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1Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University; 2Department of Physiology, College of Medicine, and 3Department of Obstetrics and Gynecology, Chung-Shan Medical University Hospital, Chung-Shan Medical University, Taichung; 4Department of Obstetrics and Gynecology, Chang-Gung Memorial Hospital, Taoyuan; 5School of Physical Therapy, College of Medicine, China Medical University; 6Division of Urology, Department of Surgery, Taichung Veterans General Hospital, Taichung; 7Department of Medicine, Saint Paul's Hospital, Taoyuan; and 8Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan
Submitted 13 March 2008 ; accepted in final form 19 June 2008
Cross-organ sensitization between the uterus and the lower urinary tract (LUT) underlies the high concurrence of pelvic pain syndrome and LUT dysfunctions, and yet the role of gonadal steroids is still unknown. We tested the hypothesis that cross-organ sensitization on pelvic-urethra reflex activity caused by uterine capsaicin instillation is estrous cycle dependent. When compared with the baseline reflex activity (1.00 ± 0.00 spikes/stimulation), uterine capsaicin instillation significantly increased reflex activity (45.42 ± 9.13 spikes/stimulation, P < 0.01, n = 7) that was corroborated by an increase in phosphorylated NMDA NR2B (P < 0.05, n = 4) but not NR2A subunit (P > 0.05, n = 4) expression. Both intrauterine pretreatment with capsazepine (5.02 ± 2.11 spikes/stimulation, P < 0.01, n = 7) and an intrathecal injection of AP5 (3.21 ± 0.83 spikes/stimulation, P < 0.01, n = 7) abolished the capsaicin-induced cross-organ sensitization and the increment in the phosphorylated NR2B level (P < 0.05, n = 4). The degrees of the cross-organ sensitization increased in a dose-dependent manner with the concentration of instilled capsaicin from 100 to 300 µM in both the proestrus and metestrus stages, whereas they weakened when the concentrations were higher than 1,000 µM. Moreover, the cross-organ sensitization caused by the uterine capsaicin instillation increased significantly in the rats during the proestrus stage when compared with the metestrus stage (P < 0.01, n = 7). These results suggest that estrogen levels might modulate the cross-organ sensitization between the uterus and the urethra and underlie the high concurrence of pelvic pain syndrome and LUT dysfunctions.
transient receptor potential vanilloid subfamily member 1; N-methyl-D-aspartate; pelvic pain syndrome; central sensitization; spinal reflex potentiation; capsaicin; spinal cord
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