Estrogen Receptor β Activation Is Antinociceptive in a Model of Visceral Pain in the Rat

  • Dong-Yuan Cao
    Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, Maryland
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  • Yaping Ji
    Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, Maryland
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  • Bin Tang
    Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, Maryland
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  • Richard J. Traub
    Address reprint requests to Richard J. Traub, PhD, Department of Neural and Pain Sciences, University of Maryland School of Dentistry, 650 West Baltimore Street, Baltimore, MD 21201.
    Department of Neural and Pain Sciences, School of Dentistry, University of Maryland, Baltimore, Maryland

    Program in Neuroscience, University of Maryland, Baltimore, Maryland

    Center for Pain Studies, University of Maryland, Baltimore, Maryland
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      The mechanism underlying estrogen modulation of visceral pain remains unclear. Our previous studies indicate that activation of estrogen receptor α (ERα) enhances visceral pain. The purpose of the present study was to investigate the role of estrogen receptor β (ERβ) activation in spinal processing of visceral stimuli. The effects of selective ERβ agonists on the visceromotor response (VMR) and dorsal horn neuronal responses to colorectal distention (CRD) were tested in ovariectomized and intact female rats. The magnitude of the VMR to CRD was significantly attenuated by ERβ agonists diarylpropionitrile (DPN) and WAY-200070 4 hours after subcutaneous injection. Pretreatment with the estrogen receptor antagonist ICI 182,780 obscured the DPN-evoked attenuation. There was no effect of DPN on the VMR at earlier time points. Subcutaneous and spinal administration of DPN attenuated the response of visceroceptive dorsal horn neurons with a comparable time course. DPN attenuated the VMR in intact rats regardless of estrous cycle stage. The time course of effect of ERβ activation on the visceromotor response and neuronal activity is consistent with transcriptional or translational modulation of neuronal activity.


      Activation of ERβ is antinociceptive in the colorectal distention model of visceral pain, which may provide a therapeutic target to manage irritable bowel syndrome in the clinic.

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