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Effect of a selective COX‐2 inhibitor in the development of central sensitization in the oral surgery model
Author(s) -
Picco C. C.,
Lee Y.,
Chuang B. P.,
Gordon S. M.,
Brahim J. S.,
Dionne R. A.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.014
Subject(s) - rofecoxib , medicine , anesthesia , sensitization , placebo , nociception , ketorolac , lidocaine , prostaglandin , microdialysis , prostaglandin e2 , prostanoid , clinical pharmacology , pharmacology , local anesthetic , hyperalgesia , cyclooxygenase , analgesic , central nervous system , receptor , chemistry , immunology , biochemistry , alternative medicine , pathology , enzyme
Nociceptive input from surgical insult and postoperative inflammation contribute to the development of central sensitization, yet their relative contributions have not been evaluated. COX‐1 and ‐2 catalyze prostaglandin synthesis, with COX‐1 being primarily responsible for PGE2 production over the first 1–2 hours with COX‐2 regulation at later time points. This study evaluated the effect of COX‐2 mediated prostanoid production to nociceptive input contributing to the development of central sensitization in the oral surgery model with either 50 mg rofecoxib or placebo administered preoperatively and lidocaine or long‐acting bupivicaine used for local anesthesia. Microdialysis was used to collect submucosal perfusate from the surgical site for four hours postoperatively and pain report recorded concurrently. Both rofecoxib and bupivicaine suppressed pain in the immediate postoperative period independently and additively. PGE2 levels were significantly suppressed by rofecoxib as compared to placebo across the last two hours of the postoperative period (p < 0.05). TXB2 levels did not differ significantly between groups during the postoperative period. The local anesthetic did not have any effect on PGE2 or TXB2 levels. The suppression of PGE2 during the later time points suggests that inhibition of cytokine mediated postoperative inflammation limits the development of sensitization following surgery. Clinical Pharmacology & Therapeutics (2004) 75 , P4–P4; doi: 10.1016/j.clpt.2003.11.014