http://link.springer.com/article/10.1007/s10072-013-1415-8
This is a very interesting study that investigates the possibility that in people with migraine there also occurs some trouble with dopamine regulation in the brain. See below:
"Our review suggests that when the attack begins, a low dopamine plasma concentration stimulates hypersensitive central presynaptic dopamine receptors thus causing prodromal symptoms such as yawning and somnolence. Increasing dopamine levels, though still insufficient to stop trigeminovascular activation, stimulate postsynaptic dopamine receptors thus inducing nausea, vomiting and hypotension. Finally, dopamine levels slowly return to baseline, giving rise to somnolence and fatigue, but, in some cases, continue to rise triggering postdromal symptoms such as euphoria and polyuria."
"Strong evidence indicates that serotonin plays a major role in migraine probably acting on central pain control pathways and on cranial blood vessels. In 1977, Sicuteri [2] proposed as the second putative protagonist in migraine dopamine (DA); since then, intensive research has investigated DA and migraine. In this review, we outline research advances underlining how DA intervenes in migraine symptoms and mechanisms."
"Almost 30 % of migraineurs report experiencing prodromal symptoms hours before the headache begins. They typically feel tired, somnolent and drowsy, yawn excessively, and crave for foods. During the pain phase, nausea, vomiting and sometimes hypotension may induce severe disability. In the postdromal phase, which often needs eliciting, patients are usually tired and weak but sometime feel euphoric [1]. Most, if not all, symptoms preceding, accompanying and following the headache in migraineurs resemble those induced by pharmacologically induced central or peripheral DA receptor (DR) stimulation."
"Pharmacological challenges with DA agonists indicate that dopaminergic hypersensitivity is a specific trait in migraine patients. When given to migraineurs at small (nanomolar) doses, the DRD1-like and DRD2-like agonist apomorphine acts on presynaptic DRs thus reducing DA transmission, whereas at higher doses it acts on postsynaptic DRs thereby stimulating DA transmission. As a pharmacological tool, apomorphine has done much to unmask dopaminergic hypersensitivity in migraine. At the dose of 5 μg/kg sc or 0.25 mg sl it induces a significantly greater number of yawns in migraine sufferers than in controls [4, 5], whereas at the dose of 10 μg/kg sc (by stimulating presynaptic DRs) it causes at the most yawning and drowsiness in controls but (by stimulating postsynaptic DRs) it also causes nausea and vomiting in migraineurs [6]. The DA agonist piribedil at the dose of 0.1 mg/kg iv increases cerebral blood flow and induces nausea, vomiting and hypotension only in migraineurs [7]. In migraineurs but not in healthy controls, bromocriptine (2.5 mg po) provokes an intense hypotensive reaction unrelated to DA beta-hydroxylase plasma levels, suggesting defective central DA control on blood pressure and central DR hypersensitivity [8]."
"All the aforementioned studies demonstrate that presynaptic and postsynaptic DRs in migraine sufferers have a low activation threshold, in keeping with a chronic dopaminergic hypofunction."
"Biochemical change could reflect reduced activity of the enzyme DA beta-hydroxylase which catalyzes DA conversion into norepinephrine. In their study, D’Andrea et al. also suggest that during the migraine attack, impaired energy metabolism shifts tyrosine metabolism from hydroxylation, which physiologically gives rise to a metabolic cascade leading to catecholamine synthesis, toward decarboxylation, resulting in increased synthesis of trace amines (tyrosine, octopamine, synephrine). The imbalance between neurotransmitters (DA, norepinephrine) and neuromodulators (trace amines) activates the trigeminovascular system [13]."
"The substantia nigra (SN), a brain area that actively controls the cerebral cortical microcirculation and neuronal activity, contains a high density of 5HT1B receptors, targeted by triptans [25]. Objective evidence confirming SN involvement in migraine comes from a functional magnetic resonance imaging study showing blood oxygen level-dependent SN activation during visually triggered migraine [26]. Parkinson’s disease (PD), the paradigm for DA system impairment, seems to shorten the clinical course of migraine. In a study on 237 PD patients aimed to assess the prevalence of lifetime and current migraine, approximately two-thirds of patients reported that migraine improved or remitted after PD onset [27]. SN degeneration, the PD hallmark, could be responsible for the migraine decline in parkinsonian patients, reinforcing the view that migraine needs an efficient DA system. Again underlining dopaminergic system involvement in migraine, patients with PD and current or prior migraine respond better to dopaminergic medications and experience less severe disabilities than patients without migraine, further supporting dopaminergic hypersensitivity in migraine [28]."
"More help in understanding trigeminal DA mechanisms in migraine comes from a study conducted in recent years showing that DRD2 and 5-HT1B/1D receptors are colocalized in the trigeminocervical complex, suggesting that DA and serotonin act simultaneously and synergistically at that level to reduce neuronal firing and to reverse trigeminal sensitization [30]."
Lisuride, an 8-α-amino-ergoline derivative with a high affinity for DRD1 and DRD2, at the dose 0.05–0.075 mg significantly reduces attack frequency and severity [32]. α-Dihydroergocryptine, a semisynthetic ergot derivative, is a DR agonist which at the dose of 10 mg bid is as effective as flunarizine in migraine prevention [33]. Evidence that DR stimulation is meaningful for migraine prevention is apparently weakened by the potential neuroleptic-like profile of flunarizine, an established antimigraine prophylactic agent characterized by the risk of inducing parkinsonism in the elderly. Its therapeutic action in migraine could, however, be independent from antidopaminergic mechanisms..."
"In acute migraine treatment, DR antagonists have recognized efficacy. Domperidone, a peripheral DRD1–DRD2 antagonist, taken at doses ranging from 20 to 40 mg during prodromes, may stop progression to the headache phase [36]. Metoclopramide (10–20 mg), taken alone or combined with other agents, is an effective acute migraine treatment not only for nausea and vomiting but also for headache. Other neuroleptics, i.e., prochlorperazine (5–10 mg), chlorpromazine (25–100 mg), droperidol (1.25–2.5 mg) and haloperidol (2–5 mg), regardless of the delivery route, provide effective acute migraine treatment and in some comparative studies outperform NSAIDs, valproate, opioids and sumatriptan [37]."
This is a very interesting study that investigates the possibility that in people with migraine there also occurs some trouble with dopamine regulation in the brain. See below:
"Our review suggests that when the attack begins, a low dopamine plasma concentration stimulates hypersensitive central presynaptic dopamine receptors thus causing prodromal symptoms such as yawning and somnolence. Increasing dopamine levels, though still insufficient to stop trigeminovascular activation, stimulate postsynaptic dopamine receptors thus inducing nausea, vomiting and hypotension. Finally, dopamine levels slowly return to baseline, giving rise to somnolence and fatigue, but, in some cases, continue to rise triggering postdromal symptoms such as euphoria and polyuria."
"Strong evidence indicates that serotonin plays a major role in migraine probably acting on central pain control pathways and on cranial blood vessels. In 1977, Sicuteri [2] proposed as the second putative protagonist in migraine dopamine (DA); since then, intensive research has investigated DA and migraine. In this review, we outline research advances underlining how DA intervenes in migraine symptoms and mechanisms."
"Almost 30 % of migraineurs report experiencing prodromal symptoms hours before the headache begins. They typically feel tired, somnolent and drowsy, yawn excessively, and crave for foods. During the pain phase, nausea, vomiting and sometimes hypotension may induce severe disability. In the postdromal phase, which often needs eliciting, patients are usually tired and weak but sometime feel euphoric [1]. Most, if not all, symptoms preceding, accompanying and following the headache in migraineurs resemble those induced by pharmacologically induced central or peripheral DA receptor (DR) stimulation."
"Pharmacological challenges with DA agonists indicate that dopaminergic hypersensitivity is a specific trait in migraine patients. When given to migraineurs at small (nanomolar) doses, the DRD1-like and DRD2-like agonist apomorphine acts on presynaptic DRs thus reducing DA transmission, whereas at higher doses it acts on postsynaptic DRs thereby stimulating DA transmission. As a pharmacological tool, apomorphine has done much to unmask dopaminergic hypersensitivity in migraine. At the dose of 5 μg/kg sc or 0.25 mg sl it induces a significantly greater number of yawns in migraine sufferers than in controls [4, 5], whereas at the dose of 10 μg/kg sc (by stimulating presynaptic DRs) it causes at the most yawning and drowsiness in controls but (by stimulating postsynaptic DRs) it also causes nausea and vomiting in migraineurs [6]. The DA agonist piribedil at the dose of 0.1 mg/kg iv increases cerebral blood flow and induces nausea, vomiting and hypotension only in migraineurs [7]. In migraineurs but not in healthy controls, bromocriptine (2.5 mg po) provokes an intense hypotensive reaction unrelated to DA beta-hydroxylase plasma levels, suggesting defective central DA control on blood pressure and central DR hypersensitivity [8]."
"All the aforementioned studies demonstrate that presynaptic and postsynaptic DRs in migraine sufferers have a low activation threshold, in keeping with a chronic dopaminergic hypofunction."
"Biochemical change could reflect reduced activity of the enzyme DA beta-hydroxylase which catalyzes DA conversion into norepinephrine. In their study, D’Andrea et al. also suggest that during the migraine attack, impaired energy metabolism shifts tyrosine metabolism from hydroxylation, which physiologically gives rise to a metabolic cascade leading to catecholamine synthesis, toward decarboxylation, resulting in increased synthesis of trace amines (tyrosine, octopamine, synephrine). The imbalance between neurotransmitters (DA, norepinephrine) and neuromodulators (trace amines) activates the trigeminovascular system [13]."
"The substantia nigra (SN), a brain area that actively controls the cerebral cortical microcirculation and neuronal activity, contains a high density of 5HT1B receptors, targeted by triptans [25]. Objective evidence confirming SN involvement in migraine comes from a functional magnetic resonance imaging study showing blood oxygen level-dependent SN activation during visually triggered migraine [26]. Parkinson’s disease (PD), the paradigm for DA system impairment, seems to shorten the clinical course of migraine. In a study on 237 PD patients aimed to assess the prevalence of lifetime and current migraine, approximately two-thirds of patients reported that migraine improved or remitted after PD onset [27]. SN degeneration, the PD hallmark, could be responsible for the migraine decline in parkinsonian patients, reinforcing the view that migraine needs an efficient DA system. Again underlining dopaminergic system involvement in migraine, patients with PD and current or prior migraine respond better to dopaminergic medications and experience less severe disabilities than patients without migraine, further supporting dopaminergic hypersensitivity in migraine [28]."
"More help in understanding trigeminal DA mechanisms in migraine comes from a study conducted in recent years showing that DRD2 and 5-HT1B/1D receptors are colocalized in the trigeminocervical complex, suggesting that DA and serotonin act simultaneously and synergistically at that level to reduce neuronal firing and to reverse trigeminal sensitization [30]."
Lisuride, an 8-α-amino-ergoline derivative with a high affinity for DRD1 and DRD2, at the dose 0.05–0.075 mg significantly reduces attack frequency and severity [32]. α-Dihydroergocryptine, a semisynthetic ergot derivative, is a DR agonist which at the dose of 10 mg bid is as effective as flunarizine in migraine prevention [33]. Evidence that DR stimulation is meaningful for migraine prevention is apparently weakened by the potential neuroleptic-like profile of flunarizine, an established antimigraine prophylactic agent characterized by the risk of inducing parkinsonism in the elderly. Its therapeutic action in migraine could, however, be independent from antidopaminergic mechanisms..."
"In acute migraine treatment, DR antagonists have recognized efficacy. Domperidone, a peripheral DRD1–DRD2 antagonist, taken at doses ranging from 20 to 40 mg during prodromes, may stop progression to the headache phase [36]. Metoclopramide (10–20 mg), taken alone or combined with other agents, is an effective acute migraine treatment not only for nausea and vomiting but also for headache. Other neuroleptics, i.e., prochlorperazine (5–10 mg), chlorpromazine (25–100 mg), droperidol (1.25–2.5 mg) and haloperidol (2–5 mg), regardless of the delivery route, provide effective acute migraine treatment and in some comparative studies outperform NSAIDs, valproate, opioids and sumatriptan [37]."
