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doi: 10.1097/ALN.0b013e3182a66e94
Pain Medicine: Basic Science

Acute Uterine Irritation Provokes Colonic Motility via Transient Receptor Potential A1-dependent Spinal NR2B Phosphorylation in Rats

Peng, Hsien-Yu Ph.D.; Yeh, Chou-Ming M.D., M.Sc.; Cheng, Jen-Kun M.D., Ph.D.; Chau, Yat-Pang Ph.D.; Ruan, Ting Ph.D.; Chen, Gin-Den M.D.; Hsieh, Ming-Chun M.Sc.; Lai, Cheng-Yuan B.S.; Lin, Tzer-Bin Ph.D.

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Background: Patients with inflammatory gynecological/obstetrical problems often complain of irritable bowel syndrome. The authors examined whether acute uterus irritation reflexively provokes colonic motility in rat preparations.
Methods: A modified colon manometry and striated abdominal muscle electromyogram activity in response to mustard oil (MO) instillation into the uterine horn were continuously recorded in anesthetized rats. The lumbosacral (L6-S1) dorsal horn was dissected to assess the level and the cellular location of phosphorylated NR2B subunit using Western blotting and immunofluorescence analysis, respectively. Finally, the uterine transient receptor potential A1 or spinal NR2B subunit was pharmacologically blocked to elucidate its roles.
Results: MO (0.1%, 0.2 ml) injected into the lower uterine horn dramatically provoked colonic hypermotility characterized by rhythmic colonic contractions (about 3–4 contractions per 10 min, n = 7) accompanied by synchronized electromyogram firing in the abdominal muscle (about 4–5 folds of control, n = 7). In addition to provoking colonic hypermotility, MO administration also up-regulated phosphorylated (about 2–3 folds of control, n = 7), but not total, NR2B expression in the dorsal horn neurons. Both intrathecal Ro 25–6981 (a selective NR2B subunit antagonist; 10 μM, 10 μl) and intrauterine HC-030031 (a selective transient receptor potential A1 receptor antagonist; 30 mg/kg, 0.2 ml) injected before the MO instillation attenuated the MO-induced colonic hypermotility and spinal NR2B phosphorylation.
Conclusion: The comorbidity of gynecological/obstetrical and gastrointestinal problems is not coincidental but rather causal in nature, and clinicians should investigate for gynecological/urological diseases in the setting of bowel problems with no known pathological etiology.

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