– The group IVA phospholipase A2 (PLA2), known as calcium-dependent cytosolic PLA2 (cPLA2), selectively releases arachidonic acid from membrane phospholipids, playing a central role in initiating the synthesis of prostaglandins and leukotrienes. AX 048 is a potent group IVA cPLA2 inhibitor that demonstrates 50% inhibition of the enzyme at a mole fraction (XI(50)) of 0.022. Pretreatment with AX 048 (ED50 = 1.2 mg/kg) dose-dependently reduces thermal hyperalgesia evoked by carrageenan injection of rat hind paw. At concentrations as high as 30 μM, AX 048 does not inhibit COX activity or interfere with central cannabinoid receptor signaling.