Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 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

The trigeminovascular system is involved in migraine. Efficacy of Botulinum Toxin type A (BoNT-A) in migraine has been investigated in clinical studies but the mechanism of action remains unexplored. It is hypothesized that BoNT-A inhibits peripheral sensitization of nociceptive fibers and indirectly reduces central sensitization. We examined the effect of intramuscular injection of BoNT-A on an experimental human model of trigeminal sensitization induced by intradermal capsaicin injection to the forehead. BoNT-A (BOTOX) or saline was injected intramuscularly in precranial, neck and shoulder muscles to 32 healthy male volunteers in a double blind-randomized manner. Intradermally capsaicin-induced pain, flare and secondary hyperalgesia were obtained before and 1, 4 and 8 weeks after the above treatments. A significant suppressive effect of BoNT-A on pain, flare and hyperalgesia area was observed. The pain intensity area was significantly smaller in BoNT-A group (9.16+/-0.83 cm x s) compared to saline group (15.41+/-0.83cm x s) (P=0.011). The flare area was also reduced significantly in BoNT-A group (29.81+/-0.69 cm2) compared to saline group (39.71+/-0.69 cm2) (P<0.001). Similarly, the mean area of secondary hyperalgesia was significantly smaller in BoNT-A group (4.25+/-0.91 cm2) compared to saline group (7.03+/-0.91 cm2) (P=0.040). Post hoc analysis showed significant differences across the trials with a remarkable suppression effect of BoNT-A on capsaicin-induced sensory and vasomotor reactions as early as week1 (P<0.001). BoNT-A presented suppressive effects on the trigeminal/cervical nociceptive system activated by intradermal injection of capsaicin to the forehead. The effects are suggested to be caused by a local peripheral effect of BoNT-A on cutaneous nociceptors.
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PMID:The effects of Botulinum Toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization. 1667 61

Since its development for the use of blepharospasm and strabismus more than 2.5 decades ago, botulinum neurotoxin (BoNT) has become a versatile drug in various fields of medicine. It is the standard of care in different disorders such as cervical dystonia, hemifacial spasm, focal spasticity, hyperhidrosis, ophthalmological and otolaryngeal disorders. It has also found widespread use in cosmetic applications. Many other indications are currently under investigation, including gastroenterologic and urologic indications, analgesic management and migraine. This paper is an extensive review of the spectrum of BoNT clinical applications.
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PMID:Botulinum toxin: clinical use. 1687 Apr 87

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.
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PMID:Long-term benefits of botulinum toxin type A (BOTOX) in chronic daily headache: a five-year long experience. 1714 65

This article reviews the appropriate use, cautions, and contraindication for botulinum neurotoxin (BoNT) and reviews the peer-reviewed literature that describes its efficacy for treatment of various chronic orofacial pain disorders. The literature has long suggested that BoNT is of value for orofacial hyperactivity and more recently for some orofacial pain disorders; however, the results are not as promising for orofacial pain. The available data from randomized, double-blind, placebo-controlled trials (RBCTs) do not support the use of BoNT as a substantially better therapy than what is being used already. The one exception is that BoNT has reasonable RBCT data to support its use as a migraine prophylaxis therapy. The major caveat is that the use of BoNT in chronic orofacial pain is "off-label".
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PMID:A critical review of the use of botulinum toxin in orofacial pain disorders. 1718 69

Preventive measures are necessary against contraction of botulism through food intake or due to other factors because the botulinum neurotoxin (BoNT) is one of the strongest toxins. Despite this, given its therapeutic utility in the controll of neuromuscular transmission, BoNT has been utilized to treat diseases related to muscular hyperactivity, such as dystonia and spasticity. Furthermore, it has been recognized that BoNT is also useful in controlling the neurotransmitter release of sensory and autonomic nerve terminals as well. This paper reviews the recent progress in the therapeutic use of BoNT in pain management, for example, in condition such as migraine, myofascial pain syndrome, pelvic pain, and interstitial cystitis.
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PMID:[Use of botulinum toxin for pain therapy]. 1851 72

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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