Eur J Pharmacol. 2008 May 23. [Epub ahead of print]
Broad modulation of neuropathic pain states by a selective estrogen receptor beta agonist.
Piu F, Cheevers C, Hyldtoft L, Gardell LR, Del Tredici AL, Andersen CB, Fairbairn LC, Lund BW, Gustafsson M, Schiffer HH, Donello JE, Olsson R, Gil DW, Brann MR.
ACADIA Pharmaceuticals Inc, San Diego, CA, USA.
The effects of estrogens on pain perception remain controversial. In animal models, both beneficial and detrimental effects of non-selective estrogens have been reported. ERb-131 a non-steroidal estrogen receptor beta ligand was evaluated in several pain animal models involving nerve injury or sensitization. Using functional and binding assays, ERb-131 was characterized as a potent and selective estrogen receptor beta agonist. In vivo, ERb-131 was devoid of estrogen receptor alpha activity as assessed in a rat uterotrophic assay. ERb-131 alleviated tactile hyperalgesia induced by capsaicin, and reversed tactile allodynia caused by spinal nerve ligation and various chemical insults. Moreover, ERb-131 did not influence the pain threshold of normal healthy animals. Thus, estrogen receptor beta agonism is a critical effector in attenuating a broad range of anti-nociceptive states. |
