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Estrogen receptor α regulates the IKKs/NF-kB activity involved in the development of mechanical allodynia induced by REM sleep deprivation in rats.

Authors :
Martínez-Magaña, Carlos J.
Murbartián, Janet
Source :
Brain Research. Dec2024, Vol. 1845, pN.PAG-N.PAG. 1p.
Publication Year :
2024

Abstract

[Display omitted] • BMS-345541 avoided the development of REMSD-induced allodynia in female rats. • BMS-345541 did not avoid the development of REMSD-induced allodynia in male rats. • ERα antagonism or run-down of ERα in female rats abolished BMS-345541′s effect. • REMSD increased ERα protein expression in DRG/DSC in females but not in male rats. • ERα activation or ERα overexpression allowed the effect of BMS-345541 in male rats. Several signaling pathways that converge in NF-kB activation have been linked to developing and maintaining different types of pathological pain. In addition, some mechanisms implied in the establishment of chronic pain have been demonstrated to have a sex-dependent correlation. This study aimed to determine if the IKKs/NF-kB signaling pathway is involved in establishing REM sleep deprivation (REMSD) induced mechanical allodynia in rats and its possible regulation depending on estradiol and estrogen receptors. Intrathecal administration of BMS-345541 or minocycline, two drugs that reduce the IKKs/NF-kB activity, avoided the development of mechanical allodynia in female but not in male rats subjected to 48 h of REMSD. Ovariectomy in female rats abolished the effect of BMS-345541 and minocycline. Meanwhile, the 17-β-estradiol restitution restored it. Intrathecal administration of MPP, a selective ERα antagonist, but not PHTPP, a selective ERβ antagonist, avoided the effect of BMS-345541 in female rats without hormonal manipulation. In addition, the transient run-down of ERα in female rats abolished the effect of BMS-345541. All data suggest an important role of ERα as a regulator of the IKKs/NF-kB activity. REMSD increased the ERα protein expression in the dorsal root ganglia and the dorsal spinal cord in females but not in male rats. Interestingly, ERα activation or ERα overexpression allowed the effect of BMS-345541 in male rats. Data suggest an important regulatory role of ERα in the IKKs/NF-kB activity on establishing mechanical allodynia induced by REMSD in female rats. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00068993
Volume :
1845
Database :
Academic Search Index
Journal :
Brain Research
Publication Type :
Academic Journal
Accession number :
180883065
Full Text :
https://doi.org/10.1016/j.brainres.2024.149269