The amplification of
pain long after the initial stimulus may be avoided if the treatment of
pain is introduced before its initiation. However, conflicting evidence exists about the efficacy of such preemptive
analgesia for the management of
postoperative pain. This study compares the efficacy of intraplantar administration of
indomethacin (a non-selective inhibitor of
cyclooxygenase) and
MK886 (an inhibitor of
5-lipoxygenase-activating protein), separately or in combination to produce preemptive
analgesia in a model of surgical incisional
pain in male Wistar rats. All incised rats (5 to 6 rats per group) had
allodynia at 2, 6, and 24 h after surgery as evaluated using von Frey filaments.
MK886, but not
indomethacin (50 to 200 microg/paw), reduced the
allodynia when injected either 1 h before or 1 h after surgery. The effect of preoperative
MK886 (160 microg/paw) against incisional
allodynia had a magnitude apparently similar to that produced by postoperative
MK886. Pre-, but not postoperative
MK886 (80 microg/paw) reduced the
allodynia but the effect was seen only at 6 h after surgery. In contrast,
MK886 (40 microg/paw) intensified the
allodynia observed 2 h after the incision either injected before or after surgery.
MK886 or
indomethacin alone did not provide preemptive
analgesia in the model of incisional
pain. In contrast, the combination of
MK886 with
indomethacin reduced the
allodynia more effectively when used before than after surgery, thus fulfilling the criteria for preemptive
analgesia. In conclusion, preoperative inhibition of the local generation of both
prostaglandins and
leukotrienes by
surgical incision may be an alternative to provide preemptive
analgesia.