L-arginine is the natural substrate for NOS and can increase NO levels in certain tissues. Although it antagonizes the action of the NOS inhibitors, studies have shown that it produces a moderate degree of analgesia when administered alone. In fact, studies in horses suggest that substances that donate or increase NO may relieve pain. Other studies have shown that a 10% intravenous infusion of L-arginine caused vasodilation and improved the circulation in hooves of ponies with grass-induced acute laminitis. Topical application of nitroglycerine, a potent vasodilator and NO donor, was reported to reduce the bounding pulses, decrease lameness and lower blood pressure in the laminitic ponies. These data suggest that despite the fact that L-arginine and nitroglycerine produce NO (which contributes to pain), their ability to vasodilate, improve pedal circulation and ultimately relieve pain may be more important.  Certainly, agents that affect the production of NO are worthy of further study in horses with laminitis and other inflammatory conditions.