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Gelsemine and koumine, principal active ingredients of Gelsemium, exhibit mechanical antiallodynia via spinal glycine receptor activation-induced allopregnanolone biosynthesis.
Abstract Gelsemine, the principal active alkaloid from Gelsemium sempervirens Ait., and koumine, the most dominant alkaloids from Gelsemium elegans Benth., produced antinociception in a variety of rodent models of painful hypersensitivity. The present study explored the molecular mechanisms underlying gelsemine- and koumine-induced mechanical antiallodynia in neuropathic pain. The radioligand binding and displacement assays indicated that gelsemine and koumine, like glycine, were reversible and orthosteric agonists of glycine receptors with full efficacy and probably acted on same binding site as the glycine recep...
Source: Biochemical Pharmacology - January 19, 2019 Category: Drugs & Pharmacology Authors: Shoaib RM, Zhang JY, Mao XF, Wang YX Tags: Biochem Pharmacol Source Type: research

Cynandione A attenuates neuropathic pain through p38 β MAPK-mediated spinal microglial expression of β-endorphin
This study aims to evaluate the antihypersensitivity activities of cynandione A in neuropathy and explored its mechanisms of action. Intrathecal injection of cynandione A dose-dependently attenuated spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia, with maximal possible effects of 57% and 59%, ED50s of 14.9 μg and 6.5 μg, respectively. Intrathecal injection of cynandione A significantly increased β-endorphin levels in spinal cords of neuropathic rats and its treatment concentration-dependently induced β-endorphin expression in cultured primary microglia (but not in neurons or astrocytes), wit...
Source: Brain, Behavior, and Immunity - February 8, 2017 Category: Neurology Source Type: research

Cynandione A attenuates neuropathic pain through p38 β MAPK-mediated spinal microglial expression of β-endorphin.
This study aims to evaluate the antihypersensitivity activities of cynandione A in neuropathy and explored its mechanisms of action. Intrathecal injection of cynandione A dose-dependently attenuated spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia, with maximal possible effects of 57% and 59%, ED50s of 14.9 μg and 6.5 μg, respectively. Intrathecal injection of cynandione A significantly increased β-endorphin levels in spinal cords of neuropathic rats and its treatment concentration-dependently induced β-endorphin expression in cultured primary microglia (but not in neurons or astrocytes), wit...
Source: Brain, Behavior, and Immunity - February 7, 2017 Category: Neurology Authors: Huang Q, Mao XF, Wu HY, Liu H, Sun ML, Wang X, Wang YX Tags: Brain Behav Immun Source Type: research

Extracellular caspase-6 drives murine inflammatory pain via microglial TNF-α secretion
Increasing evidence indicates that the pathogenesis of neuropathic pain is mediated through spinal cord microglia activation. The intracellular protease caspase-6 (CASP6) is known to regulate neuronal apoptosis and axonal degeneration; however, the contribution of microglia and CASP6 in modulating synaptic transmission and pain is unclear. Here, we found that CASP6 is expressed specifically in C-fiber axonal terminals in the superficial spinal cord dorsal horn. Animals exposed to intraplantar formalin or bradykinin injection exhibited CASP6 activation in the dorsal horn. Casp6-null mice had normal baseline pain, but impair...
Source: Journal of Clinical Investigation - February 17, 2014 Category: Biomedical Science Authors: Temugin Berta, Chul-Kyu Park, Zhen-Zhong Xu, Ruo-Gang Xie, Tong Liu, Ning Lü, Yen-Chin Liu, Ru-Rong Ji Source Type: research