Broad modulation of neuropathic pain states by a selective estrogen receptor beta agonist.
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.
ACADIA Pharmaceuticals Inc, San Diego, CA, USA. fpiu@acadia-pharm.com
Fabrice
F
Piu
Cindy
C
Cheevers
Lene
L
Hyldtoft
Luis R
LR
Gardell
Andria L
AL
Del Tredici
Carsten B
CB
Andersen
Luke C
LC
Fairbairn
Birgitte W
BW
Lund
Magnus
M
Gustafsson
Hans H
HH
Schiffer
John E
JE
Donello
Roger
R
Olsson
Daniel W
DW
Gil
Mark R
MR
Brann
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047629:Estrogen Receptor beta / Q000819:agonists*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014599:Uterus / Q000187:drug effects
D047629:Estrogen Receptor beta; D000077267:Fulvestrant; D004958:Estradiol