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Nitric Oxide Synthase Inhibitors for the
Treatment of Chronic Tension-Type Headache
Ashina M.
Posted: April 2003  
Expert Opin Pharmacother 2002; 3:395-399

Chronic tension-type headache may be caused by prolonged painful input from pericranial myofascial tissues, such as tender points, resulting in central sensitization (increased excitability of neurons in the central nervous system). Animal studies have shown that sensitization of pain pathways may be caused by or associated with the activation of neuronal nitric oxide synthase and the generation of nitric oxide. Furthermore, it has been shown that nitric oxide synthase inhibitors reduce central sensitization in animal models of persistent pain. On the basis of this information, the analgesic effect of the nitric oxide synthase inhibitor L-N(G) methyl arginine hydrochloride was investigated. This drug significantly reduced headache and myofascial factors in patients with chronic tension-type headache. These studies show that nitric oxide plays a crucial role in the pathophysiology of tension-type headache. The analgesic effect of nitric oxide synthase inhibition in patients with chronic tension-type headache is probably due to a reduction in central sensitization at the level of the spinal dorsal horn, trigeminal nucleus or both. Furthermore, inhibition of nitric oxide synthase may become a novel principle in the future treatment of chronic headache.