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Am J Physiol Gastrointest Liver Physiol 292: G438-G446, 2007. First published September 14, 2006; doi:10.1152/ajpgi.00210.2006
0193-1857/07 $8.00
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Estrogen rapidly modulates mustard oil-induced visceral hypersensitivity in conscious female rats: a role of CREB phosphorylation in spinal dorsal horn neurons

Ching-Liang Lu,1 Jen-Chuen Hsieh,2,3 Meei-Ling Tsaur,3 Yn-Ho Huang,4 Paulus S. Wang,5 Learn-Long Wu,4 Pei-Yi Liu,1 Full-Young Chang,1 and Shou-Dong Lee1

1Division of Gastroenterology; 2Integrated Brain Research Laboratory, Department of Medical Research and Education, Taipei Veterans General Hospital; and 3Institute of Neuroscience, 4Institute of Anatomy and Cell Biology, and 5Department of Physiology, National Yang-Ming University School of Medicine, Taipei, Taiwan

Submitted 14 May 2006 ; accepted in final form 16 August 2006

ABSTRACT

This study investigated the effect of sex hormones on mustard oil (MO)-induced visceral hypersensitivity in female rats and analyzed possible involved signaling pathways. Female rats, either intact or ovariectomized (OVX), were prepared for abdominal muscle electromyography in response to colorectal distension after intracolonic instillation of MO. The effect of MO intracolonic sensitization was evaluated in intact rats, OVX rats, and OVX rats pretreated with a single injection of 17beta-estradiol (E), progesterone (P), E+P, or vehicle. cAMP-responsive element-binding protein (CREB) and phosphorylated CREB (pCREB) were detected in the superficial dorsal horn of L6 and S1 in MO or mineral oil-treated OVX rats with/without colorectal distension and estrogen replacement. The distal colorectum was removed for histological evaluation of inflammatory severity in MO-treated intact or OVX rats. The MO-treated rats had significantly higher visceromotor reflex than controls (enhanced visceral hypersensitivity), whereas OVX eliminated this hypersensitivity. After a single injection of E or E+P, the rats rapidly restored MO-induced visceral hypersensitivity within 2 h. Estrogen also rapidly induced a dose-dependent increase in pCREB expression in the superficial dorsal horn neurons in MO-treated, but not mineral oil-treated, OVX rats. The present study suggests that estrogen can rapidly modulate visceral hypersensitivity induced by MO intracolonic instillation in conscious female rats, which may involve spinal activation of the cAMP response element-mediated gene induction pathway.

irritable bowel syndrome; spinal cord; cAMP-response element binding protein; gender


Address for reprint requests and other correspondence: C.-L. Lu, Division of Gastroenterology, Dept. of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Rd., Taipei, Taiwan 11217 (e-mail: cllu{at}vghtpe.gov.tw)






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