Crude alkaloidal extraction from Gelsemium elegans Benth. produces
analgesic property. However, its clinical utility has been obstructed by its narrow therapeutic index. Here, we investigated the potential of
koumine, a monomer of Gelsemium
alkaloids, to reduce both inflammatory and
neuropathic pain. Interestingly,
allopregnanolone, a
neurosteroid, appeared to mediate the reduction of
neuropathic pain. The potential anti-inflammatory
pain effects of
koumine were evaluated by
acetic acid-,
formalin- and complete
Freund's adjuvant (CFA) -induced nociceptive behaviors in mice. Chronic constriction injury (CCI) and L5 spinal nerve
ligation (L5 SNL), inducing
thermal hyperalgesia and
mechanical allodynia in rats, were used to test whether repeated treatment of
koumine ameliorated
neuropathic pain. Finally, we explored if
koumine altered the level of
neurosteroids in rat spinal cord of CCI neuropathy using liquid chromatography-tandem mass spectrometry.
Koumine dose-dependently reduced the
acetic acid-induced writhes and
formalin-induced licking/biting time of Phase II in mice. Repeated administrations of
koumine also dose-dependently reversed the CFA-, CCI- and L5 SNL-induced
thermal hyperalgesia, as well as, CCI- and L5 SNL-induced
mechanical allodynia in rats. The level of
allopregnanolone, but not
pregnenolone, in the L5-6 spinal cord was elevated by repeated treatment of
koumine in CCI-induced neuropathic rats. These results demonstrate that
koumine has a significant
analgesic effect in rodent behavioral models of inflammatory and
neuropathic pain, and that the reduction in
neuropathic pain may be associated with the upregulation of
allopregnanolone in the spinal cord.