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

The trigeminal nerve transmits headache pain from blood vessels of the pia mater and dura mater. Triggers for this pain are not well understood, but probably are multiple and largely chemical and develop within the brain parenchyma, the blood vessel wall, and the blood itself. These unknown triggers stimulate the trigeminovascular axons, causing pain and releasing vasoactive neuropeptides from perivascular axons. Released neuropeptides activate endothelial cells, mast cells, and platelets to then increase extracellular levels of amines, arachidonate metabolites, peptides, and ions. Hyperalgesia and prolongation of pain develop as a consequence, mediated by products from activated cells and injured tissue. Within postsynaptic brain stem neurons of the trigeminal nucleus caudalis, trigeminovascular activation stimulates the expression of an early immediate response gene c-fos. Both neurogenic inflammation and c-fos expression are blocked by sumatriptan and ergot alkaloids via prejunctional mechanisms involving putative 5-HT receptors closely related to the 5-HT1D subtype on trigeminovascular fibers. The mechanisms of action of sumatriptan and ergot alkaloids described herein are unrelated to the nature of the migraine trigger or to the contractile state of vascular smooth muscle.
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PMID:Neurogenic inflammation in the pathophysiology and treatment of migraine. 838 8

The headache phase of the migraine attack is thought to be associated with a dilation of cranial blood vessels, particularly those in the dura mater, and an accompanying localized sterile inflammatory response. Serotonin, or 5-hydroxytryptamine (5-HT), is considered a possible mediator of this syndrome. Receptors for 5-hydroxytryptamine are present in cranial arteries and are widely distributed in the CNS. Studies indicate that sumatriptan, a 5-HT1 receptor agonist, is effective in treating acute migraine attacks. The mechanism of sumatriptan's therapeutic action is not completely understood. Evidence from animal and human studies suggests that sumatriptan constricts dural vessels and inhibits neuropeptide release from trigeminal nerve endings by activating 5-HT1 receptors. Clinically, sumatriptan is rapidly effective against all features of the headache phase in migraine in up to 80% of patients. The headache may recur, however, within 24 hours in about one third of patients, but this can be treated effectively with a subsequent dose of sumatriptan. Treatment with sumatriptan has been well tolerated with only minor, transient, acute side effects reported. At present, only limited information is available regarding long-term tolerability, safety, and efficacy. Sumatriptan should not be prescribed to patients with a cardiovascular history.
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PMID:Sumatriptan in the treatment of migraine. 838 11

Migraine patients have chronically low systemic 5-HT, predisposing them to develop migrainous headache once an attack has been initiated. Changes in platelet 5-HT content are not causally related, but reflect similar changes at a neuronal level. Stimulation of vascular 5-HT1 receptors, probably located in the vessel wall within the dural vascular bed, may alleviate the headache and associated symptoms, but does not interact with earlier mechanisms within the pathophysiological cascade. These receptors are of an as yet unidentified 5-HT1 subtype, closely resembling, but not identical to 5-HT1D receptors. Activation of these receptors results in vasoconstriction, inhibiting depolarization of sensory perivascular afferents within the trigemino-vascular system and thus stopping the headache. Additional inhibition of the release of vasoactive neuropeptides may be involved, but seems to be of only secondary clinical importance.
Cephalalgia 1993 Jun
PMID:On serotonin and migraine: a clinical and pharmacological review. 839 42

The aim of this study was to investigate the effect of the anti-migraine drug and selective 5-HT1 receptor agonist, sumatriptan, on membrane potential of guinea-pig isolated trigeminal ganglion. Ganglia were divided into three longitudinally, placed in two-compartment baths and the d.c. potential between compartments was recorded extracellularly. Drugs were applied to the Krebs superfusion fluid of one compartment. KCl (3 mmol/l) and GABA (0.1 mmol/l) caused depolarization (0.30 +/- 0.05 and 0.55 +/- 0.08 mV respectively, n = 11-19). 5-HT (1-10 mumol/l) caused small depolarizations (0.06 +/- 0.02 mV, n = 8) but sumatriptan (0.1-10 mumol/l) had no effect on trigeminal ganglion membrane potential. Collagenase pretreatment, to enhance desheathing, or modification of the composition of the Krebs solution failed to reveal any effect of sumatriptan. These data provide no evidence to suggest that sumatriptan inhibits neurotransmission in trigeminal ganglion. However, 5-HT1 receptors may be present in insufficient numbers in the trigeminal ganglion to elicit a change in membrane potential. Further studies are required to investigate the effect of sumatriptan at the level of the sensory nerve terminals within the intracranial vasculature, where 5-HT1 receptors may be concentrated.
Cephalalgia 1993 Jun
PMID:Extracellular recordings of membrane potential from guinea-pig isolated trigeminal ganglion: lack of effect of sumatriptan. 839 43

Exteroceptive suppression of temporalis muscle activity was studied in patients with chronic headache and in healthy controls. Among different methods of recording, averaging 10 full-wave rectified EMG responses produces results with acceptable variability and discomfort. The late temporalis exteroceptive suppression period (ES2) is reduced on average in patients with chronic tension-type headache; this finding has been reproduced by several independent laboratories. Mean duration of temporalis ES2 is also diminished, but to a lesser degree, in daily drug abuse headache and, as shown by others, in episodic tension-type headache. It is normal in migraine between attacks, cluster headache and various types of symptomatic headaches. Temporalis ES2 may be decreased in untreated patients with major depression. In healthy volunteers, temporalis ES2 duration is reduced by a short-lasting painful stimulus to peripheral limbs after a delay of 50 to 60 ms, and by a sub-motor threshold electromagnetic stimulation to the contralateral cerebral cortex after a delay of 20 to 30 ms. In contrast, long-lasting trains of peripheral painful stimuli have no effect. Various pharmacological agents are able to modify temporalis ES2. Its duration is increased by 5-HT antagonists, but decreased by 5-HT uptake blockers. Pharmacological effects may differ between controls and patients. Considering these results and available data on the anatomo-functional organization of masticatory reflexes, we postulate that temporalis ES2 is a marker of the excitability of interneuronal nets in the ponto-medullary reticular formation. In chronic tension-type headache, excitability of these interneurons is decreased because of inadequate control by the serotonergic raphe magnus nucleus and the periaqueductal gray matter. Dysfunctioning of the latter structures might be caused by abnormal limbic inputs to the brain stem. Some steps of this pathophysiological hypothesis can be verified by modern neurophysiological techniques.
Headache 1993 Jan
PMID:Wolff Award 1992. Exteroceptive suppression of temporalis muscle activity in patients with chronic headache and in normal volunteers: methodology, clinical and pathophysiological relevance. 843 96

In recent years studies of the suppression of EMG activity in temporalis muscle induced by stimulation in the trigeminal territory have opened new perspectives in headache research. The various methods that have been used in different laboratories are reviewed and some of the physiological modulations of temporalis exteroceptive suppression are described. Among different methods of recording, averaging 10 full-wave rectified EMG responses produces results with acceptable variability and discomfort. In order to obtain maximal responses the intensity of the stimulation should reach at least 20 mA. To avoid habituation of the second temporalis exteroceptive suppression period (ES2), the stimulation frequency has to be at 0.1 Hz or below. The level of voluntary contraction is not a critical variable as long as it reaches 50% of maximum. Some physiological variations of temporalis suppression are well documented. In females, ES2 is shorter during menstruation than at mid-cycle and correlated with the estradiol/progesterone ratio in plasma. Conditioning temporalis ES2 by a preceding peripheral stimulus markedly reduces its duration, which is partly reversible by naloxone. Various pharmacological agents are able to modify temporalis ES2: its duration is increased by 5-HT1 antagonists, but decreased by 5-HT uptake blockers; contradictory results have been obtained with acetylsalicylic acid. These results suggest that inhibitory brain-stem interneurons mediating temporalis ES2 are inhibited by serotonergic afferents, probably from the raphe magnus nucleus, and that the latter receives an excitatory input from the periaqueductal gray matter and other limbic structures, in part via opioid receptors.
Cephalalgia 1993 Feb
PMID:Exteroceptive suppression of temporalis muscle activity: methodological and physiological aspects. 844 85

Migraine is a neurovascular reaction to sudden changes in the internal or external environment. Each individual has a hereditary "migrainous threshold," with the degree of susceptibility depending on the balance between excitation and inhibition at various levels of the nervous system. The mechanism of migraine has been presented as an unstable trigeminovascular reflex with a segmental defect in the pain control pathway. This defect permits excessive discharge of part of the spinal nucleus of the trigeminal nerve and its thalamic connections in response to excessive afferent input or corticobulbar drive. The end result is the interaction of brain stem and cranial blood vessels, with the afferent impulses from the latter creating the throbbing (pulsating) character of the headache. Diffuse projections from the locus ceruleus to the cerebral cortex could initiate cortical oligemia and possibly spreading depression. Activity in this system could account for the migrainous aura that may occur quite independently of the headache. The headache phase may be interrupted by therapy aimed at either the central or peripheral end of the trigeminovascular afferent pathway. Strong evidence suggests that serotonin (5-hydroxytryptamine, 5-HT) plays an important part in the genesis of migraine. Whether 5-HT is effective in central pain control pathways, the serotonergic projection to the cerebral cortex, its direct action on the cranial blood vessels, or its action at all three sites remains uncertain. It seems probable that the 5-HT agonists act to terminate migraine through the cerebral and extracranial circulations, whereas medications used for prophylaxis may act centrally.
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PMID:Current concepts of migraine pathogenesis. 850 82

1. m-Chlorophenylpiperazine (m-CPP), a 5-HT1c-receptor agonist, induces migraine-like headaches when taken orally by migraine sufferers. The present study was undertaken to see what effects m-CPP had on 5-HT function in platelets. 2. Platelets from healthy male volunteers were loaded with [3H]-5-HT and continuously perfused in vitro with carboxygenated Krebs solution at 37 degrees C. After 30 min washout the effects of m-CPP, thrombin, 5-HT and ADP on the efflux of [3H]-5-HT were recorded. 3. m-CPP (0.5-500 microM) did not evoke an increase in the efflux of [3H]-5-HT over that occurring spontaneously whereas thrombin, unlabelled 5-HT and ADP did. The effects of 5-HT were potentiated by ADP. The results were identical whether or not the 5-HT reuptake blocker paroxetine (1 microM) was present. 4. m-CPP inhibited the increase in the efflux of [3H]-5-HT evoked by different concentrations of unlabelled 5-HT in the presence of ADP (2.5 microM) and displaced the 5-HT log concentration response curve to the right. A similar result was obtained with the 5-HT2-receptor antagonist ketanserin. 5. We conclude that m-CPP is a 5-HT2-receptor antagonist on human platelets, which is unlikely to account for its headache-inducing property, as many drugs effective in migraine prophylaxis have this action.
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PMID:The effects of 5-HT and m-chlorophenylpiperazine (m-CPP) on the efflux of [3H]-5-HT from human perfused platelets. 851 59

Approximately 12% of the population suffers from migraine. This sudden, usually unbearable headache can last for up to 72 hours and can be accompanied by vegetative symptoms. Prophylactic treatment is recommended if more than three attacks of headache occur monthly. For prophylactic therapy, beta-blockers or the calcium antagonist flunarizine are mostly used. Serotonin blockers, which have undesirable side-effects, and dihydroergotamine, which can only be used for a short time as well as non-steroidal antirheumatics and antidepressants and relaxation exercises are used more rarely. The literature reports on the successful treatment of migraine with acupuncture. Although none of the studies made to date fulfil the necessary quality criteria, there is no doubt about the efficacy of acupuncture in the treatment of migraine. Acupuncture therapy only makes sense if it reduces the patient's discomfort and the taking of drugs.
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PMID:[Value of acupuncture in treatment of migraine]. 865 39

During the last decade, numerous studies have been carried out to explore the function of the immune system in cluster headache and the release of reciprocal informational molecules from pain-sensitive structures. These neuroimmunological findings in cluster headache syndrome, although carefully considered, have varied from genetic aspects (HLA antigens) to functional activity of the immune system (NK cytotoxicity), and from study of the receptor expression of classical neurotransmitters of pain (5-HT, histamine) on immunocompetent cells, to the study of cytokines with a potent pro-inflammatory activity (interleukin-1). Other aspects considered have ranged from the study of the effectiveness of substances possessing a wellknown activity on the immune system (prednisone, lithium carbonate) in shortening cluster attacks to the 5-HT receptor expression changes observed on a peripheral substrate (monocytes) after the administration of sumatriptan. Although this was an exciting area of pioneering research, we have always interpreted our findings cautiously. In summary, we now believe that the neuroimmunological aspects of cluster headache can be proposed as an integrative model and that this immunological mechanism could improve our understanding of the pathogenic basis for this still obscure disease.
Headache 1996 May
PMID:Putative neuroimmunological mechanisms in cluster headache. An integrated hypothesis. 868 73


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