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

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number3
DOIs
Publication statusPublished - Mar 1 2011
Externally publishedYes

Fingerprint

Cyclophosphamide
Reflex
Phosphorylation
Cyclin-Dependent Kinase 5
Cyclin-Dependent Kinases
Hyperalgesia
Neuronal Plasticity
NG-Nitroarginine Methyl Ester
Urethra
N-Methyl-D-Aspartate Receptors
Nitric Oxide Synthase
Small Interfering RNA
Nitric Oxide
Urinary Bladder
Up-Regulation
Pain

Keywords

  • Cyclin-dependent protein kinase 5
  • N-methyl-d-aspartate receptor NR2B subunit
  • Nitric oxide
  • Pelvic nerve
  • Urethra
  • Visceral pain

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Cyclophosphamide induces NR2B phosphorylation-dependent facilitation on spinal reflex potentiation. / Chang, Chao Hsiang; Peng, Hsien Yu; Wu, Hsi Chin; Lai, Cheng Yuan; Hsieh, Ming Chun; Lin, Tzer Bin.

In: American Journal of Physiology - Renal Physiology, Vol. 300, No. 3, 01.03.2011.

Research output: Contribution to journalArticle

Chang, Chao Hsiang ; Peng, Hsien Yu ; Wu, Hsi Chin ; Lai, Cheng Yuan ; Hsieh, Ming Chun ; Lin, Tzer Bin. / Cyclophosphamide induces NR2B phosphorylation-dependent facilitation on spinal reflex potentiation. In: American Journal of Physiology - Renal Physiology. 2011 ; Vol. 300, No. 3.
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