Calpain-2 contributes to neuropathic pain following motor nerve injury via up-regulating interleukin-6 in DRG neurons.

Abstract

Motor 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.

• Authors: 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, Xian-Guo Liu
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 44 Pg. 37-47 (Feb 2015) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 25150005 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Interleukin-6
• Spectrin
• Calpain

Topics

• Animals
• Calpain (metabolism, pharmacology)
• Ganglia, Spinal (enzymology)
• Hyperalgesia (enzymology, etiology)
• Interleukin-6 (metabolism)
• Male
• Neuralgia (enzymology, etiology)
• Neurons (enzymology)
• Rats
• Rats, Sprague-Dawley
• Spectrin (metabolism)
• Spinal Nerve Roots (injuries)
• Up-Regulation