Pronociceptive actions of isoflurane: a protective role for estrogen.

Background: Low concentrations of inhaled anesthetics present in the early postoperative period can increase pain sensitivity. Changes in pain threshold associated with inhaled anesthetics have been reported in male mice, rats, and humans.

Methods: The authors compared the pain-enhancing effects of isoflurane in male and female mice in response to a thermal stimulus and studied the consequences of hormonal manipulation.

Results: Isoflurane produced a larger increase in pain sensitivity in female mice. Both castration and oophorectomy resulted in an increase in baseline pain sensitivity and potentiated pain enhancement by isoflurane. At stages of the estrus cycle when estrogen was low, female mice showed greater pain enhancement from isoflurane than at high estrogen stages. Treatment with exogenous estrogen reduced isoflurane-induced pain sensitivity. Exogenous testosterone treatment had a similar effect, which did not occur when enzymatic conversion to estrogen was prevented.

Conclusions: Because both estrogen and testosterone reduce the pronociceptive action of isoflurane, intact females may exhibit a larger increase in pain sensitivity because of their cyclical estrogen levels. Testosterone is effective in the male because of conversion to estrogen. Enhanced pain sensitivity is clearly undesirable in the postoperative setting. If these findings also apply to humans, the menstrual cycle may be an important factor in determining pain levels after emergence from general anesthesia.