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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The specific cause of migraine headache remains unknown. Current theories suggest that the initiation of a migraine attack involves a primary CNS dysfunction with subsequent activation of the trigeminovascular system. Studies in patients have revealed a clear association between headache and the release of the neuropeptide calcitonin gene-related peptide, probably from C fibres. In cluster headache and in a case of chronic paroxysmal headache there was in addition release of the parasympathetic neuropeptide vasoactive intestinal peptide, which was associated with headache, nasal congestion and rhinorrhea. Triptan administration, activating the 5-HT(1B/1D) receptors, caused the headache to subside and the neuropeptide release to normalise. These data suggest the involvement of sensory and parasympathetic mechanisms in the pathophysiology of primary headaches.
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PMID:Aspects on the pathophysiology of migraine and cluster headache. 1155 22

The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute migraine drugs. Soon, seven different triptans will be clinically available at 13 different oral doses, making evidence-based selection guidelines necessary. Triptan trials have similar designs, facilitating meta-analysis. We wished to provide an evidence-based foundation for using triptans in clinical practice, and to review the methodological issues surrounding triptan trials. We asked pharmaceutical companies and the principal investigators of company-independent trials for the 'raw patient data' of all double-blind, randomized, controlled, clinical trials with oral triptans in migraine. All data were cross-checked with published or presented data. We calculated summary estimates across studies for important efficacy and tolerability parameters, and compared these with those from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials, 53 (12 not yet published) involving 24089 patients met the criteria for inclusion. Mean results (and 95% confidence intervals) for sumatriptan 100 mg, the first available and most widely prescribed oral triptan, are 59% (57-60) for 2 h headache response (improvement from moderate or severe to mild or no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained pain free (pain free by 2 h and no headache recurrence or use of rescue medication 2-24 h post-dose), and 67% (63-70) for consistency (response in at least two out of three treated attacks); placebo-subtracted proportions for patients with at least one adverse event (AE) are 13% (8-18), for at least one central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7). Compared with these data: rizatriptan 10 mg shows better efficacy and consistency, and similar tolerability; eletriptan 80 mg shows better efficacy, similar consistency, but lower tolerability; almotriptan 12.5 mg shows similar efficacy at 2 h but better sustained pain-free response, consistency, and tolerability; sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show lower efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 40 mg, and rizatriptan 5 mg show very similar results. The results of the 22 trials that directly compared triptans show the same overall pattern. We received no data on frovatriptan, but publicly available data suggest substantially lower efficacy. The major methodological issues involve the choice of the primary endpoint, consistency over multiple attacks, how to evaluate headache recurrence, use of placebo-subtracted proportions to control for across-study differences, and the difference between tolerability and safety. In addition, there are a number of methodological issues specific for direct comparator trials, including encapsulation and patient selection. At marketed doses, all oral triptans are effective and well tolerated. Differences among them are in general relatively small, but clinically relevant for individual patients. Rizatriptan 10 mg, eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of consistent success. Sumatriptan features the longest clinical experience and the widest range of formulations. All triptans are contra-indicated in the presence of cardiovascular disease.
Cephalalgia 2002 Oct
PMID:Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. 1526 60

Headache disorders represent a serious threat to the sufferer's quality of life and normal day-to-day functioning. Headache generates a substantial disability burden, being classified among the major public health disorders. There is no doubt that the emergence of the triptan class in the early 1990s dramatically advanced the treatment of migraine and has changed the perspective of the migraine sufferer with respect to the treatment. Triptan therapies for migraine relief have been proven to be safe and efficacious in clinical trials. Nevertheless, endpoint-based clinical trials are focused more on specific measures of efficacy and tolerability (e.g., relief, response and adverse event rates), and less on the patient's feelings and quality of life. For instance, in the U.S. only 29% of migraine sufferers are very satisfied with their usual treatment. The principal reasons for their dissatisfaction with therapy are as follows: pain relief takes too long (87%), treatment does not relieve all the pain (87%), treatment does not always work (85%), headache comes back (71%), and too many side effects (35%). Thus, this work is focused on patients' perspectives on migraine therapies attempting to establish their needs and to find better treatment possibilities for restoring patients' overall functionality.
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PMID:Patient-focused migraine management: establishing needs. 1507 14

Triptan therapy results in good relief of headache in 68% of the patients. For many of the patients with migraine, triptan provides complete pain relief in some attacks but not in others. A recent theory proposes that allodynia (pain sensitization) develops in the brain during migraine to increase the intensity of headache significantly. The presence of cutaneous allodynia, an exaggerated painful sensation resulting from a no noxious stimulus to normal skin, is reported in more than 70% of the patients. In our prospective study with 41 patients with migraine, 54.2% presented with skin allodynia. Triptan was effective in 77% of the patients without allodynia which was higher than the base line efficacy rate of 68% in all the patients. Our data support the hypothesis that the development and maintenance of cutaneous allodynia is propelled by sensitization of central trigeminal nucleus. It is suggested that the pain-free outcome increases drastically if triptan therapy is given before the phenomenon of allodynia develops during the attacks of migraine.
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PMID:[Mechanism based prevention and treatment of migraine]. 1565 Dec 98

Primary headaches such as migraine and cluster headache are neurovascular disorders. Migraine is a painful, incapacitating disease that affects a large portion of the adult population with a substantial economic burden on society. The disorder is characterised by recurrent unilateral headaches, usually accompanied by nausea, vomiting, photophobia and/or phonophobia. A number of hypothesis have emerged to explain the specific causes of migraine. Current theories suggest that the initiation of a migraine attack involves a primary central nervous system (CNS) event. It has been suggested that a mutation in a calcium gene channel renders the individual more sensitive to environmental factors, resulting in a wave of cortical spreading depression when the attack is initiated. Genetically, migraine is a complex familial disorder in which the severity and the susceptibility of individuals are most likely governed by several genes that vary between families. Genom wide scans have been performed in migraine with susceptibility regions on several chromosomes some are associated with altered calcium channel function. With positron emission tomography (PET), a migraine active region has been pointed out in the brainstem. In cluster headache, PET studies have implicated a specific active locus in the posterior hypothalamus. Both migraine and cluster headache involve activation of the trigeminovascular system. In support, there is a clear association between the head pain and the release of the neuropeptide calcitonin gene-related peptide (CGRP) from the trigeminovascular system. In cluster headache there is, in addition, release of the parasympathetic neuropeptide vasoactive intestinal peptide (VIP) that is coupled to facial vasomotor symptoms. Triptan administration, activating the 5-HT(1B/1D) receptors, causes the headache to subside and the levels of neuropeptides to normalise, in part through presynaptic inhibition of the cranial sensory nerves. These data suggest a central role for sensory and parasympathetic mechanisms in the pathophysiology of primary headaches. The positive clinical trial with a CGRP receptor antagonist offers a new promising way of treatment.
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PMID:Neurobiology in primary headaches. 1591 51

In childhood and adolescence, migraine is the main primary headache. This diagnosis is largely underestimated and misdiagnosed in the pediatric population. Because of the lack of specific biologic markers, specific investigation tools or brain imaging techniques, these clinical entities are too often considered to be a psychological illness. Migraine is a severe headache evolving by stereotyped attacks associated with marked digestive symptoms (nausea and vomiting); throbbing pain and sensitivity to sound or light are common symptoms; the attack is sometimes preceded by a visual or sensory aura. During attacks, pain intensity is severe; most of the children have to lie down. Abdominal pain is frequently associated, rest brings relief and sleep often ends the attack. The prevalence of migraine varies between 5 percent and 10 percent in childhood. In children, the duration of the headache is quite often shorter than in adults; it is more often frontal and bilateral (2/3 of cases) than one-sided. Migraine is a disabling illness: children with migraine miss more school days in a school year than their matched controls. Migraine episodes are frequently triggered by several factors: emotional stress (school pressure, vexation, excitement: upset), hypoglycemia, lack of sleep or excess (week end migraine), sensorial stimulation (loud noise, bright light, strong odor, heat or cold...), sympathetic stimulation (sports, physical exercise). Treatment must be given early at onset of attacks; oral ibuprofen (10 mg/kg) is recommended. If the oral route in not available because of nausea or vomiting, the rectal or nasal routes can be used. Triptan can be prescribed (body weight above 30 kg) when NSAID (prescribed at right dose and time) fail to abort the attack. Non-drug treatments (relaxation training, self hypnosis, biofeedback) have shown to have good efficacy as prophylactic measures. Daily prophylactic drug treatments are prescribed in second line after failure of non-drug treatment.
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PMID:[Migraine in childhood]. 1614 60

An understanding of the pathophysiology and pharmacology of migraine has been driven by astute clinical observations, elegant experimental medicine studies and importantly by the introduction of highly effective selective anti-migraine agents such as the Triptan 5-HT(1B/1D) agonists. New investigational migraine therapies such CGRP antagonists target key components of the trigeminal sensory neuroinflammatory response and show promise for the future. Cutting edge molecular profiling studies looking at gene expression during chronic pain are now being used to reveal the cell biology of pain and new potential therapeutic targets. Translational neuroimaging research can link the laboratory and the clinic and is now being used to help understand the neural systems biology of migraine. Research into migraine has generated sophisticated hypotheses that encompass primary CNS dysfunction, trigeminovascular activation, pain perception and activation of associated neural circuits involved in affective functions providing a rich framework within which to design and test future migraine treatment strategies.
Headache 2007 Apr
PMID:New migraine and pain research. 1742 8

Population-based data on migraine incidence and comorbidity are scarce. We therefore aimed to quantify incidence rates and comorbidity of diagnosed migraine and health resource utilization (HRU) in migraineurs in the UK primary care setting. We conducted a follow-up study with a nested case-control analysis on the General Practice Research Database. The study encompassed 51,688 patients with a first-time diagnosis of migraine between 1994 and 2001, and the same number of matched controls. The migraine incidence rate was 3.69 (95% confidence interval 3.66, 3.73) cases per 1000 person-years. It was around 2.5 times higher in women. Most chronic diseases were slightly more prevalent in migraineurs than in controls. Triptan users had higher health resource utilization than other migraineurs. This study shows that migraine is a common diagnosis in general practice and associated with a high prevalence of comorbidity. The increased HRU in triptan users suggests greater migraine severity.
Cephalalgia 2008 Jan
PMID:Migraine incidence, comorbidity and health resource utilization in the UK. 1798 74

Menstrual migraine (MM) is either pure, if attacks are limited solely during the perimenstrual window (PMW), or menstrually related (MRM), if two of three PMWs are associated with attacks with additional migraine events outside the PMW. Acute migraine specific therapy is equally effective in MM and non-MM. Although the International Classification of Headache Disorders-II classifies MM without aura, data suggest this needs revision. The studies on extended-cycle oral contraceptives suggest benefits for headache-prone individuals. Triptan mini-prophylaxis outcomes are positive, but a conclusion of "minimal net benefit compared to placebo" is not entirely unwarranted. In a 2008 evidence-based review, grade B recommendations exist for sumatriptan (50 and 100 mg), mefenamic acid (500 mg), and riza-triptan (10 mg) for the acute treatment of MRM. For the preventive mini-prophylactic treatment of MRM, grade B recommendations are provided for transcutaneous estrogen (1.5 mg), frovatriptan (2.5 mg twice daily), and naratriptan (1 mg twice daily).
Curr Pain Headache Rep 2009 Feb
PMID:Clinical aspects of perimenstrual headaches. 1912 76

Migraine is a common neurological disorder often treated with triptans. Triptan overuse can lead to increased frequency of headache in some patients, a phenomenon termed medication overuse headache. Previous preclinical studies have demonstrated that repeated or sustained triptan administration for several days can elicit persistent neural adaptations in trigeminal ganglion cells innervating the dura, prominently characterized by increased labelling of neuronal profiles for calcitonin gene related peptide. Additionally, triptan administration elicited a behavioural syndrome of enhanced sensitivity to surrogate triggers of migraine that was maintained for weeks following discontinuation of drug, a phenomenon termed 'triptan-induced latent sensitization'. Here, we demonstrate that triptan administration elicits a long-lasting increase in identified rat trigeminal dural afferents labelled for neuronal nitric oxide synthase in the trigeminal ganglion. Cutaneous allodynia observed during the period of triptan administration was reversed by NXN-323, a selective inhibitor of neuronal nitric oxide synthase. Additionally, neuronal nitric oxide synthase inhibition prevented environmental stress-induced hypersensitivity in the post-triptan administration period. Co-administration of NXN-323 with sumatriptan over several days prevented the expression of allodynia and enhanced sensitivity to stress observed following latent sensitization, but not the triptan-induced increased labelling of neuronal nitric oxide synthase in dural afferents. Triptan administration thus promotes increased expression of neuronal nitric oxide synthase in dural afferents, which is critical for enhanced sensitivity to environmental stress. These data provide a biological basis for increased frequency of headache following triptans and highlight the potential clinical utility of neuronal nitric oxide synthase inhibition in preventing or treating medication overuse headache.
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PMID:Triptan-induced enhancement of neuronal nitric oxide synthase in trigeminal ganglion dural afferents underlies increased responsiveness to potential migraine triggers. 2062 71


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