Modulatory role of nitric oxide and cyclooxygenase enzyme pathway in LPS-mediated hyperalgesia

Nitric oxide (NO) is a free radical, is known to play an important role in many physiological and pathological processes. Evidence suggests that NO participates in the pathogenesis of inflammatory reactions. It has been reported that exposure of tissues to endotoxin (LPS) leads to induction of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In the present study we have investigated the role of iNOS in LPS-mediated hyperalgesia in mice and the regulatory role between prostanoids in vivo using L-NAME, a non-specific nitric oxide synthase inhibitor, and spirulina purified protein (SPP) containing C-phycocyanin, NS-398 and rofecoxib, COX-2 selective inhibitor in various nociceptive assays. Acute administration of LPS (50 μg/mouse, i.p. or 10 μg/paw, i.pl.) significantly demonstrated hyperalgesia in chemical, thermal and mechanical nociception in mice, respectively. Treatments of mice with L-NAME (5-20 mg/kg, i.p. or 10-40 μg/paw, i.pl.) significantly reversed the LPS-mediated hyperalgesia in peripheral or central nociception in mice. Treatment with SPP (50 and 100 mg/kg, p.o.), NS398 (10 mg/kg, p.o.) and rofecoxib (10 mg/kg, p.o.), significantly exhibited antihyperalgesic effect in chemical hyperalgesia. These COX-2 inhibitors significantly potentiated the L-NAME reversal of LPS-mediated hyperalgesia. It is concluded that iNOS plays a significant role in LPS-mediated hyperalgesia and simultaneous inhibition of COX-2 enzyme leads to modulatory effect between NO and prostanoids.