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Am J Physiol Renal Physiol 295: F1324-F1335, 2008. First published July 16, 2008; doi:10.1152/ajprenal.00126.2008
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TRPV1 mediates the uterine capsaicin-induced NMDA NR2B-dependent cross-organ reflex sensitization in anesthetized rats

Hsien-Yu Peng,1,2 Hung-Ming Chang,3 Shin-Da Lee,4 Pei-Chen Huang,5 Gin-Den Chen,6 Cheng-Hung Lai,2 Cheng-Yuan Lai,1,2 Chun-Hsien Chiu,1,2 Kwong-Chung Tung,2,* and Tzer-Bin Lin1,7,8,*

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

Submitted 11 March 2008 ; accepted in final form 9 July 2008

Spinal cord-mediated cross-organ sensitization between the uterus and the lower urinary tract may underlie the high concurrence of obstetrical/gynecological inflammation and chronic pelvic pain syndrome characterized by urogenital pain. However, the neural pathway and the neurotransmitters involved are still unknown. We tested the hypothesis that the excitation of capsaicin-sensitive primary afferent fibers arising from the uterus through the stimulation of transient receptor potential vanilloid 1 (TRPV1) induces cross-organ sensitization on the pelvic-urethra reflex activity. Capsaicin (1–1,000 µM, 0.05 ml) was instilled into the uterus to induce cross-organ reflex sensitization. Activation of capsaicin-sensitive primary afferent fibers by capsaicin instillation into the uterine horn sensitized the pelvic-urethra reflex activity that was reversed by an intrauterine pretreatment with capsaizepine, a TRPV1-selective antagonist. Intrathecal injection of AP5, a glutamatergic N-methyl-D-aspartate (NMDA) antagonist, and Co-101244, an NMDA NR2B-selective antagonist, both abolished the cross-organ reflex sensitization caused by capsaicin instillation. These results demonstrated that TRPV1 plays a crucial role in contributing to the capsaicin-sensitive primary afferent fibers mediating the glutamatergic NMDA-dependent cross-organ sensitization between the uterus and the lower urinary tract when there is a tissue injury.

spinal cord; C-fiber; pain; desensitization



Address for reprint requests and other correspondence: T.B. Lin, Dept. of Physiology, College of Medicine, Chung-Shan Medical Univ., 110, Chang-Kuo North Rd., Section 1, Taichung, Taiwan 40201 (e-mail: tblin{at}csmu.edu.tw); and K.C. Tung, Dept. of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing Univ., 250, Kuo Kwang Rd., Taichung, Taiwan (e-mail: kctung1{at}dragon.nchu.edu.tw)




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Am. J. Physiol. Renal Physiol.Home page
S.-L. Chen, Y.-H. Huang, Y.-L. Kao, G.-D. Chen, C.-L. Cheng, H.-Y. Peng, J.-M. Liao, P.-C. Huang, S.-J. Tsai, and T.-B. Lin
Acute anal stretch inhibits NMDA-dependent pelvic-urethra reflex potentiation via spinal GABAergic inhibition in anesthetized rats
Am J Physiol Renal Physiol, October 1, 2008; 295(4): F923 - F931.
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