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PAIN MECHANISMS

Estrogen Amplifies Pain Responses to Uterine Cervical Distension in Rats by Altering Transient Receptor Potential-1 Function

From the Department of Anesthesiology and the Center for the Study of Pharmacologic Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina.

Address correspondence and reprint requests to Dr. James C. Eisenach, Department of Anesthesiology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1009. Address e-mail to jim{at}eisenach.us.

Abstract

INTRODUCTION: Estrogen sensitizes responses to painful stimuli, but its contribution to acute and chronic pain from the uterine cervix is unknown. Previous studies link the excitatory transient receptor potiential-1 channel (TRPV-1) to sensitization in viscera, and show that estrogen increases TRPV-1 expression in afferents from the uterine cervix. Here, we tested whether estrogen enhanced responses to uterine cervical distension in rats, and whether this involved TRPV-1 channels.

METHODS: Ovariectomized rats, with or without estrogen replacement, were anesthetized and hypogastric nerve and abdominal muscle contraction reflex responses to graded uterine cervical distension were recorded. Single unit hypogastric nerve fiber firing was measured before and after acute treatment with the TRPV-1 antagonist, capsaizepine, or vehicle.

RESULTS: Abdominal muscle contraction reflex responses to uterine cervical distension were enhanced in estrogen-treated rats. Hypogastric afferent responses to cervical distension were reduced by capsaizepine in estrogen-treated animals, but were unaffected in ovariectomized animals without estrogen replacement.

CONCLUSIONS: These data suggest that the TRPV-1 channel is unimportant for normal mechanosensation in the cervix in the absence of estrogen, since capsaizepine failed to reduce responses to uterine cervical distension in rats without estrogen replacement. In contrast, TRPV-1 function is important for estrogen-induced sensitization. These data raise the possibility that acute and chronic pain coming from the cervix, such as labor or cancer, may be enhanced by estrogen and might be reduced by antagonists of TRPV-1.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999