Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/32970
標題: Estrogen-dependent facilitation on spinal reflex potentiation involves the Cdk5/ERK1/2/NR2B cascade in anesthetized rats
作者: Peng, H.Y.
董光中
Chen, G.D.
Tung, K.C.
Chien, Y.W.
Lai, C.Y.
Hsieh, M.C.
Chiu, C.H.
Lai, C.H.
Lee, S.D.
Lin, T.B.
關鍵字: estradiol
cyclin-dependent kinase-5
NR2B
extracellular signal-related
kinase
pelvic pain
spinal reflex potentiaton
hyperalgesia
activated protein-kinase
long-term potentiation
element-binding
protein
d-aspartate receptor
signal-regulated kinase
dorsal-horn
neurons
synaptic plasticity
map kinase
pain hypersensitivity
central
sensitization
期刊/報告no:: American Journal of Physiology-Endocrinology and Metabolism, Volume 297, Issue 2, Page(s) E416-E426.
摘要: Peng HY, Chen GD, Tung KC, Chien YW, Lai CY, Hsieh MC, Chiu CH, Cheng HL, Lee SD, Lin TB. Estrogen-dependent facilitation on spinal reflex potentiation involves the Cdk5/ERK1/2/NR2B cascade in anesthetized rats. Am J Physiol Endocrinol Metab 297: E416-E426, 2009. First published June 16, 2009; doi: 10.1152/ajpendo.00129.2009. Cyclin-dependent kinase-5 (Cdk5), a proline-directed serine/threonine kinase, may alter pain-related neuronal plasticity by regulating extracellular signal-related kinase-1/2 (ERK1/2) activation. This study investigated whether Cdk5-dependent ERK activation underlies the estrogen-elicited facilitation on the repetitive stimulation-induced spinal reflex potentiaton (SRP) that is presumed to be involved in postinflammatory/neuropathic hyperalgesia and allodynia. Reflex activity of the external urethra sphincter electromyogram evoked by pelvic afferent nerve test stimulation (TS; 1 stimulation/30 s for 10 min) and repetitive stimulation (RS; 1 stimulation/1 s for 10 min) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP. Intrathecal (it) beta-estradiol facilitated the repetitive stimulation-induced SRP that was reversed by pretreatment with the estrogen receptor anatogonist ICI 182,780 (10 nM, 10 mu l it), Cdk5 inhibitor roscovitine (100 nM, 10 mu l it), ERK inhibitor (U-0126; 100 mu M, 10 mu l it) and N-methyl-D-aspartate (NMDA) NR2B subunit antagonist (Co-101244; 100 nM, 10 mu l it). Moreover, ER alpha (propylpyrazoletriol; 100 nM, 10 mu l it) and ER alpha (diarylpropionitrile; 100 mu M, 10 mu l it) agonists both facilitated the SRP, similar to results with a beta-estradiol injection. In association with the facilitated RS-induced SRP, an intrathecal beta-estradiol injection elicited ERK1/2 and NR2B subunit phosphorylation that were both reversed by intrathecal roscovitine and U-0126. These results indicated that the Cdk/ERK cascade, which is activated by ER alpha and ER beta, may subsequently phosphorylate the NR2B subunit to develop NMDA-dependent postinflammatory hyperalgesia and allodynia to maintain the protective mechanisms of the body.
URI: http://hdl.handle.net/11455/32970
ISSN: 0193-1849
文章連結: http://dx.doi.org/10.1152/ajpendo.00129.2009
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