It has been estimated that 9% of the US population suffers from moderate to severe non-cancer-related pain. Acute pain resulting from conditions such as headache, muscle spasms, dental problems or following surgery, affects 90 million Americans every year. Chronic pain is more troubling as it sparks a viscous cycle of clinical problems and often precipitates depression and/or life-style changes. Furthermore, establishing prolonged analgesia, free of serious side effects is a particularly challenging area of medicine. Estimates of the number of Americans suffering chronic pain range from 40-70 million. The total economic cost of pain is $100 (US) billion in the US alone and the estimated worldwide market for pain and inflammation treatments has been estimated as $18.7 (US) billion worldwide. It is therefore not surprising that the development of analgesics has represented a major pharmaceutical objective.  Migraine is a common pain related disorder affecting 4-16% of the global population although the prevalence is growing with an increase of almost 60% detected over the past decade. The migraine market has traditionally been a low growth, low value market, dominated by sales of aspirin/paracetamol and drugs in the ergotamine class, and suffering from poor awareness of the condition among patients and physicians. The market was revolutionized in the 1990s with the launch of Glaxo Wellcome's 5HT1D receptor agonist Imigran (sumatriptan), which was approved in the USA in 1992. The market sector has since increased by five fold to a current global value in excess of $2 billion as a result of increased incidence and treatment options. The activity in the market created by the triptans has drawn attention to migraine as a condition that can be treated with prescription drugs, and has also stimulated fresh research into the causes and mechanisms of migraine, as well as the development of treatments with fewer side effects. More recently, 5-HT7 receptor antagonists are starting to emerge as candidates for the treatment of migraine. Vascular and neural mechanisms have both been proposed to account for migraine and debate still exists as to which of these mechanisms may be of leading importance in the pathophysiology of the syndrome. 5-HT7 receptor antagonists are known to affect both the vasculature and pain pathways. In a recent study INSERM researchers have investigated the antinociceptive effects of sumatriptan and zolmitriptan, compared to dihydroergotamine in a rat model of trigeminal neuropathic pain. Sumatriptan at a clinically relevant dose led to a significant reduction of the mechanical allodynia-like behavior following chronic infraorbital nerve ligation. Zolmitriptan was more potent whereas whereas dihydroergotamine displayed much lower efficacy. These effects were attributed to 5-HT1B/1D receptor agonist activity. This is one of the first studies to show that 5-HT1B/1D receptor agonists are able to reduce trigeminal nociception in a model of chronic pain and supports the claim that both this therapeutic class and 5-HT7 receptor antagonists can target neural aspects of migraine

January, 2003

Adapted from Kayser et al Br J Pharmacol 2002 Dec;137(8):1287-97