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Koumine enhances spinal cord 3α-hydroxysteroid oxidoreductase expression and activity in a rat model of neuropathic pain.
Mol Pain. 2015 Aug 09; 11:46.MP

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, College of Pharmacy, Fujian Medical University, 350108, Fuzhou, Fujian, People's Republic of China. honjohn@126.com.Department of Pharmacology, College of Pharmacy, Fujian Medical University, 350108, Fuzhou, Fujian, People's Republic of China. 43959098@qq.com. Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People's Republic of China. 43959098@qq.com.Department of Pharmacology, College of Pharmacy, Fujian Medical University, 350108, Fuzhou, Fujian, People's Republic of China. jinguilin0611@163.com.Department of Pharmacology, College of Pharmacy, Fujian Medical University, 350108, Fuzhou, Fujian, People's Republic of China. fjmukent@163.com. Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, People's Republic of China. fjmukent@163.com.Department of Pharmacology, College of Pharmacy, Fujian Medical University, 350108, Fuzhou, Fujian, People's Republic of China. 601836366@qq.com.Department of Pharmacology, College of Pharmacy, Fujian Medical University, 350108, Fuzhou, Fujian, People's Republic of China. 6564678@qq.com.Department of Pharmacology, College of Pharmacy, Fujian Medical University, 350108, Fuzhou, Fujian, People's Republic of China. changxiyu@mail.fjmu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26255228

Citation

Qiu, Hong-Qiang, et al. "Koumine Enhances Spinal Cord 3α-hydroxysteroid Oxidoreductase Expression and Activity in a Rat Model of Neuropathic Pain." Molecular Pain, vol. 11, 2015, p. 46.
Qiu HQ, Xu Y, Jin GL, et al. Koumine enhances spinal cord 3α-hydroxysteroid oxidoreductase expression and activity in a rat model of neuropathic pain. Mol Pain. 2015;11:46.
Qiu, H. Q., Xu, Y., Jin, G. L., Yang, J., Liu, M., Li, S. P., & Yu, C. X. (2015). Koumine enhances spinal cord 3α-hydroxysteroid oxidoreductase expression and activity in a rat model of neuropathic pain. Molecular Pain, 11, 46. https://doi.org/10.1186/s12990-015-0050-1
Qiu HQ, et al. Koumine Enhances Spinal Cord 3α-hydroxysteroid Oxidoreductase Expression and Activity in a Rat Model of Neuropathic Pain. Mol Pain. 2015 Aug 9;11:46. PubMed PMID: 26255228.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Koumine enhances spinal cord 3α-hydroxysteroid oxidoreductase expression and activity in a rat model of neuropathic pain. AU - Qiu,Hong-Qiang, AU - Xu,Ying, AU - Jin,Gui-Lin, AU - Yang,Jian, AU - Liu,Ming, AU - Li,Su-Ping, AU - Yu,Chang-Xi, Y1 - 2015/08/09/ PY - 2015/03/11/received PY - 2015/07/28/accepted PY - 2015/8/10/entrez PY - 2015/8/10/pubmed PY - 2016/3/10/medline SP - 46 EP - 46 JF - Molecular pain JO - Mol Pain VL - 11 N2 - 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. SN - 1744-8069 UR - https://www.unboundmedicine.com/medline/citation/26255228/Koumine_enhances_spinal_cord_3α_hydroxysteroid_oxidoreductase_expression_and_activity_in_a_rat_model_of_neuropathic_pain_ L2 - https://journals.sagepub.com/doi/10.1186/s12990-015-0050-1?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -