Role of Spinal Cyclooxygenase in Human Postoperative and Chronic Pain

Background: Nonsteroidal antiinflammatory drugs are commonly used to treat postoperative and chronic pain. Animal studies suggest that these drugs act, in part, by blocking prostaglandin production in the spinal cord. The authors tested intrathecal ketorolac in patients with chronic or postoperative pain. Methods: After approval of the institutional review board and the Food and Drug Administration, three clinical studies were performed. First, 15 patients receiving chronic intrathecal morphine received 0.5-2.0 mg of intrathecal ketorolac. Second, 12 patients receiving chronic intrathecal morphine received, in a double-blinded, randomized, cross-over design, intrathecal saline or 2.0 mg of ketorolac, with pain intensity as the primary outcome measure. Third, 30 patients undergoing total vaginal hysterectomy received, in a double-blinded, randomized, controlled design, intrathecal saline or 2.0 mg of ketorolac, with bupivacaine with time to first morphine dose after surgery as the primary outcome measure. Results: Patients with chronic pain had many symptoms before intrathecal injection, without worsening of these symptoms from ketorolac. Pain intensity was reduced by intrathecal ketorolac, but this did not differ from placebo. In the first study, pain was reduced by intrathecal ketorolac in patients with high cerebrospinal fluid prostaglandin E2 concentrations but not in those with normal concentrations. Intrathecal ketorolac did not alter time to first morphine after surgery. Conclusions: Intrathecal ketorolac did not relieve chronic pain or extend anesthesia or analgesia from intrathecal bupivacaine administered at the beginning of surgery. Under the conditions of these studies, it seems that spinal cylcooxygenase activity does not contribute to chronic or postoperative pain.