Sex Steroids Localized to the Amygdala Increase Pain Responses to Visceral Stimulation in Rats

  • Brent Myers
    Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

    Veterans Affairs Medical Center, Oklahoma City, Oklahoma
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  • Jay Schulkin
    Department of Physiology and Biophysics, Georgetown University, Washington, District of Columbia

    Research Department, American College of Obstetricians and Gynecologists, Washington, District of Columbia

    Molecular Imaging Branch, National Institute of Mental Health, Bethesda, Maryland
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  • Beverley Greenwood-Van Meerveld
    Address reprint requests to Beverley Greenwood-Van Meerveld, PhD, FACG, VA Medical Center, Research Administration Rm. 151, 921 NE 13th Street, Oklahoma City, OK 73104.
    Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

    Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma

    Veterans Affairs Medical Center, Oklahoma City, Oklahoma
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Published:December 20, 2010DOI:


      Females are disproportionately affected by irritable bowel syndrome (IBS) with menstrual cycle-dependent fluctuations in abdominal pain suggesting a role for ovarian hormones. IBS patients also exhibit greater activation of brain areas involved in pain affect such as the amygdala, yet the role of supraspinal processes in the effects of ovarian hormones on visceral pain is largely unexplored. The goal of the current study was to determine whether sex steroids act at the level of the amygdala to alter colonic pain sensitivity. Ovariectomized rats received implants on the amygdala of progesterone, estradiol, progesterone combined with estradiol, or cholesterol as a control to examine the involvement of the amygdala in ovarian hormone-mediated changes in visceral sensitivity. Visceral sensitivity was quantified as the number of abdominal contractions, a visceromotor response (VMR), in response to graded pressures of colorectal distension (CRD). Somatic sensitivity was also assessed by measuring the mechanical force required to elicit hindpaw withdrawal. Elevated levels of progesterone and/or estradiol on the amygdala heightened the responsiveness to CRD; in contrast, neither estradiol nor progesterone altered somatic sensation. Furthermore, administration of progesterone or estradiol to areas adjacent to the amygdala did not affect visceral sensitivity. Future studies will address the specific steroid receptors mediating the effects of progesterone and estradiol.


      To our knowledge, this study represents the first description of a specific brain site mediating the effects of ovarian steroids on visceral sensitivity. These data also suggest that an amygdala-dependent mechanism may be responsible, at least in part, for the exacerbation of visceral symptomatology in females.

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