Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of non-familial hemiplegic migraine are described. Naloxone reversed the neurological deficits accompanying attacks, whereas the pain was uninfluenced. The possibility that the opiate-antagonist naloxone facilitates regression of neurological symptoms associated with migraine attacks in general is voiced.
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PMID:Non-familial hemiplegic migraine responsive to naloxone. 687 87

Migraine is an inheritable disease, and the mutation causing a rare variant of migraine (familial hemiplegic migraine) has now been demonstrated. The mutated gene encodes a subunit of a brain-specific calcium channel in cell membranes. Brains of patients with recurrent migraine attacks seem to behave differently from other brains, also when examined outside attacks, in that they commonly demonstrate lack of habituation when exposed to serial stimuli. The patho-physiological process of the attack might well consist of a spreading cortical depression starting in the occipital region and gradually involving other parts of the cortex. It is primarily a cerebral process secondarily accompanied by reduced cerebral blood flow, later converting into increased flow. The pain of migraine probably is mediated by way of the trigeminal nerve which releases vasoactive peptides leading to dilatation of the greater blood vessels. During an attack there is increased metabolism in cranial parts of the brain stem, demonstrated as areas of increased blood flow in PET studies. This increased metabolism persists even when the symptoms of migraine have disappeared after drug treatment, perhaps because the migraine attacks may be generated in this region. The primary dysfunction in migraine probably is located in the brain rather than in blood vessels.
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PMID:[Current viewpoints on etiology and physiopathology of migraine]. 1035 52

The term "migrant variant" is not used in the headache classification of the International Headache Society (IHS), but it includes those forms of migraine that are not typical of migraine with or without aura. Headaches that do not quite fulfill all of the IHS criteria are termed "migrainous disorder." Migraine associated with auras arising from unusual sites includes basilar migraine, retinal migraine, and ophthalmoplegic migraine. Two of the chromosomal sites for hemiplegic migraine have been identified. Migraine aura may occur without headache and an aura may be prolonged. Migrainous infarct has occurred when the aura lasts more than 1 week or imaging studies are positive and other etiologies have been ruled out. If the migraine attack is prolonged beyond 3 days the term "status migrainousus" is applied.
Curr Pain Headache Rep 2001 Apr
PMID:Migraine variants. 1125 50

The discovery of mis-sense mutations in the alpha1A subunit of the P/Q-type calcium channel in patients with familial hemiplegic migraine indicates the potential involvement of dysfunctional ion channels in migraine. The periaqueductal gray (PAG) region of the brainstem modulates craniovascular nociception and, through its role in the descending pain modulation system, may contribute to migraine pathophysiology. In this study we sought to investigate the possible link between the genetic mutations found in migraineurs and the PAG as a modulator of craniovascular nociception. We microinjected the P/Q-type calcium-channel blocker omega-agatoxin IVA into the rat ventrolateral PAG (vlPAG). We examined its effect on the nociceptive transmission of second-order neurons recorded in the trigeminal nucleus caudalis and activated by stimulation of the parietal dura mater. After injection of agatoxin into the vlPAG (n = 20) responses to dural stimulation were facilitated by 143% (p < 0.0001) for Adelta-fiber activity and 180% for C-fiber activity (p < 0.05). Similarly, spontaneous background activity increased by 163% (p < 0.0001). These results demonstrate that P/Q-type calcium channels in the PAG play a role in modulating trigeminal nociception and suggest a role for dysfunctional P/Q-type calcium channels in migraine pathophysiology.
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PMID:P/Q-type calcium-channel blockade in the periaqueductal gray facilitates trigeminal nociception: a functional genetic link for migraine? 1188 May 34

THE ROLE OF IONIC CHANNEL DYSFUNCTION: During various neurological diseases has been evoked for many years on electro-physiological data. Molecular biology has led to great progress in neurology, and can be considered "functional" since it is surpasses the classical anatomo-clinical methods. IONIC CHANNEL DYSFUNCTION: Can be determined genetically, resulting from the mutation of a gene code of a channel sub-unit. CHANNELOPATHIES ARE RESPONSIBLE: For muscular diseases (myotonia, familial periodic paralysis, malignant hyperthermia and congenital myasthenia), but also for central nervous system disorders such as familial hemiplegic migraine, hereditary paroxystic ataxia and certain forms of Mendel's law hereditary epilepsy. ACQUIRED IONIC CHANNEL DYSFUNCTION: Resulting from auto-immune aggression is implied in diseases such as Lambert-Eaton's myasthenic syndrome and Isaac's neuromyotonia syndrome. It probably plays a part in the clinical, and particularly the sensitive expression (paresthesia and pain) of some peripheral neuropathies and certain central nervous system affections, such as multiple sclerosis.
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PMID:[Ion channel abnormalities ("channelopathies") in neurologic diseases]. 1188 65

Migraine is a common episodic headache disorder. A comprehensive headache treatment plan includes acute attack treatment to relieve pain and impairment and long-term preventive therapy to reduce attack frequency, severity, and duration. Circumstances that might warrant preventive treatment include: (i) migraine that significantly interferes with the patient's daily routine despite acute treatment; (ii) failure, contraindication to, or troublesome side-effects from acute medications; (iii) overuse of acute medications; (iv) special circumstances, such as hemiplegic migraine; (v) very frequent headaches (more than two a week); or (vi) patient preference. Start the drug at a low dose. Give each treatment an adequate trial. Avoid interfering, overused, and contraindicated drugs. Re-evaluate therapy. Be sure that a woman of childbearing potential is aware of any potential risks. Involve patients in their care to maximize compliance. Consider co-morbidity. Choose a drug based on its proven efficacy, the patient's preferences and headache profile, the drug's side-effects, and the presence or absence of coexisting or co-morbid disease. Drugs that have documented high efficacy and mild to moderate adverse events (AEs) include beta-blockers, amitriptyline, and divalproex. Drugs that have lower documented efficacy and mild to moderate AEs include selective serotonin reuptake inhibitors (SSRIs), calcium channel antagonists, gabapentin, topiramate, riboflavin, and non-steroidal anti-inflammatory drugs.
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PMID:Migraine: preventive treatment. 1537 26

The field of migraine genetics has seen an explosion of information over the last year. In a recent breakthrough, missense mutations in a chromosome 1q23 gene, ATP1A2, encoding a Na+, K+-ATPase, have been identified in four distinct pedigrees with a rare form of familial hemiplegic migraine (FHM). ATP1A2 is expressed in the brain, like the voltage gated calcium channel gene, CACNA1A, previously identified as the first hemiplegic migraine gene (FHM1). The shared hemiplegic migraine phenotype of mutations in ATP1A2 and CACNA1A raises the possibility that they coordinately regulate ion homeostasis that determines susceptibility to the initiation of both migraine aura and the pain phase of migraine. For the more common and genetically complex forms of migraine, genome-wide screens have identified several new loci on 4q24, 6p12.2-21.1, 11q24, and 14q21.2-q22.3, suggesting additional migraine genes in these regions. In addition, a recent large case-control association study has linked single nucleotide polymorphisms in the insulin receptor/INSR gene with migraine. However, these polymorphisms do not result in detectable changes in receptor function. The continuing genetic identification of key proteins involved in migraine will refine our understanding of this common and sometimes debilitating disorder, which can strike during the most productive years of a person's life. Given the co-morbidity of migraine with depression and bipolar disorder, our knowledge of the causes of migraine may also contribute to our understanding of these disorders.
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PMID:Update on the genetics of migraine. 1462 54

Hemiplegic migraine may be familial or sporadic. Both forms share a similar spectrum of clinical presentations and genetic heterogeneity. Current data support the concept that sporadic and familial cases should be thought of as similar, but separate disorders. Sporadic cases are more difficult to diagnose and often require several investigations to rule out more ominous possibilities. Therapeutic options are limited, but future genetic research may elucidate pathophysiologic mechanisms that may, in turn, yield more specific treatments.
Curr Pain Headache Rep 2004 Jun
PMID:Sporadic hemiplegic migraine. 1511 42

Inhibitory synapses play key roles in the modulatory circuitry that regulates pain signaling and generation of migraine headache. A rare, dominant form of this common disease, familial hemiplegic migraine type 1 (FHM1), arises from missense mutations in the pore-forming alpha1A subunit of P/Q-type Ca2+ channels. These channels are normally vital for presynaptic Ca2+ entry and neurotransmitter release at many central synapses, raising questions about effects of FHM1 mutations on neuronal Ca2+ influx and inhibitory and excitatory neurotransmission. We have expressed the four original FHM1 mutant channels in hippocampal neurons from alpha1A knockout mice. Whole-cell recordings indicated that FHM1 mutant channels were less effective than wild-type channels in their ability to conduct P/Q-type current, but not generally different from wild type in voltage-dependent channel gating. Ca2+ influx triggered by action potential waveforms was also diminished. In keeping with decreased channel activity, FHM1 mutant channels were correspondingly impaired in supporting the P/Q-type component of inhibitory neurotransmission. When expressed in wild-type inhibitory neurons, FHM1 mutant channels reduced the contribution of P/Q-type channels to GABAergic synaptic currents, consistent with a competition of mutant and endogenous channels for P/Q-specific slots. In all cases, N-type channels took up the burden of supporting transmission and homeostatic mechanisms maintained overall synaptic strength. The shift to reliance on N-type channels greatly increased the susceptibility to G protein-coupled modulation of neurotransmission, studied with the GABAB agonist baclofen. Thus, mutant-expressing synapses might be weakened in a heightened state of neuromodulation like that provoked by triggers of migraine such as stress.
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PMID:Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type Ca2+ channel activity and inhibitory synaptic transmission. 1569 44

A combination of basic science and human physiology, particularly functional neuroimaging, has radically altered our understanding of migraine with a focus on brain mechanisms for this common and disabling disorder. Genetic studies have begun to provide plausible targets for the basic molecular defect in terms of ion channels, albeit thus far in the rare condition of familial hemiplegic migraine (FHM). Migraine pathophysiology involves the trigeminovascular system and central nervous system modulation of the pain-producing structures of the cranium. The degree to which head pain results from the activation of the nociceptors of pain-producing intracranial structures, or to the facilitation or lack of inhibition of afferent signals, is not clear at this time. An understanding of the pain mechanism is likely to provide insights into the mechanisms underlying the more generalized sensory dysfunction that is so typical of migraine.
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PMID:Migraine pathophysiology. 1583 86


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