Effect of pre-emptive analgesia on clinical parameters and tissue levels of TNF-α and IL-1ß 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-α) and interleukin 1 beta (IL-1ß), 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-α 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-1ß levels from time 0' to time 30' (P=0.038). In conclusion, TNF-α and IL-1ß 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.

Tephrosia toxicaria†Pers. reduces temporomandibular joint inflammatory hypernociception: the involvement of the HO-1 pathway.

BACKGROUND: We investigated both the efficacy and the sub-chronic toxicity of Tephrosia toxicaria Pers. in the zymosan-induced temporomandibular joint (TMJ) inflammatory hypernociception in rats evaluating the possible role of heme oxygenase-1 (HO-1). METHODS: Rats were pretreated with T. toxicaria (0.2, 2.0 or 20 mg/kg) 60 min before the intra-articular injection of zymosan (2 mg, 40 µL) in the left TMJ. In another series of experiments, rats were treated with ZnPP-IX (3 mg/kg), a specific HO-1 inhibitor, before T. toxicaria (20 mg/kg). Von Frey test was used to evaluate inflammatory hypernociception (g) 4 h after zymosan injection. Six hours after zymosan injection, the synovial lavage was collected for total cell count and myeloperoxidase (MPO) activity, and joint tissue for histopathological analysis and immunohistochemistry for HO-1. To evaluate the sub-chronic toxicity, mice received T. toxicaria (20 mg/kg) or saline once a day for 14 days to analyse body mass, organ weight and biochemical parameters. RESULTS: T. toxicaria partially reversed the zymosan-induced head withdrawal threshold, the number of cells and the MPO activity. T. toxicaria reduced the inflammatory cell influx in the synovial membrane. TMJ immunohistochemical analyses treated with T. toxicaria showed increased HO-1 expression. These effects of T. toxicaria were not observed in the presence of ZnPP-IX. T. toxicaria treatment for 14 days did not show significant signs of toxicity when administrated to mice. CONCLUSIONS: T. toxicaria did not produce any signs of toxicity and effectively decreased zymosan-induced TMJ inflammatory hypernociception dependent, at least in part, upon the HO-1 pathway integrity.