Preoperative inhibition of cyclooxygenase-1 in the spinal cord reduces postoperative pain.

Intrathecal administration of cyclooxygenase (COX)-1, but not COX-2, specific inhibitors given on postoperative day 1 has analgesic effects in an incisional model of postoperative pain. We investigated the effects of preoperative administration of intrathecal COX inhibitors in this model. Fifteen minutes before surgery, rats received intrathecally the COX-1 preferring inhibitor, ketorolac, the specific COX-1 inhibitor, SC-560, the COX-2 inhibitor, NS-398, or vehicle. A 1-cm longitudinal incision was then made through skin, fascia, and muscles of the plantar aspect of a left paw in male rats. Withdrawal threshold to von Frey filaments was measured at 2 h, 4 h, and at intervals up to 5 days later. Ketorolac and SC-560 increased withdrawal threshold to mechanical stimulation, but NS-398 had no significant effect. These results suggest that COX-1 plays an important role in spinal cord pain processing and sensitization after surgery and that preoperative intrathecal administration of specific COX-1 inhibitors may be useful to treat postoperative pain.