Effect of pre-emptive analgesia on clinical parameters and tissue levels of TNF-alpha and IL-1beta in third molar surgery: a triple-blind, randomized, placebo-controlled study.

This study aimed to evaluate whether pre-emptive analgesia modifies the tissue expression of tumour necrosis factor alpha (TNF-alpha) and interleukin 1 beta (IL-1beta), and whether there is an association with postoperative surgical outcomes. A triple-blind, randomized, placebo-controlled study of patients undergoing mandibular third molar removal was performed. Volunteers were allocated randomly to receive etoricoxib 120 mg, ibuprofen 400 mg, or placebo 1h before surgery. Twenty-four surgical sites per group were required (95% confidence level and 80% statistical power). Pain scores differed significantly between groups (P<0.001). Etoricoxib and ibuprofen reduced pain scores compared to placebo (P<0.05). Pain scores peaked at 4h postoperative in the experimental groups, but at 2h postoperative in the placebo group (P<0.05). A significant reduction in TNF-alpha concentration from time 0' to time 30' was seen for ibuprofen (P=0.001) and etoricoxib (P=0.016). The ibuprofen group showed a significant reduction in IL-1beta levels from time 0' to time 30' (P=0.038). In conclusion, TNF-alpha and IL-1beta levels and the inflammatory events in third molar surgery were inversely associated with the degree of cyclooxygenase 2 selectivity of the non-steroidal anti-inflammatory drugs used pre-emptively. Patients given pre-emptive analgesia showed significant reductions in the clinical parameters pain, trismus, and oedema when compared to the placebo group.