PMID- 21106858
OWN - NLM
STAT- MEDLINE
DCOM- 20110420
LR  - 20161125
IS  - 1522-1466 (Electronic)
IS  - 1522-1466 (Linking)
VI  - 300
IP  - 3
DP  - 2011 Mar
TI  - Cyclophosphamide induces NR2B phosphorylation-dependent facilitation on spinal 
      reflex potentiation.
PG  - F692-9
LID - 10.1152/ajprenal.00531.2010 [doi]
AB  - 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 (L(6)-S(2)) 
      dorsal horn, CYP increased the evoked spikes in spinal reflex potentiation 
      induced by repetitive stimulation (1 stimulation/1 s). Moreover, intraperitoneal 
      pretreatments with N(G)-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 lumbosacral dorsal horn.
FAU - Chang, Chao-Hsiang
AU  - Chang CH
AD  - 1Department of Urology, China Medical University Hospital, College of Medicine, 
      China.
FAU - Peng, Hsien-Yu
AU  - Peng HY
FAU - Wu, Hsi-Chin
AU  - Wu HC
FAU - Lai, Cheng-Yuan
AU  - Lai CY
FAU - Hsieh, Ming-Chun
AU  - Hsieh MC
FAU - Lin, Tzer-Bin
AU  - Lin TB
LA  - eng
PT  - Journal Article
DEP - 20101124
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 8N3DW7272P (Cyclophosphamide)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*pharmacology
MH  - Cyclin-Dependent Kinase 5/metabolism
MH  - Cyclophosphamide/*pharmacology
MH  - Evoked Potentials/drug effects/physiology
MH  - Female
MH  - Models, Animal
MH  - Nitric Oxide/metabolism
MH  - Phosphorylation/drug effects
MH  - Posterior Horn Cells/drug effects/metabolism
MH  - RNA, Small Interfering/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Reflex/*drug effects/*physiology
MH  - Spinal Nerves/drug effects/*physiology
EDAT- 2010/11/26 06:00
MHDA- 2011/04/22 06:00
CRDT- 2010/11/26 06:00
PHST- 2010/11/26 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/04/22 06:00 [medline]
AID - ajprenal.00531.2010 [pii]
AID - 10.1152/ajprenal.00531.2010 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2011 Mar;300(3):F692-9. doi: 
      10.1152/ajprenal.00531.2010. Epub 2010 Nov 24.