Paeoniflorin inhibits excitatory amino acid agonist-and high-dose morphine-induced nociceptive behavior in mice via modulation of N-methyl-D-aspartate receptors

Abstract

BackgroundPain, the most common reasons for physician consultation, is a major symptom in many medical conditions that can significantly interfere with a person’s life quality and general functioning. Almost all painkillers have its untoward effects. Therefore, seeking for a safe medication for pain relieve is notable nowadays. Paeonia lactiflora is a well-known traditional Chinese medicine. Paeoniflorin is an active component found in Paeonia lactiflora, which has been reported to inhibit formalin-induced nociceptive behavior in mice. Aims of this present study were to investigate effects of paeoniflorin on excitatory amino acid agonist- or high-dose morphine-induced nociceptive behaviors in mice.ResultsPaeoniflorin (100, 200, 500 nmol, i.c.v.) alone and combined with glutamatergic antagonists (MK-801 14.8 pmol, or NBQX 5 nmol, i.t.) inhibited nociception. Those agents also inhibited the clonic seizure-like excitation induced by high-dose morphine (250 nmol, i.t) in mice. Antisense oligodeoxynucleotides of NMDA receptor subunits NR1, NR2A, NR2B significantly enhanced the inhibition of paeoniflorin on excitatory amino acid-and high-dose morphine-induced nociception. Docking energy data revealed that paeoniflorin had stronger binding activity in NR2A and NR2B than NR2C of NMDA receptors.ConclusionsResults of this study indicate that paeoniflorin-induced inhibition of excitatory amino acid agonist- and high-dose morphine-induced nociceptive behaviors might be due to modulation of NMDA receptors, specifically the NR2B subunit.

Paeoniflorin Attenuates Inflammatory Pain by Inhibiting Microglial Activation and Akt-NF-κB Signaling in the Central Nervous System

“…But as NSAIDs often cause severe gastrointestinal adverse effects, it is necessary to find new analgesic drugs with minimal adverse effects. The research showed that PF had good anti-inflammatory and analgesic effects, especially when it was used in combination with morphine [26,27]. Nevertheless, the analgesic mechanism of PF is poorly understood yet.…”

“…PF can improve CNS diseases such as cognitive impairment, depression, and Parkinson's disease [21][22][23][24][25]. The combined use of PF and opioid analgesics could potentiate the analgesic effect of opioid analgesics in the treatment of cancerous pain as compared with the use of opioid analgesics alone [26,27]. Our previous study demonstrated that PF exerted the anti-inflammatory effect by inhibiting the activation of microglia [28].…”

Guizhi Fuling Capsule Exhibits Antidysmenorrhea Activity by Inhibition of Cyclooxygenase Activity

“…Paeoniflorin attenuates neuropathic pain via MAP-kinase pathway [29]. It also mediates neuroprotective effect, hence ameliorating the function of cholinergic nerve [30][31][32]. Paeoniflorin also relieves oxidative stress and downregulates NF-κB expression, hence damping proinflammatory cytokine production [33].…”

Herbal medicine for hand–foot syndrome induced by fluoropyrimidines: A systematic review and meta‐analysis

“…It also inhibited inflammatory pain via modulation of N‐methyl‐D‐aspartate in the brain cortex and reduced related cytokines, such as tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, IL‐6, IL‐10, IL‐12, and IL‐17 (Dai et al, ; Sun et al, ; Xu et al, ). Paeoniflorin upregulated apoptosis of MGC‐803 human gastric carcinoma cells and HT29 human colorectal cancer cells (Chen, Lee, et al, ; Parker et al, ; Zheng et al, ). It inhibited proliferation, invasion, and metastasis of MCF‐7/MDA‐MB‐231 human breast cancer cells and human A549 lung cancer cells (Parker et al, ; Zhang, Yuan, Cui, Xiao, & Jiang, ; Zhou, Wang, Song, & Hu, ).…”