Author(s): Peng, HY (Peng, Hsien-Yu); Chen, GD (Chen, Gin-Den); Tung, KC (Tung, Kwong- Chung); Chien, YW (Chien, Ya-wen); Lai, CY (Lai, Cheng-Yuan); Hsieh, MC (Hsieh, Ming- Chun); Chiu, CH (Chiu, Chun-Hsien); Lai, CH (Lai, Cheng-Hung); Lee, SD (Lee, Shin-Da); Lin, TB (Lin, Tzer-Bin)
Title: Estrogen-dependent facilitation on spinal reflex potentiation involves the Cdk5/ERK1/2/NR2B cascade in anesthetized rats
Source: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 297 (2): E416-E426 AUG 2009
Language: English Document Type: Article
Author Keywords: estradiol; cyclin-dependent kinase-5; NR2B; extracellular signal-related kinase; pelvic pain; spinal reflex potentiaton; hyperalgesia
KeyWords Plus: 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
Abstract: 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.
Addresses: [Peng, Hsien-Yu; Lai, Cheng-Yuan; Hsieh, Ming-Chun; Lin, Tzer-Bin] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Physiol, Coll Med, Taichung 40201, Taiwan; [Chien, Ya-wen] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Grad Inst Med, Coll Med, Taichung 40201, Taiwan; [Chen, Gin-Den] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Obstet & Gynecol, Taichung 40201, Taiwan; [Peng, Hsien-Yu; Tung, Kwong-Chung; Lai, Cheng-Yuan; Chiu, Chun-Hsien; Lai, Cheng-Hung] Natl Chung Hsing Univ, Coll Vet Med, Dept Vet Med, Taichung 40227, Taiwan; [Lee, Shin-Da] China Med Univ, Grad Inst Rehabil Sci, Dept Phys Therapy, Taichung, Taiwan; [Lee, Shin-Da] Asia Univ, Dept Healthcare Adm, Taichung, Taiwan; [Lin, Tzer-Bin] St Pauls Hosp, Dept Med, Tao Yuan, Taiwan; [Lin, Tzer-Bin] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 10764, Taiwan
Reprint Address: Lin, TB, Chung Shan Med Univ, Dept Physiol, Coll Med, 110 Chang Kuo N Rd 1st Sect, Taichung 40201, Taiwan.
E-mail Address: [email protected] Funding Acknowledgement:
Funding Agency Grant Number
National Science Council of Taiwan NSC 97-2320-B-008-MY3
This research was supported by the National Science Council of Taiwan NSC 97-2320-B- 008-MY3 to T.-B. Lin.
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Publisher: AMER PHYSIOLOGICAL SOC
Publisher Address: 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA ISSN: 0193-1849
DOI: 10.1152/ajpendo.00129.2009
29-char Source Abbrev.: AMER J PHYSIOL-ENDOCRINOL MET ISO Source Abbrev.: Am. J. Physiol.-Endocrinol. Metab.
Source Item Page Count: 11
Subject Category: Endocrinology & Metabolism; Physiology ISI Document Delivery No.: 473ZT
