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PLoS By Category | Recent PLoS Articles
Anesthesiology and Pain Management - Pharmacology - Physics - Physiology

Intrathecal Injection of Spironolactone Attenuates Radicular Pain by Inhibition of Spinal Microglia Activation in a Rat Model
Published: Friday, June 29, 2012
Author: Yu-e Sun et al.

by Yu-e Sun, Liangyu Peng, Xiaofeng Sun, Jinhua Bo, Dong Yang, Yaguo Zheng, Chenglong Liu, Beibei Zhu, Zhengliang Ma, Xiaoping Gu

Background

Microglia might play an important role in nociceptive processing and hyperalgesia by neuroinflammatory process. Mineralocorticoid receptor (MR) expressed on microglia might play a central role in the modulation of microglia activity. However the roles of microglia and MR in radicular pain were not well understood. This study sought to investigate whether selective MR antagonist spironolactone develop antinociceptive effects on radicular pain by inhibition neuroinflammation induced by spinal microglia activation.

Results

Radicular pain was produced by chronic compression of the dorsal root ganglia with SURGIFLO™. The expression of microglia, interleukin beta (IL-1ß), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-a), NR1 subunit of the NMDA receptor (t-NR1), and NR1 subunit phosphorylated at Ser896 (p-NR1) were also markedly up-regulated. Intrathecal injection of spironolactone significantly attenuated pain behaviors as well as the expression of microglia, IL-1ß, TNF-a, t-NR1, and p-NR1, whereas the production of IL-6 wasn’t affected.

Conclusion

These results suggest that intrathecal delivery spironolactone has therapeutic effects on radicular pain in rats. Decreasing the activation of glial cells, the production of proinflammatory cytokines and down-regulating the expression and phosphorylation of NMDA receptors in the spinal dorsal horn and dorsal root ganglia are the main mechanisms contributing to its beneficial effects.

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