Differential effects of naproxen and rofecoxib on the development of hypersensitivity following nerve injury in rats

The present study was undertaken to determine the effects of cyclooxygenase (COX) inhibitors on the development of neuropathic pain in rats following chronic constriction injury (CCI). A single intraperitoneal administration of naproxen, a nonselective COX inhibitor (10 or 30 mg/kg), or rofecoxib, a selective COX-2 inhibitor (3 or 10 mg/kg) 2 h before nerve injury did not attenuate the development of neuropathic state for 28 days. However, the administration of naproxen [10 or 30 mg/kg, intraperitonelly (i.p.)], but not rofecoxib (3 or 10 mg/kg, i.p.), on day 7 attenuated hypersensitivity but did not alter its development for 28 days. Furthermore, naproxen significantly reduced hyperalgesia and allodynia for 4 h, but the efficacy was not observed 24 h after the treatment, whereas rofecoxib failed to modify the hypersensitivity following perineural (p.n.) or intrathecal (i.t.) administration on day 7. Chronic administration of naproxen (3, 10 or 30 mg/kg), but not rofecoxib (1, 3 or 10 mg/kg), 2 h before, daily for 7 days, after nerve injury significantly attenuated and further delayed the development of hypersensitivity for 21 days following nerve injury. These results suggest that the development of hypersensitivity in the CCI model is not COX-2 dependent and that the chronic administration of naproxen started early before peripheral nerve injury could attenuate the development of hypersensitivity. (C) 2004 Elsevier Inc. All rights reserved.