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This Article Full Text Full Text (PDF) All Versions of this Article: 297/2/E416    most recent 00129.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Peng, H.-Y. Articles by Lin, T.-B. PubMed PubMed Citation Articles by Peng, H.-Y. Articles by Lin, T.-B.

Estrogen-dependent facilitation on spinal reflex potentiation involves the Cdk5/ERK1/2/NR2B cascade in anesthetized rats

¹Department of Physiology, ⁴Graduate Institute of Medicine, College of Medicine, ³Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital, Chung-Shan Medical University; ²Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University; ⁵Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University; ⁶Department of Healthcare Administration, Asia University, Taichung; ⁷Medical Department, Saint Paul's Hospital, Taoyuan; and ⁸Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan

Submitted 27 February 2009 ; accepted in final form 28 May 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) β-estradiol facilitated the repetitive stimulation-induced SRP that was reversed by pretreatment with the estrogen receptor anatogonist ICI 182,780 (10 nM, 10 µl it), Cdk5 inhibitor roscovitine (100 nM, 10 µl it), ERK inhibitor (U-0126; 100 µM, 10 µl it) and N-methyl-D-aspartate (NMDA) NR2B subunit antagonist (Co-101244; 100 nM, 10 µl it). Moreover, ER (propylpyrazoletriol; 100 nM, 10 µl it) and ERβ (diarylpropionitrile; 100 µM, 10 µl it) agonists both facilitated the SRP, similar to results with a β-estradiol injection. In association with the facilitated RS-induced SRP, an intrathecal β-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 and ERβ, may subsequently phosphorylate the NR2B subunit to develop NMDA-dependent postinflammatory hyperalgesia and allodynia to maintain the protective mechanisms of the body.

estradiol; cyclin-dependent kinase-5; NR2B; extracellular signal-related kinase; pelvic pain; spinal reflex potentiaton; hyperalgesia