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

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

Clinical data and experience to date have demonstrated that BoNT-A is an effective and well-tolerated therapy for the prevention of migraine and other headache disorders. It has a long duration of action that may last over 4 months with no systemic or serious AEs. Several issues remain to be defined, however, including dosing, location, and number of injections; optimal dilution of BoNT-A; specific headache types that respond best to BoNT-A; and long-term efficacy and safety. Data from ongoing well-designed trials that include a larger patient population investigating these issues may confirm a role for BoNT-A as a first-line agent for migraine prevention. Neurotoxin therapy is part of a broader headache management approach. Because the injection techniques for headache are unique and vary depending on the primary headache disorder being treated and the location and pattern of pain referral, the use of BoNT-A for headache is not simply an extension of its use for cosmesis. The use of BoNT-A in the overall management of primary headache disorders should be reserved for medical practitioners who not only have experience with BoNT-A injections, but possess the expertise in the diagnosis and management of complex headache disorders. Educating patients and addressing headache triggers and optimizing acute treatment improve the outcome of any preventive program.
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PMID:Botulinum neurotoxin for the treatment of migraine and other primary headache disorders. 1522 77

Botulinum toxin type A (BoNT-A) has been recently suggested as prophylaxis therapy for the treatment of primary headache chronic forms. Several studies on its efficacy are available, but results are often contradictory and not univocal. The effects of BoNTA on chronic forms of both tension- type headache and migraine have been investigated. In this study we introduce our five-year long experience with BoNT-A (Botox, Allergan, Irvine, CA). The employed dosage was 100 U and the Fixed Sites-Fixed Doses (FSFD) protocol was used. The period of study was April 2001 to July 2006. A sum of 1347 patients suffering from chronic daily headache (CDH) were treated. We registered in these patients the number of headache days per month and observed their reduction in relation to the number of injections. The best results were found after 12 months of treatment, with patients being free of attacks 23 days per month. The BoNT-A treatment was safe and well tolerated, as only 1.6% of patients reported adverse events, and they were all mild and transient. In conclusion, BoNT-A therapy appears to be an efficacious new therapeutic choice in the prophylaxis of CDH, especially for patients not responding to previous prophylactic treatments.
J Headache Pain 2006 Dec
PMID:Long-term benefits of botulinum toxin type A (BOTOX) in chronic daily headache: a five-year long experience. 1714 65

The objective of this study was to investigate the long-term efficacy and safety of botulinum toxin type-A (BoNT-A) for refractory chronic tension-type headache (CTTH). An open-label, prospective study was carried out in the Department of Neurology of Kirikkale University on 28 patients (8 males, 20 females), mean age 35.6 years, diagnosed with moderate/severe CTTH refractory to preventive medications. Each patient received BoNT-A injections once in pericranial muscles. Efficacy and safety data were analysed for 28 refractory CTTH patients who were receiving concomitant headache prophylactic medications at baseline and during the study. The main outcome parameters were reduction of headache frequency and intensity over 1 year. Both parameters were significantly decreased (p<0.05) by the end of the study. Sixty-four percent of patients reported complete headache relief at the final visit, compared to 7% CTTH persisted. BoNT-A also resulted in significant reductions in analgesic consumption (p<0.05). Adverse effects were transient and local. BoNT-A was found to be an effective and safe treatment for refractory CTTH patients with concomitant headache prophylactic medications, resulting in significant reductions in headache frequency, intensity and analgesic consumption which persisted up to 1 year.
J Headache Pain 2007 Oct
PMID:The long-term efficacy and safety of botulinum toxin in refractory chronic tension-type headache. 1795 70

Persistent occipital neuralgia can produce severe headaches that are difficult to control by conservative or surgical approaches. We retrospectively describe a series of six patients with severe occipital neuralgia who received conservative and interventional therapies, including oral antidepressants, membrane stabilizers, opioids, and traditional occipital nerve blocks without significant relief. This group then underwent occipital nerve blocks using the botulinum toxin type A (BoNT-A) BOTOX Type A (Allergan, Inc., Irvine, CA, U.S.A.) 50 U for each block (100 U if bilateral). Significant decreases in pain Visual Analog Scale (VAS) scores and improvement in Pain Disability Index (PDI) were observed at four weeks follow-up in five out of six patients following BoNT-A occipital nerve block. The mean VAS score changed from 8 +/- 1.8 (median score of 8.5) to 2 +/- 2.7 (median score of 1), while PDI improved from 51.5 +/- 17.6 (median 56) to 19.5 +/- 21 (median 17.5) and the duration of the pain relief increased to an average of 16.3 +/- 3.2 weeks (median 16) from an average of 1.9 +/- 0.5 weeks (median 2) compared to diagnostic 0.5% bupivacaine block. Following block resolution, the average pain scores and PDI returned to similar levels as before BoNT-A block. In conclusion, BoNT-A occipital nerve blocks provided a much longer duration of analgesia than diagnostic local anesthetics. The functional capacity improvement measured by PDI was profound enough in the majority of the patients to allow patients to resume their regular daily activities for a period of time.
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PMID:Botulinum toxin occipital nerve block for the treatment of severe occipital neuralgia: a case series. 1798 66

The protein botulinum neurotoxin A (BoNT/A) is one of seven distinct neurotoxins produced by Clostridium botulinum. BoNT/A blocks cholinergic synapses with an extremely high specificity and potency. Appropriately purified and diluted, BoNT/A serves as a reliable and well tolerated drug that is applied by local injection.The efficacy of BoNT/A is evident in the symptomatic therapy of disorders in which muscular hyperactivity plays a prominent role, such as focal dystonias and hemifacial spasm; in these disorders, BoNT/A is considered first-line therapy. BoNT/A is also beneficial in the treatment of both adults and children with spasticity of various causes. The pain that frequently accompanies these conditions is effectively reduced by BoNT/A. A genuine analgesic effect for BoNT/A unrelated to skeletal muscle spasmolysis has been suggested on the basis of in vitro and in vivo (animal) data. However, studies in humans designed to detect such an effect were negative, as were controlled studies of BoNT/A in patients with primary headache disorders.BoNT/A also acts on cholinergic synapses of the autonomic nervous system, and injection of BoNT/A into salivary glands significantly decreases the production of saliva. This may be beneficial for patients with Parkinson's disease, in whom the excessive production of saliva may be problematic.Overall, BoNT/A has been confirmed as an efficacious, predictable and well tolerated drug in an ever-increasing number of neurological disorders.
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PMID:Use of botulinum toxin A in adult neurological disorders: efficacy, tolerability and safety. 1869 73

Today, botulinumtoxin A (BoNT-A) is applied for a broad spectrum of therapeutic uses. Experimental and clinical studies indicate that it also affects certain kinds of pain. One example of its prophylactic use is for chronic daily headache (CDH), defined as 15 days per month with headache. As shown by subgroup analyses in a phase II study, patients treated with BoNT-A and no additional treatment had significantly more pain-free days than those treated with placebo. They also required less frequent administration of headache medicines. Important was also the recognition that repeat treatments with BoNT-A at dosages of up to 260 U were safe and showed no difficult side effects. Phase III clinical studies are already being conducted.
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PMID:[First results of clinical studies on botulinum toxin A in migraine and headache]. 1892 67

Recent scientific data support an effect of botulinum neurotoxin (BoNT) on pain and headache. BoNT was shown to affect the release of neurotransmitters that are important in pain transmission and in migraine pathogenesis. Data from both animal and clinical studies suggest that the toxin may have an analgesic effect that is independent from its effect on muscle tone. The high tolerability and long duration of action of the drug make it appealing as a potential prophylactic treatment for headache patients. Results of controlled trials on the efficacy of BoNT in the treatment of episodic migraine (EM) are mostly negative, although some subgroups of patients (eg, those with high attack frequency) may respond to the drug. Studies of patients with chronic daily headache have been inconclusive, although (as with the EM studies) specific subgroups of patients appear to benefit from the drug. BoNT is probably ineffective for the treatment of chronic tension-type headache. There are anecdotal reports on a positive effect of BoNT in patients with other types of headache (eg, nummular headache). Factors that may affect the response of patients to BoNT include headache characteristics, disease duration, the use of concurrent preventive medications, and the presence or absence of medication overuse. The authors' clinical experience shows that some headache patients benefit significantly from BoNT treatment. The challenge for future studies is to identify those patients who will best respond to the drug.
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PMID:Is botulinum toxin useful in treating headache? Yes. 1909 33

The discrepancy between the widespread use of botulinum neurotoxin (BoNT) in managing headache and the supporting clinical evidence is unprecedented. No substance seems to have inspired more physicians and patients to undertake spirited treatment attempts. Tremendous treatment success in small, uncontrolled clinical trials has been repeatedly reported, but no substance that has been studied to an equal extent has so utterly failed to provide proof of effect in controlled clinical trials. Nevertheless, even though most randomized, controlled clinical trials have not met their defined primary outcome criterion, BoNT is still considered a promising treatment alternative for primary headache disorders. Experimental approaches to the pathophysiologic impact of BoNT on the perception of pain have been equally unsuccessful. Although most studies have been unable to find a direct antinociceptive effect in humans, some researchers continue to seek specific injection sites or injection techniques that may promise more successful results. Others look for a positive effect by narrowing the indications for BoNT to more homogenous symptoms or special patient subgroups. The results of randomized, controlled studies involving a total of 3552 patients indicate that BoNT injection is probably ineffective for patients with migraine and chronic tension-type headache regardless of injection site, dosage, or injection regimen, and there is insufficient evidence to draw a conclusion about its effectiveness for the treatment of chronic daily headache or subforms. The lack of direct experimental or clinical trial evidence that BoNT has a direct antinociceptive effect in humans must be addressed before more trials are conducted, involving even more patients. Additional pathophysiologically oriented research is also needed to unravel the mechanisms of action of BoNT in human pain perception or, alternatively, to bring it all down to the placebo effect.
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PMID:Is botulinum toxin useful in treating headache? No. 1909 32

Comparator studies that assess treatment effects in a clinical setting have improved the understanding of the efficacy and tolerability of prophylactic treatments for chronic migraine (CM). It is premature to recommend device-based treatments, such as occipital nerve stimulation, vagal nerve stimulation, and patent foramen ovale closure for CM, because clinical trials are in the preliminary stages. Physical therapy techniques, like applying heat or cold packs, ultrasonography, and electrical stimulation, have been shown to lessen pain. Nonpharmacologic treatments, including cognitive behavioral therapy, stress management, and biofeedback, have been investigated and proved effective in some areas of pain management, including migraine. However, pharmacologic interventions may be necessary for effective, long-term prophylaxis. Several medications under investigation, including topiramate, gabapentin, tizanidine, and amitriptyline, have proved efficacious in reducing the number of migraine episodes and the pain associated with migraine, although adverse events may prevent continued use of some agents. Evidence supports the use of botulinum toxin type A (BoNT-A) for CM, with or without medication overuse, to achieve a significant reduction in headache episodes. Efficacy of BoNT-A for CM is comparable with or better than that of valproate and topiramate, with better tolerability. Predictors of response to BoNT-A for CM appear to include predominantly unilateral location of the headache and the presence of cutaneous or muscle allodynia. BoNT-A has been demonstrated to be safe and well tolerated, with rare discontinuations due to adverse events. Recent clinical trials indicate that rational combination therapy may have a place in treating refractory CM. Well-controlled multicenter trials are awaited.
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PMID:Dynamic optimization of chronic migraine treatment: current and future options. 1918 63


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