Pharmacological characterization of carrageenan induced heat muscle hyperalgesia in rats using non-selective, preferential and selective COX-2 inhibitors

Abstract

BackgroundPrevious studies have shown that unilateral injection of carrageenan into the gastrocnemius muscle produces chronic thermal and mechanical hyperalgesia. AimIn the present study, we have characterized this model of muscoskeletal inflammatory pain, by evaluating the antihyperalgesic effects of selective and non-selective COX-2 inhibitors after systemic administration. Materials and methodsRats were injected with 3% carrageenan in the left gastrocnemius muscle and hyperalgesia to heat stimuli (measured as decreased withdrawal latency) to paws was assessed before and at varying times after injection, till end of 2nd week. Histological changes and the determination of prostaglandin E2 (PGE2) concentration were performed after the completion of drug treatment protocol. ResultsIntraperitoneal administrations of the selective COX-2 inhibitor celecoxib (7mg/kg) as well as preferential COX-2 inhibitors like nimisulide (5mg/kg) and aceclofenac (5mg/kg) attenuated hyperalgesia whereas non-COX-2 selective inhibitors like ibuprofen (40mg/kg) and indomethacin (10mg/kg) did not. Also the histopathological evidence suggests the beneficial effects of COX-2 selective inhibitors. The data suggest that selective inhibition of COX-2 produce good anti-inflammatory, analgesic and antihyperalgesic effects on Carrageenan-induced thermal inflammatory hyperalgesia. ConclusionIn the present carrageenan induced chronic pain model we have determined the role of analgesics in the reversal and inhibition of the state of chronic hyperalgesia. While considering the characterization of the present model our observations suggest the importance of a spinal COX-2 mechanism, a spinal action of systemically delivered drugs in the face of peripheral inflammation.