Cyclophosphamide induces NR2B phosphorylation-dependent facilitation on spinal reflex potentiation

Chao Hsiang Chang, Hsien Yu Peng, Hsi Chin Wu, Cheng Yuan Lai, Ming Chun Hsieh, Tzer Bin Lin

研究成果: 雜誌貢獻文章

6 引文 斯高帕斯(Scopus)

摘要

It is well-established that cyclophosphamide (CYP) can sensitize the pelvic afferent nerve arising from the urinary bladder and therefore induce suprapubic pain. To test the possibility that CYP might mediate the development of visceral hypereflexia/hyperalgesia by facilitating spinal activity-dependent neural plasticity, we compared the pelvic-urethra reflex activity and spinal N-methyl-D-aspartate receptor NR2B subunit (NR2B) phosphorylation in rats treated with vehicle solution and CYP. Compared with vehicle solution, when accompanied by upregulation of phosphorylated NR2B expression in the lumbosacral (L6-S2) dorsal horn, CYP increased the evoked spikes in spinal reflex potentiation induced by repetitive stimulation (1 stimulation/1 s). Moreover, intraperitoneal pretreatments with NG-nitro-L-arginine methyl ester and roscovitine, nitric oxide synthase and cyclin-dependent protein kinase 5 (Cdk5) antagonists, respectively, overwrote CYP-enhanced reflex potentiation and NR2B phosphorylation. When compared with the untreated group, the treatment with small-interfering RNA of NR2B, which decreased the expression of NR2B expression, abolished CYP-dependent reflex facilitation and spinal NR2B phosphorylation. These results suggested that CYP might facilitate spinal reflex potentiation mediated by N-methyl-D-aspartate receptors and participate in the development of visceral hypereflexia/hyperalgesia through nitric oxide- and Cdk5-dependent NR2B phosphorylation at the lumbo-sacral dorsal horn.

原文英語
期刊American Journal of Physiology - Renal Physiology
300
發行號3
DOIs
出版狀態已發佈 - 三月 1 2011
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Physiology
  • Urology

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