Onset of cluster headache triggered by emotional effect: a case report.
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Cluster Headache↗
Biomedical subjects
P J Goadsby
Publications and source records attributed to P J Goadsby.
Orexin 1 receptor activation attenuates neurogenic dural vasodilation in an animal model of trigeminovascular nociception.
The pathophysiology underlying the pulsating quality of the pain of a migraine attack is not fully understood, although trigeminal vascular afferents containing the sensory neuropeptide calcitonin gene-related peptide (CGRP) must have a role. Antimigraine drugs, such as triptans, serotonin 5-hydroxytryptamine(1B/1D) receptor agonists, reproducibly block neurogenic vasodilation associated with CGRP release. We examined the effects of the hypothalamic neuropeptides orexin A and orexin B on neurogenic dural vasodilation, dissecting out the receptor pharmacology with the novel orexin 1 (OX1) receptor antagonist N-(2-methyl-6-benzoxazolyl)-N''-1,5-naphthyridin-4-yl urea (SB-334867). Electrical stimulation of dural afferents (50-300 microA) resulted in reproducible dural vasodilation of 136 +/- 9%. Orexin A 30 microg kg(-1), but not 3 and 10 microg kg(-1), inhibited the dilation brought about by electrical stimulation over 60 min and maximally after 15 min by 60% (t7= 7.138; P < 0.001; n = 8). This response was reversed by pretreatment with the OX1 receptor antagonist SB-334867. Addition of CGRP(8-37) at the point of maximal effect of orexin A produced a further significant decrease in neurogenic dural vasodilation compared with orexin A only. CGRP administration (1 microg kg(-1)) produced a reproducible dural blood vessel dilation of 145 +/- 7% that was not inhibited by intravenous administration of orexin A (30 microg kg(-1)). Orexin B had no significant effect even at the highest dose. The current study demonstrates that orexin A is able to inhibit neurogenic dural vasodilation via activation of the OX1 receptor, resulting in inhibition of prejunctional release of CGRP from trigeminal neurons.
Animals↗
Properties of neurons in the trigeminal nucleus caudalis responding to noxious dural and facial stimulation.
Extracellular single unit recordings were made in the rat trigeminal nucleus caudalis (Vc) from cells with Adelta and C-fibre latency responding to electrical stimulation of the thinned cranium overlying the middle meningeal artery (MMA). The neurons had an ipsilateral facial receptive field (FRF) that mainly extended over areas innervated by the first and second division of the trigeminal nerve but in some cases also included areas innervated by the third division of the trigeminal nerve. No wind-up of either long latency C-fibre or short latency Adelta responses was seen during trains of electrical stimulation. Sensitisation of mechanical stimulation of the FRF could also not be observed at any time during dural stimulation. In contrast, extracellular single unit recordings in the Vc activated by electrical stimulation of the facial skin resulted in a significant wind-up response of long latency response in six of ten cells studied. The facial-elicited wind-up response was significantly enhanced, 18 min after the electrical stimulation protocol was started, indicating that the process of wind-up had generated central excitability. The findings in this study demonstrate a clear difference between the effects of electrical stimulation of cutaneous and non-cutaneous inputs. In the trigeminal system, this has implications for the study of pathways such as those involved in headache, where it is believed that an enhanced dural input to the Vc may generate central sensitisation and partly explain the hyperalgesia and allodynia reported by patients.
Afferent Pathways↗
The clinical characteristics of headache in patients with pituitary tumours.
The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache were investigated. The patients presented with chronic (46%) and episodic (30%) migraine, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT; 5%), cluster headache (4%), hemicrania continua (1%) and primary stabbing headache (27%). It was not possible to classify the headache according to International Headache Society diagnostic criteria in six cases (7%). Cavernous sinus invasion was present in the minority of presentations (21%), but was present in two of three patients with cluster headache. SUNCT-like headache was only seen in patients with acromegaly and prolactinoma. Hypophysectomy improved headache in 49% and exacerbated headache in 15% of cases. Somatostatin analogues improved acromegaly-associated headache in 64% of cases, although rebound headache was described in three patients. Dopamine agonists improved headache in 25% and exacerbated headache in 21% of cases. In certain cases, severe exacerbations in headache were observed with dopamine agonists. Headache appears to be a significant problem in pituitary disease and is associated with a range of headache phenotypes. The presenting phenotype is likely to be governed by a combination of factors, including tumour activity, relationship to the cavernous sinus and patient predisposition to headache. A proposed modification of the current classification of pituitary-associated headache is given.
Adenoma↗
The role of dopamine in a model of trigeminovascular nociception.
Migraine is a common, disabling problem with three phases: premonitory, main headache attack, and postdrome. The headache phase is thought to involve activation of trigeminal neurons, whereas the premonitory and postdrome phases may involve dopaminergic mechanisms. In animal studies, dopamine has been found to cause vasodilation of cranial arteries at very low doses. Using intravital microscopy, we examined the effect of dopamine receptor agonists on dural blood vessel caliber and the effect of dopamine and specific dopamine receptor antagonists on trigeminovascular neurogenic dural vasodilation. Dopamine hydrochloride caused a significant vasoconstriction (P < 0.05) and increase in arterial blood pressure (P < 0.05) that was reversed by a alpha2-adrenoceptor antagonist, yohimbine, rather than specific dopamine receptor antagonists. The D1 receptor agonist caused a vasoconstriction (P < 0.05) and a blood pressure increase (P < 0.05), which was reversed by yohimbine and therefore alpha2-adrenoceptor-mediated. None of the specific dopamine receptor antagonists were able to attenuate neurogenic dural vasodilation. Dopamine hydrochloride infusion (P < 0.05) and a D1 receptor agonist were able to attenuate the vasodilation (P < 0.05), with maximal dilation returning after cessation of the dopamine agonist infusion. This response may be due to the vasoconstrictor effects of the alpha2-adrenoceptor and an action at the D1 receptor. In the intravital model of trigeminal activation, it seems that dopamine receptors do not play a major role and may not present an acute treatment option. Our data do not exclude a role for dopamine receptor modulators in short- or long-term prevention.
Adrenergic alpha-2 Receptor Antagonists↗
The use of multiattribute decision models in evaluating triptan treatment options in migraine.
BACKGROUND: The physician treating patients with migraine is now able to choose from among seven triptans-almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser degrees, on a range of clinical attributes important for treatment selection. OBJECTIVE: To outline the basic principles of Multiattribute Decision Making (MADM) and describe how one such method-TOPSIS (Technique for Order Preference by Similarity to the Ideal Solution)-can be applied to evaluate the currently available triptans. METHODS: In an example application, summary data from a recent meta-analysis of 53 published and unpublished placebo-controlled trials of the oral triptans were combined in TOPSIS models with computer-generated attribute importance weights representing the entire range of possible values, That is, the relative performance of the triptans was explored across all logically possible combinations of relative importance of the treatment attributes available from the meta-analysis, and uncertainty was assessed based on the confidence intervals from the meta-analysis. RESULTS: When compared across the entire range of values for relative attribute importance, almotriptan, eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and were more likely to appear in the top three closest to the hypothetical ideal, than were naratriptan, sumatriptan, and zolmitriptan. CONCLUSION: Using the TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear in the top three closest to the hypothetical ideal triptan.
Clinical Trials as Topic↗
Paroxysmal raised intracranial pressure associated with spinal meningeal cysts.
Raised intracranial pressure in association with spinal meningeal cysts has rarely been reported. We describe four patients in whom evidence of paroxysmal raised intracranial pressure was found in association with spinal meningeal cysts. Cerebrospinal fluid diversion procedures have previously been shown to relieve local symptoms due to spinal cysts. In our patients symptoms of paroxysmal headache were alleviated by this method, suggesting a causal relationship with the raised pressure. This association may be an under diagnosed cause of paroxysmal headaches. We review the medical literature on the classification of spinal meningeal cysts, evaluate the theories of their origin and offer suggestions on the pathogenesis of the abnormal CSF dynamics that may allow an interplay between raised intracranial pressure and spinal meningeal cysts to produce paroxysmal symptoms.
Adolescent↗
A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate.
Migraine is a common disabling condition likely to be associated with dysfunction of brain pathways involved in pain and other sensory modalities. A cardinal, indeed signature, feature of the disorder that led to its name is that the pain may be lateralized. H(2)15O-labelled PET was used to study 24 migraineurs and eight healthy controls. The migraineurs were divided into three groups according to the site of their headache: right, left or bilateral. In each group, a migraine was induced using a glyceryl trinitrate (GTN) infusion. The subjects were scanned at predefined points: pre-infusion, during GTN, during migraine and post-migraine. SPM99 software was used to analyse the data. Significant brainstem activation was seen in the dorsal lateral pons (P < 0.05 after small volume correction) during the migraine state versus the pain-free state when comparing migraineurs with controls. When each group was analysed separately, to investigate laterality, it was found that the dorsal pontine activation was ipsilateral in the right-sided and left-sided groups and bilateral in the bilateral headache group with a left-sided preponderance. Consistent with previous work, the activation persisted after pain was controlled by sumatriptan. These results suggest that lateralization of pain in migraine is due to lateralized brain dysfunction.
Adult↗
Calcium channels modulate nociceptive transmission in the trigeminal nucleus of the cat.
Clinical observations and genetic studies have suggested a role for high-threshold voltage-dependent calcium channels (VDCCs) in the pathogenesis of migraine. This study investigated the role of P/Q-, L- and N-type VDCCs in post-synaptic action potential generation in trigeminovascular nociceptive afferents in the trigeminocervical complex (TCC) of the cat in vivo. Trigeminovascular nociceptive afferents were identified in the TCC by electrical stimulation of the superior sagittal sinus. Forty-six cell bodies were identified by their response to microiontophoresis of l-glutamate and their bipolar action potential shape. Blockade of VDCCs was accomplished by microiontophoresis of omega-agatoxin IVa/TK (P/Q-), omega-conotoxin GVIa (N-) and calciseptine (L-type). Non-selective antagonism was studied using cadmium ions. Non-selective blockade of high threshold VDCC with cadmium resulted in a reduction in l-glutamate-evoked neuronal activity (P=0.01). Blockade of P/Q: TK- (P<0.001), IVA- (P=0.007), L- (P<0.001) and N-type (P<0.001) VDCCs resulted in significant reductions in post-synaptic action potential generation in response to l-glutamate. High threshold VDCCs, including P/Q-, L- and N-type VDCCs, can therefore modulate nociceptive transmission in the trigeminocervical complex in vivo. We discuss the evidence to suggest a role for VDCCs in the pathophysiology of primary headache disorders, and how abnormalities of function may contribute to their pathogenesis.
Action Potentials↗
Inhibition of nociceptive dural input in the trigeminal nucleus caudalis by somatostatin receptor blockade in the posterior hypothalamus.
Somatostatin is a neuromodulator in the central nervous system and is involved in the regulation of metabolic and neuroendocrine functions. Recent experimental and clinical findings point to a role for somatostatin in the central processing of nociception. We studied the effects of somatostatin receptor modulation in the posterior hypothalamic area (PH) of the rat on dural nociceptive input. Somatostatin (10 microg/microl) and the somatostatin antagonist cyclo-somatostatin (50 microg/microl) were microinjected into the PH and the effects on responses of neurons in the trigeminal subnucleus caudalis studied. Injection of somatostatin (n=11) did not affect A- and C-fibre responses to dural electrical stimulation, nor was spontaneous activity altered (P>0.05). Injection of cyclo-somatostatin (n=10) into the PH reduced A-(-35.5+/-5.8%) and C-fibre (-43.1+/-7.5%) responses to dural stimulation and resulted in decreased spontaneous activity (-38.1+/-7.3%, P<0.05). Responses to facial thermal stimulation were decreased by 51.2+/-5.8% (n=5). Control injections had no significant effect (n=9). Blockade of somatostatin receptors in the PH has an anti-nociceptive effect on dural and facial input, probably mediated via GABAergic mechanisms. As somatostatin is also involved in hypothalamic regulation of metabolic, neuroendocrine and autonomic functions, somatostatin receptor mechanisms in the PH may play a role in the pathophysiology of primary headache disorders, such as migraine or cluster headache.
Action Potentials↗
Trigeminal autonomic cephalalgias. Pathophysiology and classification.
Trigeminal Autonomic Cephalalgias (TACs) is a grouping of headache syndromes that includes cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). They are recognized clinically by their episodic, stereotypic attack profile and very often prominent cranial autonomic symptoms, such as lacrimation, conjunctival injection or rhinorrhea. They involve afferent activation of the trigeminal innervation of intracranial pain-producing structures, or the perception of that activation, and reflex activation of the facial, seventh cranial, nerve outflow pathway. This excess reflex trigeminal-autonomic activation seems to be permitted by dysfunction in the brain, specifically in the posterior hypothalamic gray matter. Understanding the anatomy and physiology of these disorders has greatly facilitated their management and the development of exciting new strategies such as neuromodulatory approaches to the management of the more intractable cases.
Cluster Headache↗
Octreotide is not effective in the acute treatment of migraine.
The aim of this study was to determine whether subcutaneous octreotide is effective for the treatment of acute migraine. Patients with migraine with and without aura as classified by the International Headache Society were recruited to a double-blind placebo-controlled crossover study. Patients were instructed to treat two attacks of at least moderate pain severity, with at least a 7 day interval, using subcutaneous 100 microg octreotide or matching placebo. The primary endpoint was the headache response defined as: severe or moderate pain becomes mild or nil, at 2 h. The primary endpoint was analysed using a Multilevel Analysis approach. Secondary end-points included associated symptoms and a four-point functional disability score. The study was powered to detect a 30% difference at an alpha of 0.05 and a beta of 0.8. A total of 51 patients were recruited, of whom 42 provided efficacy data on an attack treated with octreotide and 41 with placebo. Modelling the headache response as a binomial determined by treatment, using the patient as the level 2 variable, and considering a possible period effect, and sex and migraine type as other variables of interest, subcutaneous octreotide was not significantly superior to placebo. The two hour headache response rates were 20% for placebo and 14% for octreotide, whilst the two hour pain free rates were 7% and 2%, respectively. Subcutaneous octreotide 100 microg is not effective in the acute treatment of migraine when compared to placebo.
Acute Disease↗
Diffusion- and perfusion-weighted MR imaging in persistent migrainous visual disturbances.
Pathological changes on diffusion-weighted MR scans had been described in hemiplegic migraine and perfusion changes had been demonstrated in typical migraine aura with radio-isotope studies and, more recently, MR perfusion imaging. However, there is relatively little knowledge of the pathophysiology of long-lasting migraine aura and its possibly variant phenotype, visual snow. Our aim was to investigate with advanced MR techniques whether patients with long-lasting visual disturbance showed regional alterations in cerebral water diffusion and perfusion. We have studied four patients using MR perfusion and MR diffusion imaging. Two patients had typical visual aura and two had a primary persistent visual disturbance (visual snow phenomenon). All patients had normal conventional structural MR imaging. MR diffusion-weighted images were acquired with a b-value of up to 1000 s/mm2. From the diffusion weighted images we generated maps of apparent diffusion coefficient (ADC), which were inspected visually and used for ADC measurements of predefined regions of interest, which included the visual, frontal, insular and temporal cortices. MR perfusion imaging was performed using a bolus tracking technique with dynamic susceptibility-weighted images. Colour coded maps of relative cerebral blood volume, mean transit time and bolus arrival time were generated, as well as time-signal intensity curves over the anterior, middle and posterior cerebral artery territories. The maps of the ADC and above perfusion parameters appeared symmetrical in all patients with no evidence of decreased water diffusion or cerebral perfusion in the occipital regions, or elsewhere. There was no statistically significant difference between the ADC measurements of the primary visual cortices and other cortical regions. Our findings suggest that regional changes in cerebral water diffusion and perfusion do not play an important part in the pathophysiology of persistent migraine aura or primary persistent visual disturbance.
Adult↗
Familial SUNCT.
Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare type of primary headache. In this report we describe the occurrence of SUNCT in a family. Unfortunately, one of the siblings was already dead. However, clear and detailed information from close relatives and her general practitioner confirmed the diagnosis of SUNCT. It is likely that genetic factors contribute to all types of trigeminal autonomic cephalalgias.
Aged↗
The International Classification of Headache Disorders, 2nd Edition (ICHD-II)--revision of criteria for 8.2 Medication-overuse headache.
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Analgesics↗
Bilateral paroxysmal hemicrania or bilateral paroxysmal cephalalgia, another novel indomethacin-responsive primary headache syndrome?
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Adolescent↗
No relationship between vasoactive intestinal polypeptide expression and headache in pituitary tumours.
BACKGROUND: Clinical studies have noted the common presentation of pituitary tumours with significant headache. This has been considered to be one, or a combination of, increased cranial pressure, tumour size with dural stretch, or cavernous sinus invasion. Newer hypotheses suggest an association between the presence of pituitary tumour-associated headaches and the expression and release of nociceptive substances. Vasoactive intestinal polypeptide (VIP), a marker of the cranial parasympathetic system, is increased during acute attacks of some primary headaches, and with its expression in the pituitary may link some pituitary tumours to their headache presentations. METHODS: Using immunohistochemical techniques, VIP expression in pituitary tumour specimens was examined to determine if there was a relationship between the presence or absence of pituitary-associated headache and the expression of VIP immunoreactivity (VIP-IR). A qualitative analysis of the VIP-IR in pituitary cells was performed by observers blinded to the headache status of each patient. The presence of VIP-IR and headache were treated as binary variables and associations tested with chi-square tests. RESULTS: Forty-five per cent of specimens positive for VIP were from patients presenting with headache. There was no statistically significant association between the presence of VIP-IR and headache (chi(2) = 0.077, P = 0.781). CONCLUSION: Although the significance of VIP positivity in pituitary tumour-associated headache is unknown it seems unrelated to headache. It remains possible that the mechanism of these headaches relates to the production of either an as yet unidentified peptide, or a combination of nociceptive peptides.
Biomarkers↗
Verapamil induced gingival enlargement in cluster headache.
Verapamil is an effective prophylactic treatment for cluster headaches and, therefore, is widely used. This report describes four patients with cluster headache who developed gingival enlargement after initiating treatment with verapamil. In two patients, it was possible to control this side effect adequately by optimising oral hygiene and dental plaque control. In the other two patients, lowering of the verapamil dose, in addition to optimal oral hygiene and dental plaque control, was necessary; in one patient verapamil had to be stopped completely to reverse the gingival enlargement. Doctors treating cluster headache with verapamil need to be aware of this side effect, especially as it may be preventable with good dental hygiene and dental plaque control, is reversible with reduction or cessation of verapamil, and can lead to dental loss.
Adult↗