ABSTRACT
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 µg/paw), reduced the allodynia when injected either 1 h before or 1 h after surgery. The effect of preoperative MK886 (160 µg/paw) against incisional allodynia had a magnitude apparently similar to that produced by postoperative MK886. Pre-, but not postoperative MK886 (80 µg/paw) reduced the allodynia but the effect was seen only at 6 h after surgery. In contrast, MK886 (40 µg/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.
Subject(s)
Animals , Male , Rats , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Indoles/administration & dosage , Indomethacin/administration & dosage , Lipoxygenase Inhibitors/administration & dosage , Pain, Postoperative/prevention & control , Disease Models, Animal , Drug Therapy, Combination , Rats, WistarABSTRACT
Volatile oil of C. deodara, administered orally at the doses of 50, 100 and 200 mg/kg body weight, significantly inhibited the pedal edema induced by compound 48/80 in rats. The oil significantly inhibited compound 48/80 induced degranulation of isolated rat peritoneal mast cells at concentrations ranging from 25-200 micrograms/ml. C. deodara wood oil also significantly inhibited the enzyme lipoxygenase at a concentration of 200 micrograms/ml. Thus, the anti-inflammatory activity of C. deodara wood oil could be attributed to its mast cell stabilizing activity and the inhibition of leukotriene synthesis.