Analgesic effects and pharmacologic mechanisms of the Gelsemium alkaloid koumine on a rat model of postoperative pain

Abstract

Postoperative pain (POP) of various durations is a common complication of surgical procedures. POP is caused by nerve damage and inflammatory responses that are difficult to treat. The neuroinflammation-glia-steroid network is known to be important in POP. It has been reported that the Gelsemium alkaloid koumine possesses analgesic, anti-inflammatory and neurosteroid modulating activities. This study was undertaken to test the analgesic effects of koumine against POP and explore the underlying pharmacologic mechanisms. Our results showed that microglia and astroglia were activated in the spinal dorsal horn post-incision, along with an increase of proinflammatory cytokines (interleukin 1β, interleukin 6, and tumor necrosis factor α). Both subcutaneous and intrathecal (i.t.) koumine treatment after incision significantly prevented mechanical allodynia and thermal hyperalgesia, inhibited microglial and astroglial activation, and suppressed expression of proinflammatory cytokines. Moreover, the analgesic effects of koumine were antagonized by i.t. administration of translocator protein (18 kDa) (TSPO) antagonist PK11195 and GABAA receptor antagonist bicuculline. Together, koumine prevented mechanical allodynia and thermal hyperalgesia caused by POP. The pharmacologic mechanism of koumine-mediated analgesia might involve inhibition of spinal neuroinflammation and activation of TSPO. These data suggested that koumine might be a potential pharmacotherapy for the management of POP.

Orally Administered Koumine Persists Longer in the Plasma of Aged Rats Than That of Adult Rats as Assessed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

“…Koumine (KM), the most abundant alkaloid in Gelsemium elegans Benth. ( G. elegans ) has various pharmacological properties and is known to be effective in the treatment of numerous age-associated conditions including postoperative pain ( Xiong et al., 2017 ; Shoaib et al., 2019 ), inflammation ( Yuan et al., 2016 ; Wu et al., 2020 ), rheumatoid arthritis ( Yang et al., 2016 ), malignant tumors ( Yuan et al., 2019a ), nonalcoholic fatty liver disease ( Yue et al., 2019 ), oxidative stress ( Yuan et al., 2019b ), and neuropathic pain ( Jin et al., 2018a ; Jin et al., 2018b ). However, the pharmacokinetic profile of KM in the elderly or aged animals remains to be fully evaluated.…”

Koumine Decreases Astrocyte-Mediated Neuroinflammation and Enhances Autophagy, Contributing to Neuropathic Pain From Chronic Constriction Injury in Rats

“…We recently reported the analgesic effect of koumine in various animal pain models, such as chronic constriction injury (CCI), spared nerve injury, diabetic NP, and rheumatoid arthritis pain models (Xu et al, 2012; Ling et al, 2014; Qiu et al, 2015; Yang et al, 2016; Xiong et al, 2017; Jin et al, 2018a). Koumine displayed high efficiency and low toxicity in the treatment of NP, implying that this compound may have potential as a new anti-NP drug.…”

Ultra-Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS)-Based Pharmacokinetics and Tissue Distribution Study of Koumine and the Detoxification Mechanism of Glycyrrhiza uralensis Fisch on Gelsemium elegans Benth.

“…As the most abundant molecule among the alkaloids of G. elegans , koumine (KM) has been demonstrated to exert numerous potent biological properties, such as anxiolytic and analgesic effects [ 8 ]. However, it also possesses inhibitory effects on splenocyte proliferation and the humoral immune response [ 9 ].…”