ABSTRACT
To understand the contribution of the estrogen receptor beta, the potent and selective agonist ERb-131 was evaluated in animal models of inflammatory pain. In paradigms of acute and persistent inflammatory pain, ERb-131 did not alleviate the nociception induced by either carrageenan or formalin. However, in the chronic complete Freund's adjuvant model, ERb-131 resolved both inflammatory and hyperalgesic components. Thus, ERb-131 is sufficient to alleviate chronic but not acute inflammatory pain states.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal , Estrogen Receptor beta/agonists , Inflammation/drug therapy , Pain/drug therapy , Acute Disease , Animals , Carrageenan , Chronic Disease , Formaldehyde , Freund's Adjuvant , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Inflammation/chemically induced , Inflammation/etiology , Male , Pain/chemically induced , Pain/etiology , Pain Measurement/drug effects , Rats , Rats, Sprague-DawleyABSTRACT
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.