Cyclooxygense-1 inhibition delays hypersensitivity to nerve injury

Despite the important role of both cyclooxygenase (COX) isoforms (i.e. COX-1 and COX-2) in maintenance of hypersensitivity following peripheral nerve injury, their role in the development of neuropathic pain is not clear. The present study was undertaken to determine the effect of COX inhibitors to address the potential role of COX isozymes in the development of neuropathic pain in rats after chronic nerve constriction injury. The paw withdrawal response to cold and mechanical stimulation was observed after every week for 4 weeks following nerve injury in rats. 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. However, administration of naproxen (10 or 30 mg/kg, i.p.) on day 7 reversed hypersensitivity but did not attenuate its development. Chronic administration of naproxen, but not rofecoxib, 2 h before and daily for 7 days after nerve injury, significantly and dose dependently attenuated and further delayed the development of hypersensitivity for 21 days following nerve injury. These results indicate that prolonged inhibition of COX-1 but not COX-2, following peripheral nerve injury could prevent the development of neuropathic pain.