Submitted on May 14, 2006
Accepted on August 16, 2006
Estrogen Rapidly Modulates Mustard Oil-induced Visceral Hypersensitivity in Conscious Female Rat: A Role of CREB Phosphorylation in Spinal Dorsal Horn Neurons
Ching-Liang Lu1*, Jen-Chuen Hsieh2, Meei-Ling Tsaur3, Yn-Ho Huang4, Paulus S Wang5, Learn-Long Wu4, Pei-Yi Liu1, Full-Young Chang1, and Shou-Dong Lee1
1 Div. Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan - Republic of China
2 Integrated Brain Research Labotratory, Taipei Veterans General Hospital, Taipei, Taiwan - Republic of China; Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan - Republic of China
3 Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan - Republic of China
4 Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan - Republic of China
5 Department of Physiology, National Yang-Ming University, Taipei, Taiwan - Republic of China
* To whom correspondence should be addressed. E-mail: cllu{at}vghtpe.gov.tw.
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 (CRD) 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 17
-estradiol (E), progesterone (P), E+P, or vehicle. Cyclic adenosine monophosphate-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 after 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 viscero-motor reflex than controls (enhanced visceral hypersensitivity), whereas ovariectomy eliminated this hypersensitivity. After a single injection of E or E+P, the rats rapidly restored MO-induced visceral hypersensitivity within 2 hours. 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 estrogen can rapidly modulate visceral hypersensitivity induced by MO intracolonic instillation in conscious female rats, which may involve spinal activation of the CRE-mediated gene induction pathway.
