The current study showed that, 15 minutes before surgery, intrathecal administration of a COX-1 preferring inhibitor, ketorolac, and a selective COX-1 inhibitor, SC-560, reduced the hypersensitivity induced by paw incision but a COX-2 inhibitor, NS-398, had no significant effect. These results support our previous observation that spinal COX-1 plays an important role in postoperative pain processes (4). In contrast, other studies have shown that inhibition of spinal COX-1 by SC-560 has no effect on intrathecal substance P-induced thermal hyperalgesia (9). In addition, intrathecal injection of the COX-2 inhibitor, NS-398, prevents hypersensitivity induced by intrathecal NMDA or AMPA (17) and attenuates thermal hyperalgesia induced by paw inflammation from carrageenan (10). These results underscore the unique pharmacology of postoperative pain.
We do not argue that COX-2 inhibitors are useless for treating postoperative pain. Actually, selective COX-2 inhibitors, systemically administrated, have been shown to relieve postoperative pain in humans (19) and to reduce paw incision-induced mechanical hypersensitivity in rats (20,21). Because surgical tissue injury results in the peripheral synthesis and release of many inflammatory mediators, including PGs, and because these mediators sensitize peripheral nociceptors by altering their firing threshold and sometimes causing direct stimulation (22), the COX-2 inhibitors are considered to achieve analgesic effects by inhibiting COX-2 enzyme in the peripheral tissue and thus reduce PG synthesis. Yet our results argue that the COX-1 enzyme is also important in the underlining mechanisms of postoperative pain.
In conclusion, COX-1 preferring and selective inhibitors, when administrated preoperatively, reduce paw incision-induced mechanical hypersensitivity, but the COX-2 inhibitors lack efficacy. These data support the notion that COX-1 may play an important role in pain processing and sensitization in spinal cord after peripheral surgery and that preoperative intrathecal COX-1 inhibitors may be useful for treating postoperative pain.
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