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

Yuh-Fung Chen,Yu-Chien Chen,Ming-Ming Lee,Huei-Yann Tsai,Jhao-Guei Yang,Hsun-Lang Fang

doi:10.1186/s12906-016-1230-x

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.

Highlights

Pain, 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
It is well-established that the NMDA receptor NMDA receptor subunit 2B (NR2B) subunit is an important contributor to pain mechanisms
Effects of PF and MK-801 on formalin-induced licking and biting behavior Figure 3 shows that different concentrations of PF (100, 200, 500 nmol, i.c.v.) caused significant inhibition in both early (0–5 min) and late (10–30 min) phases of formalin-induced licking and biting behavior of mice

Summary

Introduction

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. 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. Several reports are indicating that the NR2B subunit is involved in mediating pain [21,22,23] and learning. It is well-established that the NMDA receptor NR2B subunit is an important contributor to pain mechanisms. Identifying selective NR2B antagonistic drugs is a priority in pain management [24]

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Conclusion