Involvement of inflammation in severe post-operative pain demonstrated by pre-surgical and post-surgical treatment with piroxicam and ketorolac

Abstract

Abstract Objectives Post-operative pain is considered to involve inflammation caused by tissue injury. However, the mechanism and timing of the involvement of inflammation in the post-operative pain remain complicated because they can vary among different types of surgery. In this study a rat incision model was used to investigate how inflammation induced by cyclooxygenases (COXs) is involved in severe post-operative pain. Methods Longitudinal incision with a length of 1 cm was made through skin and fascia on the right hind paw of rats, starting 0.5 cm from the edge of the heel and extending towards the toes. Allodynia was evaluated using the von Frey hair test and its degree was recorded as the paw withdrawal threshold (PWT). Two non-steroidal anti-inflammatory drugs (NSAIDs), piroxicam and ketorolac, were given to rats after or before surgery, and the effects of the drugs on allodynia induced by the hind paw incision were examined. Key findings The PWT reduction reached a sub-maximal level at 3 h, a maximal level at one day after the surgery and lasted for more than 8 days, with the parallel development of inflammation (characterized by cell infiltration and oedema). Treatment with morphine (1 mg/kg, s.c.) at one day after the surgery showed a significant anti-allodynic effect. Treatment with either piroxicam (10 mg/kg, p.o.) or ketorolac (10 mg/kg, p.o.) at one day after the surgery did not exhibit significant anti-allodynic effect, whereas pre-surgical treatment with each drug showed significant anti-allodynic effects at 3 h after surgery. Conclusions These findings suggest the involvement of cyclooxygenases in evoking pain that occurs in the immediate post-operative period, and that an initial suppression of rapid inflammation by treatment with NSAIDs before major surgery plays an important role in the management of severe post-operative pain.