Spinal antinociceptive effect of epidural nonsteroidal antiinflammatory drugs on nitric oxide-induced hyperalgesia in rats

Background Nonsteroidal antiinflammatory: drugs (NSAIDs) suppress various h yperalgesia perhaps via inhibition of cyclooxygenase activity at the spinal cord, The present study aimed to examine whether epidural application of N SAIDs affects hyperalgesia induced by nitric oxide. Methods: The authors studied the antinociceptive effects of epidurally admi nistered NSAIDs in rats with a chronically indwelling epidural catheter by three hyperalgesic models, including nitric oxide-induced hyperalgesia by n itroglycerin (10 mu g) or l-arginine (100 mu g), and the biphasic response in the formalin test. Results: Epidural, but not systemic, nitroglycerin induced hyperalgesia tha t was completely blocked by methylene blue but not by N-omega-nitro-L-argin ine methyl ester (L-NAME). Epidural l-arginine, but not d-arginine, also in duced hyperalgesia that mas completely blocked by L-NAME. Epidural S(+)ibup rofen (100-1,000 mu g) suppressed the nitroglycerin- and l-arginine-induced thermal hyperalgesia and also the second phase response in the formalin te st. Neither systemic S(+)ibuprofen nor epidural R(-)ibuprofen suppressed th e hyperalgesia. Epidural indomethacin (10-100 mu g) or diclofenac (10-1,000 mu g) dose-dependently suppressed nitroglycerin-induced thermal hyperalges ia, The order of potency for this suppression (ID50 in mu g) mas indomethac in is approximately equal to diclofenac > S(+)ibuprofen much greater than R (-)ibuprofen. Conclusions: The antinociceptive action of epidurally administered NSAIDs c ould be the result of suppression of spinal sensitization, perhaps induced with nitric oxide in the spinal cord. The ID50 values for epidural indometh acin, diclofenac, and S(+)ibuprofen were about 10 times higher than those r eported in other studies for intrathecal NSAIDs in hyperalgesia models.