title: Cyclooxygenase-2 induction after oral surgery does not entirely account for analgesia after selective blockade of cyclooxygenase 2 in the preoperative period.
abstract: BACKGROUND
  The administration of selective cyclooxygenase-2 inhibitors before surgery is regarded as an innovative option to manage postoperative pain. This study was designed to (1) examine the efficacy of preoperative cyclooxygenase-2 blockade on postoperative oral pain and (2) compare pain intensity with prostaglandin E2 (PGE2) production and cyclooxygenase isoform (cyclooxygenase-1, cyclooxygenase-2) messenger RNA (mRNA) expression at the surgical site during the postoperative period.
  
  
  METHODS
  Sixty patients with impacted lower third molars were randomly allocated to three single-dose treatment groups--placebo, 50 mg rofecoxib, or 550 mg naproxen--1 h before extraction. Pain intensity was evaluated with categorical and visual analog scales every 30 min from 90 to 240 min after surgery. At these times, PGE2 production in the alveolar socket was also evaluated. Cyclooxygenase-1 and cyclooxygenase-2 mRNA expression was examined by reverse-transcription polymerase chain reaction in gingival specimens collected during tooth removal and 240 min after surgery.
  
  
  RESULTS
  Pain intensity and PGE2 production in the placebo group increased throughout the observation period. Naproxen prevented pain and decreased PGE2 release at all time points. Rofecoxib reduced PGE2 production versus placebo from 150 min onward, while inducing analgesia through the whole observation period. mRNA assay in gingival specimens collected at tooth extraction revealed cyclooxygenase-1 expression, whereas cyclooxygenase 2 was undetectable. At the end of observation, cyclooxygenase-1 mRNA expression was unchanged, whereas cyclooxygenase-2 mRNA was significantly induced.
  
  
  CONCLUSIONS
  This study indicates that preoperative administration of a selective cyclooxygenase-2 inhibitor ensures effective control of postoperative pain. It is suggested that the selective blockade of inducible cyclooxygenase 2 at the surgical site does not entirely account for the analgesic action occurring in the postoperative period.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fornai
authors.forename: Rocchina
authors.initials: R
authors.lastname: Colucci
authors.forename: Filippo
authors.initials: F
authors.lastname: Graziani
authors.forename: Silvia
authors.initials: S
authors.lastname: Cei
authors.forename: Luca
authors.initials: L
authors.lastname: Antonioli
authors.forename: Matteo
authors.initials: M
authors.lastname: Tonelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Vassalle
authors.forename: Corrado
authors.initials: C
authors.lastname: Blandizzi
authors.forename: Mario
authors.initials: M
authors.lastname: Gabriele
authors.forename: Mario
authors.initials: M
authors.lastname: Del Tacca
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000328:Adult; D051545:Cyclooxygenase 1 / Q000096:biosynthesis; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D015232:Dinoprostone / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007783:Lactones / Q000627:therapeutic use; D008297:Male; D017551:Microdialysis; D009288:Naproxen / Q000627:therapeutic use; D019647:Oral Surgical Procedures; D010149:Postoperative Pain / Q000188:drug therapy* / Q000201:enzymology*; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013450:Sulfones / Q000627:therapeutic use
chemical_list: D000199:Actins; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D011453:Prostaglandins; D012333:RNA, Messenger; D013450:Sulfones; C116926:rofecoxib; D009288:Naproxen; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone