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

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: Hong-Qiang Qiu, Ying Xu, Gui-Lin Jin, Jian Yang, Ming Liu, Su-Ping Li, Chang-Xi Yu
• Journal: Molecular pain (Mol Pain) Vol. 11 Pg. 46 (Aug 09 2015) ISSN: 1744-8069 [Electronic] United States
• PMID: 26255228 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Indole Alkaloids
• RNA, Messenger
• koumine
• Medroxyprogesterone Acetate
• 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)

Topics

• 3-alpha-Hydroxysteroid Dehydrogenase (B-Specific) (antagonists & inhibitors, genetics, metabolism)
• Analgesics (pharmacology, therapeutic use)
• Animals
• Biocatalysis (drug effects)
• Chronic Disease
• Constriction
• Disease Models, Animal
• Gene Expression Regulation, Enzymologic (drug effects)
• Hyperalgesia (complications, drug therapy, pathology)
• Immunohistochemistry
• Indole Alkaloids (administration & dosage, chemistry, pharmacology, therapeutic use)
• Injections, Subcutaneous
• Male
• Medroxyprogesterone Acetate (pharmacology)
• Neuralgia (complications, drug therapy, enzymology, genetics)
• RNA, Messenger (genetics, metabolism)
• Rats, Sprague-Dawley
• Sciatic Nerve (drug effects, enzymology, pathology)
• Spinal Cord (drug effects, enzymology, pathology)
• Spinal Cord Dorsal Horn (drug effects, enzymology, pathology)