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The effect of sinomenine in diabetic neuropathic pain mediated by the P2X3 receptor in dorsal root ganglia.

Abstract
Type 2 diabetes mellitus (T2DM) accounts for more than 90% of all cases of diabetes mellitus (DM). Diabetic neuropathic pain (DNP) is a common complication of T2DM. Sinomenine is a natural bioactive component extracted from the Sinomenium acutum and has anti-inflammatory effects. The aim of our study was to investigate the effects of sinomenine on DNP mediated by the P2X3 receptor in dorsal root ganglia (DRG). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in T2DM rats were lower than those of control rats. MWT and TWL in T2DM rats treated with sinomenine were higher compared with those in T2DM rats. The expression levels of the P2X3 protein and mRNA in T2DM rat DRG were higher compared with those of the control, while those in T2DM rats treated with sinomenine were significantly lower compared with those of the T2DM rats. Sinomenine significantly inhibited P2X3 agonist ATP-activated currents in HEK293 cells transfected with the P2X3 receptor. Sinomenine decreased the phosphorylation and activation of P38MAPK in T2DM DRG. Therefore, sinomenine treatment may suppress the up-regulated expression and activation of the P2X3 receptor and relieve the hyperalgesia potentiated by the activation of P38MAPK in T2DM rats.
AuthorsShenqiang Rao, Shuangmei Liu, Lifang Zou, Tianyu Jia, Shanhong Zhao, Bing Wu, Zhihua Yi, Shouyu Wang, Yun Xue, Yun Gao, Changshui Xu, Guilin Li, Hong Xu, Chunping Zhang, Shangdong Liang
JournalPurinergic signalling (Purinergic Signal) Vol. 13 Issue 2 Pg. 227-235 (06 2017) ISSN: 1573-9546 [Electronic] Netherlands
PMID28054206 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Morphinans
  • Purinergic P2X Receptor Antagonists
  • Receptors, Purinergic P2X3
  • sinomenine
Topics
  • Animals
  • Diabetes Mellitus, Experimental
  • Diabetes Mellitus, Type 2 (complications)
  • Diabetic Neuropathies
  • Ganglia, Spinal (drug effects)
  • HEK293 Cells
  • Humans
  • Hyperalgesia
  • Male
  • Morphinans (pharmacology)
  • Pain Threshold (drug effects)
  • Purinergic P2X Receptor Antagonists (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Purinergic P2X3 (drug effects)

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