Effects of immobilization stress and hormonal treatment on nociception

The purpose of this study was to evaluate the effects of stress and estradiol (E2) on pain tolerance. Ovariectomized rats were assigned to treatment groups based on a 2 x 4 factorial design comprising stress (nonstress x stress) and hormone treatment vehicle x E2 [0.25 mg/kg/d]) x estrogen receptor alpha (ERalpha)-selective agonist propyl pyrazole triol (1 mg/kg/d) x estrogen receptor beta (ERbeta)-selective agonist diarylpropionitrile (1 mg/kg/d). Stressed animals underwent daily 60-minute immobilization for 22 days. Pain tolerance was assessed with the hot plate test, an acute thermal pain test. In this study, stressed rats showed increased (P < .05) pain tolerance compared with nonstressed rats (25.0 +/- 1.92 s vs 20.4 +/- 1.02 s, respectively). Increased (P < .05) pain threshold was observed in nonstressed and stressed rats treated with E2 and the ERalpha agonist compared with vehicle-treated rats. Interestingly, the ERbeta agonist only increased (P < .10) pain thresholds in stressed rats. Stressed rats exhibited higher (P < .05) beta-endorphin levels compared with nonstressed rats in all hormone-treatment groups. With the exception of stressed rats treated with the ERbeta agonist, there was no hormone effect on beta-endorphin levels. These studies suggest that E2's effect on pain thresholds may be mediated via the ERalpha, while the interaction between chronic stress and ERbeta may also enhance pain threshold.