Menstrual migraine: treatment options.

More than half of women with migraine note an association of headache attacks and their menstrual cycles. Headaches associated with menses are often more severe and disabling than headaches that occur other times of the month. First-line therapies include acute agents used for migraine in general; however, for many women, these therapies provide incomplete relief. In these situations, treatment options include short-term perimenstrual prevention employing nonsteroidal anti-inflammatory medications, triptans, or hormone-containing preparations. Should these options not suffice, or if menstrual cycles are irregular, continuous prevention using hormonal therapies or standard anti-migraine prophylaxis should be considered.

Efficacy endpoints in migraine clinical trials: the importance of assessing freedom from pain.

Many efficacy endpoints have been used in clinical trials of acute migraine pharmacotherapy. Headache response or headache relief (i.e., moderate/severe pain reduced to mild/no pain) at a single, specified time-point, traditionally the primary endpoint, and headache recurrence (i.e., return of pain after initial postdose relief) are inadequate. Headache relief does not provide information about pain-free response and counts a partial response as a treatment success. Headache recurrence can reflect sustained efficacy but is confounded by initial response to treatment, because ineffective drugs have low recurrence rates. The International Headache Society (IHS) guidelines state that 2 hour pain-free response and sustained pain-free response (i.e., freedom from pain with no recurrence or use of rescue or study medication 2-24 hours postdose) provide the most clinically relevant information about the efficacy of migraine pharmacotherapy. The pain-free criterion counts partial responses as failures and thus is a more rigorous test of therapeutic benefit than headache relief, and the two endpoints together incorporate the main treatment attributes that determine patient satisfaction. As an example, consider needle-free subcutaneous sumatriptan and oral triptan tablets. An open-label study of needle-free subcutaneous sumatriptan by Cady and colleagues found that 2 hour pain-free response and sustained pain-free response were 64% and 42% respectively. For oral triptan tablets, the 2001 metaanalysis by Ferrari and colleagues reported 2 hour pain-free response rates ranging from 23% to 38% and sustained pain-free response rates ranging from 11% to 26%. The measures of pain-free response 2 hours postdose and sustained pain-free response can differentiate among treatments and be used to guide therapeutic choices.

Treatment satisfaction and efficacy of the rapid release formulation of sumatriptan 100 mg tablets utilising an early intervention paradigm in patients previously unsatisfied with sumatriptan.

AIMS: To evaluate treatment satisfaction, efficacy and functional ability of the rapid release formulation of sumatriptan 100 mg tablets (sumatriptan RT 100 mg) in an early intervention paradigm in patients who were dissatisfied with low-dose sumatriptan and not completely satisfied with their current migraine regimen. METHODS: Experienced migraineurs who reported a mild migraine pain phase, dissatisfaction with the previous sumatriptan treatment and some dissatisfaction with their current treatment regimen had no experience with sumatriptan at the 100 mg dose were enrolled in an open-label, single group study. Subjects were instructed to treat four migraine attacks within 30 min of the onset of mild pain. Treatment satisfaction was measured with the Patient Perception of Migraine Questionnaire Revised version (PPMQ-R) questionnaire. RESULTS: More than half of the subjects were either very satisfied or satisfied with the efficacy of early intervention sumatriptan RT 100 mg after each attack and at the follow-up study visit. The mean total PPMQ-R score was 75.2 out of 100. Between 63% and 73% of subjects were pain-free within 4 h of dosing. Between 79% and 90% of subjects reported an ability to function normally within 4 h of taking the study medication. CONCLUSION: Subjects who were previously unsatisfied with lower doses of sumatriptan and less than very satisfied with their current treatment regimen were more likely to be satisfied or very satisfied with sumatriptan RT 100 mg in an early intervention paradigm. Results were consistent across four migraine attacks and at a follow-up visit. The treatment satisfaction results corresponded with positive results on efficacy measures and a functional status measure.

Migraine MLT-down: an unusual presentation of migraine in patients with aspartame-triggered headaches.

Aspartame, an artificial sweetener added to many foods and beverages, may trigger headaches in susceptible individuals. We report two patients with aspartame-triggered attacks in whom the use of an aspartame-containing acute medication (Maxalt-MLT) worsened an ongoing attack of migraine.

Cluster and related headaches.

The disorders described in this article are relatively rare, but probably are more common than previously thought. Because these disorders cause significant pain and disability and treatment response differs from that of migraine, tension-type, and cluster headaches, recognition is essential. Table 1 lists the important clinical features of these syndromes and contrasts them with cluster headache, the disorder for which they are often confused.

Stabbing headache as the presenting manifestation of intracranial meningioma: a report of two patients.

Stabbing headache may occur as a primary headache disorder, may accompany other primary headaches, or, in rare instances, may be associated with secondary headache syndromes. We report two patients with intracranial meningioma in whom stabbing headache was the heralding symptom. Headache remitted promptly following surgical resection. These cases stress the importance of excluding underlying pathology in patients presenting with new-onset stabbing headache.

Testing and comparison of non-opioid analgesics in amphibians.

Because of the lack of information about effective analgesics in non-mammalian vertebrates, the potency of various non-opioid agents were tested in a model of analgesia by using Northern grass frogs (Rana pipiens). This alternative model has been used widely for investigating opioid analgesic action. Potential non-opioid analgesics tested included antipsychotic, benzodiazepine, barbiturate, antihistamine, non-steroidal anti-inflammatory (NSAID), and partial opioid agents. Northern grass frogs were acclimated to lab conditions in individual cages. Drugs were administered systemically through the dorsal lymph sac, and analgesic effects were estimated by using the acetic acid test (AAT). The AAT is done by placing logarithmic dilutions of acid dropwise on the dorsum of the animal's thigh until a wiping response is obtained. At various doses, chlorpromazine and haloperidol (antipsychotics), chlordiazepoxide (a benzodiazepine), buprenorphine (a partial opioid agonist), and diphenhydramine (a histamine antagonist) produced moderate to strong analgesic effects. Indomethacin and ketorolac (NSAIDs), butorphanol (a partial opioid agonist), and pentobarbital (a barbiturate) produced weaker but noticeable analgesic effects. Our results are the first to document the effectiveness of a wide array of pharmacologically active agents in a novel amphibian model for analgesia. These findings provide needed data regarding the use of alternative, non-opioid agents for the treatment of pain in amphibians and other poikilothermic species.

Effective management of ice pick pains, SUNCT, and episodic and chronic paroxysmal hemicrania.

Idiopathic stabbing headaches, the SUNCT syndrome, and the paroxysmal hemicranias are a group of primary headache disorders that are characterized by brief, short-lived attacks of head pain, which recur multiple times throughout the day. These syndromes are much less prevalent than other types of primary headaches such as migraine and tension-type headaches but are significantly more disabling. Recognition of these uncommon disorders is important because their management differs from standard headache therapies.

Selective opioid agonist and antagonist competition for [3H]-naloxone binding in amphibian spinal cord.

Opioids elicit antinociception in mammals through three distinct types of receptors designated as mu, kappa and delta. However, it is not clear what type of opioid receptor mediates antinociception in non-mammalian vertebrates. Radioligand binding techniques were employed to characterize the site(s) of opioid action in the amphibian, Rana pipiens. Naloxone is a general opioid antagonist that has not been characterized in Rana pipiens. Using the non-selective opioid antagonist, [3H]-naloxone, opioid binding sites were characterized in amphibian spinal cord. Competitive binding assays were done using selective opioid agonists and highly-selective opioid antagonists. Naloxone bound to a single-site with an affinity of 11.3 nM and 18.7 nM for kinetic and saturation studies, respectively. A B(max) value of 2725 fmol/mg protein in spinal cord was observed. The competition constants (K(i)) of unlabeled mu, kappa and delta ranged from 2.58 nM to 84 microM. The highly-selective opioid antagonists yielded similar K(i) values ranging from 5.37 to 31.1 nM. These studies are the first to examine opioid binding in amphibian spinal cord. In conjunction with previous behavioral data, these results suggest that non-mammalian vertebrates express a unique opioid receptor which mediates the action of selective mu, kappa and delta opioid agonists.

Selective opioid receptor agonist and antagonist displacement of [3H]naloxone binding in amphibian brain.

Opioid receptor ligands have been shown to elicit antinociception in mammals through three distinct types of receptors designated as mu, delta and kappa. These opioid receptors have been characterized and cloned in several mammalian species. Radioligand binding techniques were employed to characterize the sites of opioid action in the amphibian, Rana pipiens. Naloxone is a general opioid receptor antagonist which has not been characterized in R. pipiens. Kinetic analyses of [3H]naloxone in the amphibian yielded a K(D) of 6.84 nM while the experimentally derived K(D) value from saturation experiments was found to be 7.11 nM. Density data were also determined from saturation analyses which yielded a B(max) of 2170 fmol/mg. Additionally, K(i) values were calculated in competition studies for various unlabelled mu-, delta- and kappa-opioid receptor ligands to isolate their site of action. Highly selective antagonists for mu-, delta- and kappa-opioid receptors yielded nearly identical K(i) values against [3H]naloxone.

Migraine: clinical features and diagnosis.

Migraine is a syndrome characterized by recurrent headaches with or without aura. Triggers include foods, hormonal changes, and stressors. Migraine must be differentiated from other unilateral headache disorders and from headaches due to other neurologic and systemic diseases.

Characterization of [3H]-diprenorphine binding in Rana pipiens: observations of filter binding enhanced by naltrexone.

Initial studies were undertaken to examine the properties of [3H]-diprenorphine binding to Rana pipiens whole brain tissue using naltrexone for the definition of nonspecific binding. Saturation analysis demonstrated the binding of [3H]-diprenorphine to be saturable with a K(D) value of 0.65 nM and a Bmax value of 287.7 fmol/mg protein. Unlabeled diprenorphine dose-dependently displaced [3H]-diprenorphine from a single noninteractive site in competition studies which yielded a Ki of 0.22 nM. However, control studies in the absence of tissue revealed significant binding of [3H]-diprenorphine to the filter alone. Interestingly, [3H]-diprenorphine in the presence of unlabeled naltrexone as well as with unlabeled naloxone showed significantly greater binding to the filter than did [3H]-diprenorphine alone. Given this observation of increased nonspecific binding, an artificially low Bmax value would be expected. It is our hypothesis that the unlabeled nonspecific drug forms a complex with [3H]-diprenorphine preventing it from being effectively washed through the filter or the unlabeled drug itself is blocking the flow of [3H]-diprenorphine through the filter. The latter is unlikely however as other binding studies done in our lab using the radioligand [3H]-naloxone with unlabeled naltrexone do not show significant binding to the filter.

Spinal administration of selective opioid antagonists in amphibians: evidence for an opioid unireceptor.

In mammals, opioids act by interactions with three distinct types of receptors: mu, delta, or kappa opioid receptors. Using a novel assay of antinociception in the Northern grass frog, Rana pipiens, previous work demonstrated that selective mu, delta, or kappa opioids produced a potent antinociception when administered by the spinal route. The relative potency of this effect was highly correlated to that found in mammals. Present studies employing selective opioid antagonists, beta-FNA, NTI, or nor-BNI demonstrated that, in general, these antagonists were not selective in the amphibian model. These data have implications for the functional evolution of opioid receptors in vertebrates and suggest that the tested mu, delta, and kappa opioids mediate antinociception via a single type of opioid receptor in amphibians, termed the unireceptor.

Chronic daily bilateral headache responsive to indomethacin.

Indomethacin is known to be specifically effective for chronic paroxysmal hemicrania, episodic paroxysmal hemicrania, and hemicrania continua. Different forms of idiopathic stabbing headaches have also been responsive to indomethacin, but less consistently than the others. Two cases of indomethacin-responsive headache are reported. One patient presented with what appeared to be new-onset, chronic, daily, bilateral headache aggravated by coughing. Both the chronic daily headache and the exacerbations induced by coughing were suppressed with indomethacin therapy. The second patient experienced hemicrania continua responsive to indomethacin, and the response persisted even when the headache evolved into bilateral continuous pain. There may be other idiopathic primary headache disorders that are peculiarly responsive to indomethacin. When any primary headache disorder does not respond to standard therapy, a brief therapeutic trial of indomethacin is warranted.

Posttraumatic hemicrania continua.

Hemicrania continua is a rare, benign headache disorder characterized by a low-level baseline hemicranial headache with superimposed exacerbations of more severe pain. Exacerbations last from minutes to days and may be associated with ipsilateral autonomic features such as ptosis, miosis, conjunctival injection, lacrimation, or rhinorrhea; when present, these features tend to be less pronounced than those seen with cluster headache. Response to treatment with indomethacin, in doses ranging from 25 to 300 mg per day, has been deemed a sine qua non of diagnosis. To date, in the majority of instances, hemicrania continua appears to have arisen de novo, without any identifiable trigger. We report four patients in whom the onset of hemicrania continua was temporally linked to head trauma.

A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine.

Headaches associated with menstruation are often resistant to abortive and preventative medications. We performed an open-label study in 20 female migraineurs, employing oral sumatriptan perimenstrually as short-term prophylaxis of menstrual migraine. In 126 sumatriptan-treated cycles, headache was absent in 52.4% and reduced in severity by 50% or greater in 42%. Breakthrough headaches were rare and significantly reduced in severity compared with baseline headaches.

Emergency department evaluation of headache.

Headache is an extremely common complaint in the Emergency Department, accounting for up to 16% of all visits. Although there are more than 300 medical conditions which can produce headache, the vast majority of headache disorders are benign. This article outlines an orderly approach for evaluating patients who present with headaches; in addition, the authors discuss the emergency treatment of the more common types of headache.

Cardiac cephalgia: a treatable form of exertional headache.

We report two patients with exertional headaches beginning with vigorous exercise and relieved by rest. Neurologic evaluation and neuroimaging were normal in both. During exercise stress testing, the onset of the patients' typical headaches correlated with ECG changes indicative of myocardial ischemia. In both patients coronary angiography revealed three-vessel disease, and myocardial revascularization procedures were followed by complete resolution of headaches. Based on these patients, and a review of prior similar reports, we conclude that myocardial ischemia is a rare and treatable cause of exertional headache. Accurate diagnosis is critical to controlling headaches and preventing myocardial infarction.

Sumatriptan relieves migrainelike headaches associated with carbon monoxide exposure.

We report a 58-year-old woman with long-standing migraine who developed a pattern of weekend headaches which occurred only while staying at her Connecticut vacation home. The headaches promptly responded to sumatriptan. Investigation revealed a high carbon monoxide level in her home due to a defective furnace. Replacing the furnace eliminated the headaches. This case highlights the importance of searching for secondary causes of headache even in patients responsive to sumatriptan. It also suggests that carbon monoxide may trigger headaches mediated by trigeminovascular inflammation.

The site of common side effects of sumatriptan.

Atypical sensations following the use of subcutaneous sumatriptan are common, but of uncertain origin. They are almost always benign, but can be mistaken for a serious adverse event by the patient. Two patients are presented with tingling or burning sensations limited to areas of heat exposure or sunburn. In these individuals, side effects are most likely generated superficially in the skin.