Estrogen modulation of ovariectomy-induced hyperalgesia in adult mice

Some chronic pain conditions are more prevalent in women. However, the evidence from both human and animal studies as to whether estrogen is pro- or anti-nociceptive is inconsistent. We have used a model of functional abdominal pain in mice to examine the role of estrogen in the modulation of a hyperalgesic state induced by ovariectomy. C57/BL6 female mice were either ovariectomized (OVX), received the same surgery without removing the ovaries or were tested without any surgical procedure. Mechanical hyperalgesia was assessed by von Frey filaments and thermal pain was measured using a hot-plate at 50 °C. OVX mice, but not sham-operated, developed mechanical hyperalgesia localized to the abdominal region, the hindlimbs and the proximal tail, 4-5 weeks after OVX as well as a reduction in response latency to the hot plate. OVX animals were implanted with 17β-estradiol pellets or with similar pellets with no hormone five weeks after OVX, when the hyperalgesic state was fully developed, and the estrogen reversed both mechanical and thermal hyperalgesia. Vaginal smears were taken to record the phase of the cycle at the time of the test from all animals and no significant differences were detected in mechanical hyperalgesia or in thermal pain threshold between normal animals in different phases of their estrous cycle. These results show that OVX induces a hyperalgesic state of slow onset and long duration that can be reversed by estrogen. We have also observed no estrous cycle modulation of pain sensitivity in normal animals.