Orexin-A modulates glutamatergic NMDA-dependent spinal reflex potentiation via inhibition of NR2B subunit

被引:21
|
作者
Peng, Hsien-Yu [1 ,2 ]
Chang, Hung-Ming [3 ]
Chang, Sarah Y. [5 ]
Tung, Kwong-Chung [1 ]
Lee, Shin-Da [6 ]
Chou, Dylan [2 ]
Lai, Cheng-Yuan [1 ,2 ]
Chiu, Chun-Hsien [1 ,2 ]
Chen, Gin-Den [4 ]
Lin, Tzer-Bin [2 ,7 ,8 ]
机构
[1] Natl Chung Hsing Univ, Dept Vet Med, Coll Vet Med, Taichung 40227, Taiwan
[2] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Physiol, Taichung, Taiwan
[3] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Anat, Coll Med, Taichung, Taiwan
[4] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Obstet & Gynecol, Taichung, Taiwan
[5] Tunghai Univ, Dept Chem, Taichung 40704, Taiwan
[6] China Med Univ, Coll Med, Sch Phys Therapy, Taichung, Taiwan
[7] St Pauls Hosp, Dept Med, Tao Yuan, Taiwan
[8] Natl Taiwan Univ, Grad Inst Biomed Elect & Bioinformat, Taipei 10764, Taiwan
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2008年 / 295卷 / 01期
关键词
spinal cord; pelvic nerve; urethra; rats;
D O I
10.1152/ajpendo.90243.2008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Glucose-sensitive neurons in the lateral hypothalamic area produce orexin-A (OxA) as well as orexin-B (OxB) and send their axons to the spinal dorsal horn, which predominantly expresses orexin receptor-1 (OX-1), showing a higher sensitivity to OxA. The purpose of the present study was to assess the effects of OxA on the induction of a novel form of activity-dependent reflex potentiation, spinal reflex potentiation (SRP), in the pelvic-urethral reflex activity. External urethra sphincter electromyogram in response to pelvic afferent nerve test stimulation (TS; 1/30 Hz) or repetitive stimulation (RS; 1 Hz) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP, which was abolished by intrathecal OxA (30 nM, 10 mu l). Intrathecal SB-408124 (10 mu M, 10 mu l), an OX-1 antagonist, reversed the abolition on SRP caused by OxA. Although there is, so far, no NR2A-and NR2B-specific agonist available, N-methyl-D-aspartate (NMDA) reversed the abolition on the RS-induced SRP caused by the coadministration of OxA and Co-101244 (30 nM, 10 mu l; an NMDA NR2B subunit antagonist), but it did not reverse the abolition by the co-administration of OxA and PPPA (300 nM, 10 mu l; an NMDA NR2A subunit antagonist). In conclusion, the activation of descending orexinergic fibers may inhibit the repetitive afferent input-induced central sensitization of pelvic-urethral reflex activity and urethra hyperactivity, indicating that spinal orexinergic neural transmission may be a novel target for the treatment of patients with neuropathetic or postinflammatory pain of pelvic origin.
引用
收藏
页码:E117 / E129
页数:13
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