title: [Synergistic analgesic effect of choline and parecoxib sodium in mice and the mechanism].
abstract: OBJECTIVE
  To investigate the synergistic analgesic effect of choline and parecoxib sodium and study its mechanism.
  
  
  METHODS
  In male Kunming mice with acetic acid-induced writhing, the ED50of choline and parecoxib sodium (administered via the tail vein at 2 h and 30 min before modeling, respectively) and their combined use were determined. In saline (control) group, ED50choline (C) group, ED50parecoxib sodium (P) group, and 1/2ED50choline and parecoxib sodium (1/2[C+P]) group, blood samples were collected from the eyeball 10 min after intraperitoneal administration of acetic acid to detect the levels of IL-1, TNF-α, PGE2, NF-κB, and I-κB levels using ELISA kits.
  
  
  RESULTS
  In the acetic acid-induced writhing model, the ED50of choline and parecoxib sodium was 8.64 and 6.33 mg/kg, and when combined, their ED50 was 2.13 and 1.56 mg/kg, respectively. The isobolograms of parecoxib sodium and choline showed that the measured ED50of the two drugs combined was below the theoretical ED50value (P<0.05) with a combination index (CI) of <0.9. Compared with the control group, C group, P group, and 1/2 (C+P) group all showed significantly lowered IL-1 and TNF-α levels (P<0.05), especially in 1/2 (C+P) group (P<0.05). PGE2 level was significantly lower in P group and 1/2 (C+P) group compared with the control group (P<0.05). NF-κB and I-κB levels were significantly lowered in C, P, and 1/2 (C+P) groups (P<0.05), and the reduction was the most obvious in 1/2 (C+P) group (P<0.05).
  
  
  CONCLUSIONS
  Choline and parecoxib sodium has a synergistic analgesic effect, and their interactions may involve the in vivo expression of NF-κB.
authors.affiliation: Anesthesia and Operation Center, General Hospital of PLA, Beijing 100853, China.E-mail: 15326711967@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Zhang
authors.forename: Ze-Guo
authors.initials: ZG
authors.lastname: Feng
authors.forename: Ru-Huan
authors.initials: RH
authors.lastname: Wang
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: DU
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002794:Choline / Q000494:pharmacology*; D004357:Drug Synergism; D020672:I-kappa B Proteins / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000700:Analgesics; D020672:I-kappa B Proteins; D007375:Interleukin-1; D007555:Isoxazoles; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C409945:parecoxib; D002794:Choline