Post-operative pain and
inflammation are frequently managed with non-steroidal anti-inflammatory drugs (
NSAIDs). Despite the prevalence of their use, however, relatively little is known about in vivo tissue concentrations of inflammatory mediators at the site of tissue injury and their modulation by
NSAIDs. This study compares the effect of
oral administration of the
NSAID flurbiprofen, to placebo, on tissue levels of immunoreactive
prostaglandin E2 (iPGE2),
leukotriene B4 (iLTB4), and (S)-
flurbiprofen within the
surgical wound using implanted microdialysis probes in the dental impaction
pain model. Twenty-four healthy patients in need of extraction of partial to complete bony mandibular third molars were recruited for this randomized, double-blind, placebo-controlled study. Following pre-operative administration of N2O/O2,
midazolam i.v., and regional block
anesthesia with 3%
mepivacaine, each patient underwent surgical removal of their impacted third molars. Immediately following completion of the surgery, two semi-permeable microdialysis probes (3 kDa molecular weight cut-off) were implanted into each mandibular surgical site. Patients were taken to a recovery room and microdialysis samples and patient
pain reports (visual analog scale, VAS) were collected at 30 min intervals for 4 h. Patients randomly received either
flurbiprofen (200 mg orally) or placebo at the onset of
post-operative pain.
Dialysate samples were collected, frozen, and later assayed for iPGE2, iLTB4, and (S)-
flurbiprofen levels. Results of this study show that
flurbiprofen decreased
post-operative pain by approximately 70% compared to placebo-treated patients (P < 0.001). During the 4 h post-operative timecourse of this study,
flurbiprofen treatment significantly reduced peak tissue levels of iPGE2 (9.2 +/- 2.6 vs. 0.4 +/- 0.15 nM; P < 0.001), without having a significant effect on peak tissue levels of iLTB4 (2.5 +/- 1.4 vs. 1.49 +/- 0.86 nM) compared to placebo treatment. Levels of (S)-
flurbiprofen significantly increased within the
surgical wound exceeding therapeutic levels by 60 min after administration.
Flurbiprofen is able to significantly suppress the local production of iPGE2 and provide significant
analgesic efficacy without altering iLTB4 tissue levels in this model of acute post-operative inflammatory
pain. These data indicate that
NSAIDs selectively alter
eicosanoid levels within
surgical wound and evoke
analgesia at time points coincident with elevated
wound levels of the
drug. The combined use of microdialysis probes in awake patients who provide simultaneous
pain reports may offer insight into peripheral mechanisms of inflammatory mediator release and
pain.