Estrous cycle variation of TRPV1-mediated cross-organ sensitization between uterus and NMDA-dependent pelvic-urethra reflex activity.
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 microM in both the proestrus and metestrus stages, whereas they weakened when the concentrations were higher than 1,000 microM. 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.
Peng
Hsien-Yu
HY
Dept. of Physiology, College of Medicine, Chung-Shan Medical University, Taichung, Taiwan 40201.
Huang
Pei-Chen
PC
Liao
Jiuan-Miaw
JM
Tung
Kwong-Chung
KC
Lee
Shin-Da
SD
Cheng
Chen-Li
CL
Shyu
Jyh-Cherng
JC
Lai
Cheng-Yuan
CY
Chen
Gin-Den
GD
Lin
Tzer-Bin
TB
D000818:Animals; D015153:Blotting, Western; D002211:Capsaicin / Q000494:pharmacology; D030762:Estrous Cycle / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D007278:Injections, Spinal; D016202:N-Methylaspartate / Q000502:physiology; D017699:Pelvic Pain / Q000503:physiopathology; D010766:Phosphorylation; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D012018:Reflex / Q000502:physiology*; D050916:TRPV Cation Channels / Q000187:drug effects / Q000502:physiology*; D014521:Urethra / Q000187:drug effects / Q000502:physiology*; D014570:Urologic Diseases / Q000503:physiopathology; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D016202:N-Methylaspartate; D002211:Capsaicin