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標題: Neuroactive steroids inhibit spinal reflex potentiation by selectively enhancing specific spinal GABA(A) receptor subtypes
作者: Peng, H.Y.
Chen, G.D.
Lee, S.D.
Lai, C.Y.
Chiu, C.H.
Cheng, C.L.
Chang, Y.S.
Hsieh, M.C.
Tung, K.C.
Lin, T.B.
關鍵字: Progesterone;Pain;Hyperalgesia;Spinal cord;Estrus cycle;estrogen and/or progesterone;anesthetized rats;neurosteroid;modulation;delta-subunit;5-alpha-reduced metabolites;dentate gyrus;ovarian cycle;anxiety;neurons;pain
Project: Pain
期刊/報告no:: Pain, Volume 143, Issue 1-2, Page(s) 12-20.
Recently, we demonstrated a spinal GABA(A) receptor (GABA(A)R)-dependent inhibition on the induction of repetitive simulation-induced spinal reflex potentiation. However, it remains unclear whether steroid hormones modulate such an inhibition. Here, we show that progesterone is capable of producing GABA(A)Rs-dependent inhibition of the induction of spinal reflex potentiation by actions through neurosteroid metabolites. Progesterone (5 mg/kg, twice daily for 4 days) up-regulates the expression of GABA(A)R alpha 2, alpha 3, alpha 4 and delta subunits, and is associated with attenuated repetitive stimulation-induced spinal reflex activity in ovariectomized rats. These changes were blocked by finasteride (50 mg/kg, twice daily), an antagonist of neurosteroid synthesis from progesterone, but not by the progesterone receptor antagonist, RU486 (100 mg/kg, twice daily). The induction of spinal reflex potentiation was attenuated after a short (30 min) intrathecal treatment with the neurosteroids, allopregnanolone (ALLOP, 10 mu M, 10 mu L) and 3 alpha,5 alpha-tetrahydrodeoxycorticosterone (THDOC, 10 mu M, 10 mu L). Acute intrathecal administration of the GABA(A)R antagonist, bicuculline (10 mu M, 10 mu L) reversed the inhibition produced by progesterone,THDOC and allopregnanolone. These results imply that progesterone-mediated effects oil GABAAR expression and neural inhibition are regulated by neurosteroids synthesis rather, than progesterone receptor activation. (C) 2009 International Association for tire Study of Pain. Published by Elsevier B.V. All rights reserved.
ISSN: 0304-3959
DOI: 10.1016/j.pain.2008.12.023
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