ESTROGEN RECEPTORS BETA AND ALPHA HAVE SPECIFIC PRO- AND ANTI-NOCICEPTIVE ACTIONS

It is strongly suggested that estrogen plays a key role in pain modulation. Estrogen's effects are mediated mainly by two receptors, ER alpha and ER beta. However, the specific role of these receptors is still not clear. In this study, the involvement of both receptors on nociceptive responses was measured in ER alpha and ER beta knockout (KO) C57BL/6j mice and their respective wild type (WT) littermate (male and female). It was also measured in four groups of ovariectomized mice injected for 7 days with either (1) vehicle, (2) 17 beta-estradiol, (3) ER alpha-selective agonist propylpyrazoletriol (PPT) or (4) ER beta-selective agonist diarylpropionitril (DPN). As previously described, ER beta KO females showed lower nociceptive responses compared to WT female mice during the interphase and early tonic phase 2 of the formalin test. The observed pronociceptive nature of ER beta was confirmed using ER beta-selective agonist DPN injections in ovariectomized mice. Moreover, we found that ER alpha KO male and female mice presented a small increase in nociceptive behaviors during phase 1 of the formalin test, suggesting an anti-nociceptive effect of ER alpha. These results were confirmed by the injection of ER alpha-selective agonist PPT in ovariectomized mice. Interestingly, both ER agonists reduced nociceptive responses during late phase 2, suggesting an anti-inflammatory action of estrogen. Results were supported by spinal c-Fos immunohistochemistry. In conclusion, both ER alpha and ER beta appear to be involved in pain transmission and modulation but may be acting at distinct levels of the pain pathways. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.