2 positive neurons expressed IL-6, indicating an association between calpain-2 and IL-6. Inhibition of calpain by pre-treatment with MDL28170 (25mg/kg, i.p.) attenuated the rat mechanical allodynia and prevented the early up-regulation of IL-6 following L5-VRT. Addition of exogenous calpain-2 onto the surface of left L5 DRG triggered a temporal allodynia and increased IL-6 in bilateral DRGs simultaneously. Taken together, the early increase of calpain-2 in L5-VRT rats might be responsible for the induction of allodynia via up-regulating IL-6 in DRG neurons.Copyright © 2014 Elsevier Inc. All rights reserved.

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