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    ABSTRACT: In primary headaches, there is a clear association between the headache and the release of calcitonin gene-related peptide (CGRP) but not with any of the other neuronal messengers. The purpose of this review is to describe the role of CGRP in the intracranial circulation and to elucidate a possible role for a specific CGRP receptor antagonist in the treatment of primary headaches. Acute treatment with a 5-HT(1B/1D) agonist (triptan) results in alleviation of the headache and normalization of the cranial venous CGRP levels, in part due to a presynaptic inhibitory effect on sensory nerves. The central role of CGRP in migraine and cluster headache pathophysiology has led to the search for small molecule CGRP antagonists with few cardiovascular side-effects. The initial pharmacological profile of such a group of compounds has recently been disclosed. One of these compounds has been found to be efficacious in the relief of acute attacks of migraine.
    Cephalalgia 09/2004; 24(8):611-22. DOI:10.1111/j.1468-2982.2003.00719.x · 4.89 Impact Factor
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    ABSTRACT: For many migraine patients, triptan therapy provides complete pain relief in some attacks but not in others. Here, we tested whether the success of triptan therapy is hindered in the presence of cutaneous allodynia (pain resulting from a nonnoxious stimulus to normal skin), a phenomenon we previously described develop gradually during the course of the migraine attack in more than 70% of patients. We studied migraine patients repeatedly on three visits to the clinic: in the absence of migraine (baseline), within the first hour of one attack, or at 4 hours from onset of another attack. Presence or absence of allodynia was determined based on differences between migraine and baseline pain thresholds to mechanical and thermal stimulation of periorbital skin. In 31 patients, we studied 34 migraine attacks that were associated with allodynia at the time of triptan treatment and 27 attacks that were not. Within 2 hours of triptan treatment, patients were rendered pain-free in 5 of 34 (15%) of allodynic attacks versus 25 of 27 (93%) of nonallodynic attacks. Treating migraine attacks 1 hour (early) or 4 hours (late) after the onset of pain was equally ineffective in inducing a pain-free state in the presence of allodynia, and equally effective in the absence of allodynia. For patients susceptible to allodynia during the attack, triptan therapy was by far more likely to provide complete pain relief if administered before rather than after the establishment of cutaneous allodynia. Patients who never developed allodynia were highly likely to be rendered pain-free by triptan therapy anytime after the onset of pain. We conclude that the probability of consistent pain-free outcome increases drastically if triptan therapy is vigilantly timed to precede any signs of cutaneous allodynia.
    Annals of Neurology 01/2004; 55(1):19-26. DOI:10.1002/ana.10786 · 9.98 Impact Factor
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    Headache The Journal of Head and Face Pain 04/2012; 52(1). DOI:10.1111/j.1526-4610.2011.02083.x · 2.71 Impact Factor
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