title: Paeoniflorin inhibits excitatory amino acid agonist-and high-dose morphine-induced nociceptive behavior in mice via modulation of N-methyl-D-aspartate receptors.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  Paeoniflorin (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.
  
  
  CONCLUSIONS
  Results 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.
authors.affiliation: Department of Pharmacology, China Medical University, No 91, Hsueh-Shih Road, Taichung, 40402, Taiwan. yfchen@mail.cmu.edu.tw.|Department of Pharmacy, China Medical University Hospital, No 2, Yu-Der Road, Taichung, 40431, Taiwan. yfchen@mail.cmu.edu.tw.
authors.forename: Yuh-Fung
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, No 500 Lioufeng Road, Wufeng District, Taichung, 41354, Taiwan.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, China Medical University, No 91, Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors.forename: Hsun-Lang
authors.initials: HL
authors.lastname: Fang
authors.affiliation: Laboratory of Computational and System Biology, China Medical University, Taichung, No 91, Hsueh-Shih Road, Taichung, 40402, Taiwan.
authors.forename: Jhao-Guei
authors.initials: JG
authors.lastname: Yang
authors.affiliation: Department of Biomedical Informatics, Asia University, No 500 Lioufeng Road, Wufeng District, Taichung, 41354, Taiwan.
authors.forename: Yu-Chien
authors.initials: YC
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, China Medical University Hospital, No 2, Yu-Der Road, Taichung, 40431, Taiwan.
authors.forename: Huei-Yann
authors.initials: HY
authors.lastname: Tsai
mesh_terms: D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D039821:Monoterpenes / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D006027:Glycosides
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D018690:Excitatory Amino Acid Agonists; D005960:Glucosides; D039821:Monoterpenes; D009020:Morphine; D020319:Oligodeoxyribonucleotides, Antisense; D016194:Receptors, N-Methyl-D-Aspartate; C015423:peoniflorin; D006027:Glycosides
keywords: Antisense oligodeoxynucleotides; Excitatory amino acid agonists; High-dose morphine; NMDA receptor; NR2B; Nociceptive behavior; Paeoniflorin