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

Four percent to 5% of the general population suffers from chronic daily or near daily headache. A majority of them are chronic migraine (transformed migraine), and the rest are chronic tension-type headaches. Prophylactic treatments of migraine and chronic tension-type headache are far from satisfactory because of lack of good efficacy, intolerable side effects, development of tachyphylaxis over long-term use, and drug interactions. Comorbidities and analgesic overuse complicate matters further. There has been an increasing search for more effective treatment for chronic headache, which would result in "modification of the disease." Botulinum toxin type A is an emerging treatment for such patients whose headaches are poorly controlled with currently available prophylactic pharmacotherapy or in patients who do not tolerate them and are unable to continue them. Contraindications to acute migraine therapy such as triptans may also be an indication for alternative treatments like botulinum toxin type A. A number of double blind and open-label trials have been done for migraine and chronic tension-type headache. Although some of the well designed double blind, placebo-controlled, randomized clinical trials are in progress, it has been the clinical experience of many physicians that botulinum toxin type A cuts down the frequency and severity of headaches, improves disability scales, improves quality of life, and reduces the need for acute medications. Repeated use of botulinum toxin type A is needed to sustain long-term improvement, and long-term results indicate lack of tachyphylaxis in the majority of patients. Botulinum toxin type A is well tolerated and totally free of many long-term side effects, which are seen with other prophylactic agents. The clinician may be well advised to consider botulinum toxin type A in the most refractory forms of chronic headaches including chronic migraine and chronic tension-type headache. Appropriate injection techniques, selection of injection sites, and appropriate doses are necessary for success.
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PMID:The Use of Botulinum Toxin Type A in Headache Treatment. 1216 25

Botulinum toxin type A, a protein long used in the successful treatment of various dystonias, has a complex mechanism of action that results in muscle relaxation. At the neuromuscular junction, the presynaptic nerve ending is packed with synaptic vesicles filled with acetylcholine, and clustered at the tip of the folds of the postsynaptic muscle membrane are the acetylcholine receptors. Synaptic vesicles fuse with the membrane in response to an elevation of intraneuronal calcium concentration and undergo release of their transmitter by exocytosis. Intracellular proteins that contribute to the fusion of the vesicles with the plasma membrane during exocytosis include synaptosomal protein with a molecular weight of 25 kDa (SNAP-25); vesicle-associated membrane protein (VAMP), also known as synaptobrevin; and syntaxin. Through their proteolytic action on these proteins, botulinum toxins prevent exocytosis, thereby inhibiting the release of acetylcholine. There are 7 serotypes of this toxin-A, B, C1, D, E, F, and G-and each cleaves a different intracellular protein or the same target at distinct bonds. The separate cleavage sites in SNAP-25 for botulinum toxin types A and E contribute to their dissimilar durations of muscle relaxation. This report describes the molecular basis for the inhibition by botulinum toxins of neuroexocytosis and subsequent functional recovery at the neuromuscular junction.
Headache
PMID:Synaptic transmission: inhibition of neurotransmitter release by botulinum toxins. 1288 90

Botulinum toxin type A, a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction including cervical dystonia, blepharospasm, and hemifacial spasm. It inhibits neuromuscular signaling by blocking the release of acetylcholine at the neuromuscular junction. The biological effects of the toxin are transient, with normal neuronal signaling returning within approximately 3 to 6 months postinjection. Recent clinical findings suggest that botulinum toxin type A may inhibit pain associated with migraine and other types of headache. However, the mechanism by which this toxin inhibits pain is not fully understood and is under investigation. Research findings suggest that botulinum toxin type A inhibits the release of neurotransmitters from nociceptive nerve terminals and, in this way, may possess an analgesic effect. A number of retrospective open-label chart reviews and 3 double-blind, placebo-controlled trials have demonstrated that localized injections of botulinum toxin type A significantly reduce the frequency, severity, and disability associated with migraine headaches. Although the majority of patients in these studies experienced no botulinum toxin type A-mediated side effects, a small percentage of patients did report transient minor side effects including blepharoptosis, diplopia, and injection-site weakness. Currently, 4 randomized, placebo-controlled, clinical trials are being conducted to evaluate the efficacy, optimal dosing, and side-effect profile of botulinum toxin type A as a novel treatment for migraine and other types of headache. These studies may provide further evidence that botulinum toxin type A is an effective option for the preventive treatment of migraine.
Headache
PMID:Botulinum neurotoxin for the treatment of migraine and other primary headache disorders: from bench to bedside. 1288 91

The objective of this study was to evaluate the efficacy and safety of botulinum toxin type A for the treatment of glabellar lines. Patients with moderate or severe glabellar lines at maximal frown received intramuscular injections of placebo or 20 U of botulinum toxin type A (Botox; Allergan, Inc., Irvine, Calif.) distributed among five injection sites (one in the procerus muscle and two in each corrugator supercilii). Follow-up assessments were performed at 7, 30, 60, 90, and 120 days after injections. Efficacy measures were the physician's rating of glabellar line severity at maximal frown and at rest (none, mild, moderate, or severe) and the patient's global assessment of changes in glabellar lines, from +4 (100 percent better) to -4 (100 percent worse). A total of 273 patients were enrolled (botulinum toxin, 202 patients; placebo, 71 patients). All except five patients (botulinum toxin, two patients; placebo, three patients) completed the study. For the physician's rating at maximal frown, the responder rate (percentage of patients with severity ratings of none or mild in follow-up evaluations) for the botulinum toxin group peaked at 77 percent at day 30 and was significantly greater than that for the placebo group at every follow-up visit (p < 0.001). For the patient's assessment, the responder rate (percentage of patients with scores of +2 or more) for the botulinum toxin group peaked at 89 percent at day 30 and was significantly greater than that for the placebo group at every follow-up visit (p < 0.001). Rates of adverse events were similar for the two groups. The only adverse event with an incidence of >/=5 percent was headache (botulinum toxin, 11 percent; placebo, 20 percent). The incidence of blepharoptosis was 1 percent for the botulinum toxin group. Botulinum toxin type A was remarkably safe and effective in reducing glabellar lines.
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PMID:Double-blind, placebo-controlled study of the safety and efficacy of botulinum toxin type A for patients with glabellar lines. 1297 29

Botulinum toxin type A (BoNT-A) produced by the bacterium Clostridium botulinum is a potent inhibitor of acetylcholine release in the neuromuscular junction and has been used to treat many disorders related to excessive muscle contraction. However, BoNT-A has recently been used in pain therapy to treat myofascial pain, low back pain and various types of headaches, including migraine. The purpose of this study is to investigate the antinociceptive effect of BoNT-A and its underlying mechanism in the rat formalin inflammatory pain model. BoNT-A (3.5, 7, 15 and 30 U/kg) or vehicle was administered to the plantar surface of the right hindpaw of male Sprague-Dawley rats. BoNT-A dose-dependently (P<0.05) inhibited formalin-induced nociceptive behavior during phase 2 but not during phase 1 when administered 5 h to 12 days before formalin challenge. The onset of the antinociceptive effect started at 5 h after pre-treatment and this effect lasted for at least 12 days. BoNT-A (7 U/kg) also reduced edema. Consistent with the lack of effect in the formalin phase 1, BoNT-A, at 15 U/kg, had no effect on acute thermal nociception; no local muscle weakness was observed at this dose. Pre-treatment of rats with BoNT-A (3.5, 7 or 15 U/kg) all significantly reduced formalin-evoked glutamate (Glu) release. These results demonstrate that local peripheral injection of BoNT-A significantly reduces formalin-induced nociceptive behaviors with the absence of obvious muscle weakness. Such an antinociceptive effect of BoNT-A is associated with the inhibition of formalin-induced release of Glu (and/or neuropeptides) from primary afferent terminals.
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PMID:Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. 1471 98

Botulinum toxins are, as a group, among the most potent neuromuscular toxins known, yet they are clinically useful in the management of conditions associated with muscular and glandular over-activity. Botulinum toxins act by preventing release of acetylcholine into the neuromuscular junction. While botulinum toxin type A is commonly available, different manufacturers produce specific products, which are not directly interchangeable and should not be considered as generically equivalent formulations. Type B is also available in the market. Each formulation of botulinum toxin is unique with distinct dosing, efficacy and safety profiles for each use to which it is applied. Botulinum toxin type A is the treatment of choice based on its depth of evidence in dystonias and most other conditions. Botulinum toxin type A is established as useful in the management of spasticity, tremors, headache prophylaxis and several other neurological conditions. Active research is underway to determine the parameters for which the type B toxin can be used in these conditions, as covered in this review. Botulinum toxin use has spread to several fields of medicine.
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PMID:Botulinum toxins: pharmacology and its current therapeutic evidence for use. 1474 21

Botulinum toxin type A (Botox) is increasingly used in the management of migraine and tension-type headaches. The results from small placebo-controlled trials and extensive open-label experience has suggested a significant role for this neurotoxin in the management of refractory headache. Several large placebo-controlled trials of episodic and chronic migraine are currently underway.
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PMID:Botulinum toxin type A (Botox) in the treatment of migraine and other headaches. 1585 12

Botulinum toxin type A (BTX-A) is best known to neurologists as a treatment for neuromuscular conditions such as dystonias and spasticity and has recently been publicized for the management of facial wrinkles. The property that makes botulinum toxin type A useful for these various conditions is the inhibition of acetylcholine release at the neuromuscular junction. Although botulinum toxin types A and B (BTX-A and BTX-B) continue to find new uses in neuromuscular conditions involving the somatic nervous system, it has also been recognized that the effects of these medications are not confined to cholinergic neurons at the neuromuscular junction. Acceptors for BTX-A and BTX-B are also found on autonomic nerve terminals, where they inhibit acetylcholine release at glands and smooth muscle. This observation led to trials of botulinum neurotoxins in various conditions involving autonomic innervation. The article reviews the emerging use of botulinum neurotoxins in these and selected other conditions, including sialorrhea, primary focal hyperhidrosis, pathological pain and primary headache disorders that may be of interest to neurologists and related specialists.
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PMID:Expanding use of botulinum toxin. 1599 Jan 16

Migraine is a common neurological disorder, characterized by recurrent attacks of severe headache. Its prevalence is estimated 8.4% of general population in Japan. Acute migraine treatment has dramatically improved with the development of a novel class of selective 5-HT1B/1D/1F receptor agonists, known as the triptans, but prophylactic treatment still remains limited. Botulinum toxin type A(BoNT-A) has recently been shown to be effective in randomized control trials, but no prospective study has been conducted yet in Japan. In this paper, we review the results of recently published controlled trials, touching on its methodology, optimal dose, patient selection, and possible mechanisms, as well as on going clinical trial in our university.
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PMID:[Prophylactic treatment with botulinum toxin type A]. 1621 96

Migraine is a common and debilitating disorder that often requires prophylactic therapy, particularly for those migraine patients who meet the diagnostic criteria for chronic daily headache (chronic migraine). Existing prophylactic treatments for migraine are inadequate for many patients due to their modest efficacy and/or systemic side effects. Alternative treatment strategies are needed, particularly in those with chronic migraine. Botulinum toxin type A is a locally injected protein complex that has been investigated as a treatment for episodic migraine and chronic daily headache. A systematic series of controlled trials has led to the identification of a subset of migraineurs with chronic daily headache who obtain demonstrated benefits of botulinum toxin type A over placebo that is maintained with repeated treatments.
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PMID:Botulinum toxin type A for the treatment of migraine. 1672 18


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