title: Intrathecal injection of spironolactone attenuates radicular pain by inhibition of spinal microglia activation in a rat model.
abstract: 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-1β), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), 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-1β, TNF-α, t-NR1, and p-NR1, whereas the production of IL-6 wasn't affected.
  
  
  CONCLUSIONS
  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.
authors: Department of Anaesthesiology, Affiliated Drum-Tower Hospital of Medical College of Nanjing University, Nanjing, Jiangsu province, China.
authors: Yu-e
authors: YE
authors: Sun
authors: Liangyu
authors: L
authors: Peng
authors: Xiaofeng
authors: X
authors: Sun
authors: Jinhua
authors: J
authors: Bo
authors: Dong
authors: D
authors: Yang
authors: Yaguo
authors: Y
authors: Zheng
authors: Chenglong
authors: C
authors: Liu
authors: Beibei
authors: B
authors: Zhu
authors: Zhengliang
authors: Z
authors: Ma
authors: Xiaoping
authors: X
authors: Gu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology*; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010146:Pain / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011843:Radiculopathy / Q000150:complications / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D013148:Spironolactone / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016194:Receptors, N-Methyl-D-Aspartate; D013148:Spironolactone