Koumine enhances spinal cord 3α-hydroxysteroid oxidoreductase expression and activity in a rat model of neuropathic pain

Molecular Pain

Chang-Xi Yu²  Su-Ping Li²  Ming Liu²  Jian Yang¹  Gui-Lin Jin²  Ying Xu¹  Hong-Qiang Qiu² 

[1] Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China;Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, 350108, Fujian, People’s Republic of China

关键词: 3α-Hydroxysteroid dehydrogenase;    Allopregnanolone;    Neurosteroids;    Neuropathic pain;    Koumine;   

Others  :  1226133
DOI  :  10.1186/s12990-015-0050-1

 received in 2015-03-11, accepted in 2015-07-28,  发布年份 2015

【 摘 要 】

Background

Koumine is an alkaloid monomer found abundantly in Gelsemium plants. It has been shown to reverse thermal hyperalgesia and mechanical allodynia induced by sciatic nerve chronic constriction injury (CCI) in rats in a dose-dependent manner. Interestingly, this effect is mediated by elevated allopregnanolone levels in the spinal cord (SC). Since 3α-hydroxysteroid oxidoreductase (3α-HSOR), the key synthetase of allopregnanolone, is responsible for allopregnanolone upregulation in the SC, the objective of the present study was to investigate the role of its expression in the SC in koumine-induced analgesia using a rat model of neuropathic pain following peripheral nerve injury.

Results

Time-course investigations of immunohistochemistry and real-time polymerase chain reaction revealed that the immunoreactivity and mRNA expression of 3α-HSOR markedly increased in a time-dependent manner in the SC of koumine-treated CCI rats. Furthermore, 3α-HSOR activity in the SC of koumine-treated CCI rats increased by 15.8% compared to the activity in untreated CCI rats. Intrathecal injection of medroxyprogesterone acetate, a selective 3α-HSOR inhibitor, reversed the analgesic effect of koumine on CCI-induced mechanical pain perception. Our results confirm that koumine alleviates neuropathic pain in rats with CCI by enhancing 3α-HSOR mRNA expression and bioactivity in the SC.

Conclusion

This study demonstrates that 3α-HSOR is an important molecular target of koumine for alleviating neuropathic pain. Koumine may prove a promising compound for the development of novel analgesic agents effective against intractable neuropathic pain.

【 授权许可】

   
2015 Qiu et al.

【 图 表 】

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