Neuroactive steroids inhibit spinal reflex potentiation by selectively enhancing specific spinal GABA(A) receptor subtypes

作者：Peng Hsien Yu; Chen Gin Den; Lee Shin Da; Lai Chen Yuan; Chiu Chun Hsien; Cheng Chen Li; Chang Yu Shuo; Hsieh Ming Chun; Tung Kwong Chung; Lin Tzer Bin^*

来源：Pain, 2009, 143(1-2): 12-20.

DOI：10.1016/j.pain.2008.12.023

• Progesterone
• Pain
• Hyperalgesia
• Spinal cord
• Estrus cycle

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.

• 出版日期2009-5
• 单位中国医科大学