TY - JOUR
T1 - Estrous cycle variation of TRPV1-mediated cross-organ sensitization between uterus and NMDA-dependent pelvic-urethra reflex activity
AU - Peng, Hsien Yu
AU - Huang, Pei Chen
AU - Liao, Jiuan Miaw
AU - Tung, Kwong Chung
AU - Lee, Shin Da
AU - Cheng, Chen Li
AU - Shyu, Jyh Cherng
AU - Lai, Cheng Yuan
AU - Chen, Gin Den
AU - Lin, Tzer Bin
PY - 2008/9
Y1 - 2008/9
N2 - 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.
AB - 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.
KW - Capsaicin
KW - Central sensitization
KW - N-methyl-D-aspartate
KW - Pelvic pain syndrome
KW - Spinal cord
KW - Spinal reflex potentiation
KW - Transient receptor potential vanilloid subfamily member 1
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UR - http://www.scopus.com/inward/citedby.url?scp=53149085275&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.90289.2008
DO - 10.1152/ajpendo.90289.2008
M3 - Article
C2 - 18577691
AN - SCOPUS:53149085275
SN - 0193-1849
VL - 295
SP - E559-E568
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
IS - 3
ER -