Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Whiplash-associated disorders (WADs) occur as a result of trauma and are often due to motor vehicle accidents and sports injuries. Cervical injury is attributed to rapid extension followed by neck flexion. The exact pathophysiology of WAD is uncertain but probably involves some degree of aberrant muscle spasms and may produce a wide range of symptoms. Initial treatment of pain associated with whiplash usually includes oral medications, such as muscle relaxants and nonsteroidal anti-inflammatory drugs. However, these agents are limited by potential systemic adverse effects. Some patients with chronic WAD may benefit from radiofrequency neurotomy. A new approach to treatment is the use of botulinum toxin, which acts to reduce muscle spasms. Type A toxin (Botox) has been studied in small trials of patients with WAD and has generally been found to relieve pain and improve range of motion. In addition, recent preliminary data from a small trial showed that type B toxin (Myobloc) produced almost immediate pain relief for most patients with post-whiplash headache. Although botulinum toxin has not been evaluated in large long-term trials, these initial data are promising and suggest a role for this agent in the treatment of WAD. Additional study is needed to identify the subset of patients with WAD who are most likely to respond to treatment with botulinum toxin.
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PMID:Use of botulinum toxin in chronic whiplash-associated disorder. 1256 64

Botulinum toxin A (BoNT/A) has been used therapeutically to treat muscular hypercontractions and sudomotor hyperactivity. There is increasing evidence that BoNT/A might also have analgesic properties, in particular in headache. In the present investigation we tested the often cited hypothesis that BoNT/A-induced analgesia can be attributed to inhibition of neuropeptide release from nociceptive nerve fibers. In 15 healthy volunteers BoNT/A (5, 10, 20 mouse units BOTOX) or saline (contralateral side) was injected intracutaneously on the volar forearm. On day zero, the day of injection, no further tests were performed. We repeatedly elicited pain, mechanical hyperalgesia and neurogenic flare by transcutaneous electrical stimulation simultaneously on the BoNT/A and saline treated side on day 1, 2, 3, 7 and 14 after injection. Before each session, sweating and local anhidrosis was assessed by iodine starch staining.BoNT/A suppressed sweating as early as from the second day after injection (p < 0.001). The size of electrically induced flare was smaller on the BoNT/A treated arm (BoNT/A side: 21.46 cm(2) +/- 3.58, saline side 24.80 +/- 3.46, p < 0.005) and BoNT/A reduced electrically-induced pain by about 10 % (p < 0.001). However, hyperalgesia to pin-prick and allodynia after electrical stimulation were unchanged. In conclusion our results indicate that peripheral neuropeptide release is attenuated by BoNT/A. In contrast, the analgesic effect of BoNT/A was very limited. Therefore we assume that other than neuropeptide mechanisms must be important for BoNT/A induced pain relief in clinical pain syndromes.
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PMID:Botulinum Toxin A reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin. 1257 49

The use of botulinum toxin in the management of various neurologic and non-neurologic disorders has grown considerably over the past decade. At the same time, new information regarding the mechanism of action of these toxins has evolved allowing for a greater understanding of the versatility of these agents. Although two types of botulinum toxin (type A Botox and type B Myobloc ) are commercially available in the US, most studies of the use of these toxins for the management of chronic pain and headache have been completed with type A. Data from open-label and retrospective studies as well as clinical practice suggest as strongly as possible that there is a role for these agents, especially Botox, in the management of several chronic headache disorders, including chronic migraine, chronic tension-type, cervicogenic, and cluster headache. Emerging data regarding the use of these agents for so-called "analgesic-rebound" headache also appear impressive; however, as of yet, no multicenter, randomized, controlled studies for any headache type have been published that confirm the results seen in noncontrolled studies. Nevertheless, the benefit that some patients experience from this agent is impressive, and this drug appears for many to modify the disorder in a very positive manner. In a similar fashion, data for other pain states are often restricted to open-label and case study approaches; however, clinical experience and some of the available studies (even small controlled studies) suggest a role for the toxins in the management of various chronic pain states, such as myofascial pain, low back pain, and neuropathic pain. One of the greatest challenges ahead for all interested in this area is confirming the benefit seen clinically through appropriately designed multicenter, randomized, controlled studies.
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PMID:The Use of Botulinum Toxins for Chronic Pain and Headaches. 1451 25

Botulinum toxin A (BoNT/A), a neurotoxin, is effective for treating a variety of disorders of involuntary muscle contraction, including cervical dystonia, blepharospasm and hemifacial spasm. It inhibits neurouscular 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 3-6 months post injection. Recently, clinical findings suggest that BoNT/A may inhibit pain associated with migraine and other headache types. The mechanism by which this toxin inhibits pain is under investigation, recent findings suggest that it inhibits the release of neurotransmitters from nociceptive nerve terminals and in this way may exert an analgesic effect. A number of retrospective open-label chart reviews and three placebo-controlled double-blind trials have demonstrated that localized injections of BTX-A significantly reduce migraine frequency, severity, and migraine-associated disability. The majority of patients in these studies experienced no BoNT/A mediated side effects; however, a small percentage of patients did report transient minor side effects including blepharoptosis, dipolpia, and injection-site weakness. Currently there are several large-scale randomized, placebo-controlled clinical trials in progress evaluating the efficacy, optimal dosing and side effect profile of this toxin as a novel treatment for migraine and other headache types. These studies may provide further evidence that BoNT/A is an effective option for the preventive treatment of migraine.
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PMID:Botulinum neurotoxin for the treatment of migraine and other primary headache disorders. 1515 49

Most of the initial reports on botulinum toxin in tension-type headache (TTH) and in migraine were positive. Unfortunately, these results were not reproduced in well-designed, randomized controlled trials. So far, doses from 20 U (Botox) to 500 U (Dysport) have been studied in patients with chronic TTH, and doses from 16 to 200 U (Botox) in patients with migraine. Overall, there is no evidence for a beneficial effect of botulinum toxin, although trends favoring botulinum toxin were reported. Experience with botulinum toxin type B (Myobloc/NeuroBloc) is limited and similar to the experience with the type A. Thus, a widespread use of botulinum toxin therapy in headache can currently not be recommended.
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PMID:Botulinum toxin therapy of migraine and tension-type headache: comparing different botulinum toxin preparations. 1641 98

Botulinum neurotoxin A (BoNT/A) has been used therapeutically to treat muscular hypercontractions and sudomotor hyperactivity and it has been reported that BoNT/A might have analgesic properties in headache. PEP-1 peptide is a known carrier peptide that delivers full-length native proteins in vitro and in vivo. In this study, a BoNT/A gene were fused with PEP-1 peptide in a bacterial expression vector to produce a genetic in-frame PEP-1-BoNT/A fusion protein. The expressed and purified PEP-1-BoNT/A fusion proteins were efficiently transduced into cells in a time- and dose-dependent manner when added exogenously in a culture medium. In addition, immunohistochemical analysis revealed that PEP-1-BoNT/A fusion protein efficiently penetrated into the epidermis as well as the dermis of the subcutaneous layer, when sprayed on mice skin. These results suggest that PEP-1-BoNT/A fusion protein provide an efficient strategy for therapeutic delivery in various human diseases related to this protein.
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PMID:Expression, purification and transduction of PEP-1-botulinum neurotoxin type A (PEP-1-BoNT/A) into skin. 1700 86

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

Trigeminal neuralgia (TN) patients may develop side effects from centrally acting drugs, have contraindications for neurosurgical procedures, or experience relapse during conventional therapies. OnabotulinumtoxinA (BoNT/A) has been reported to be effective for TN, although this finding has been challenged. An overview of the available evidence based on a narrative/qualitative analysis of the literature is presented. About 90% of patients who receive BoNT/A show an improvement, a higher figure than that reported for the placebo effect of BoNT/A for other headaches. Tolerability of BoNT/A is good, and its few side-effects are transient. The articles reviewed were mainly case reports, case series and open-label trials; however, randomized controlled trials have endorsed the efficacy of BoNT/A for TN. This evidence, together with a better understanding of the analgesic mechanisms of BoNT/A and its proven efficacy in treating other pain syndromes, supports the use of this toxin as a therapeutic option for TN.
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PMID:OnabotulinumtoxinA for trigeminal neuralgia: a review of the available data. 2629 95

Botulinum neurotoxin A (BoNT/A) is a toxin produced by the naturally-occurring Clostridium botulinum that causes botulism. The potential of BoNT/A as a useful medical intervention was discovered by scientists developing a vaccine to protect against botulism. They found that, when injected into a muscle, BoNT/A causes a flaccid paralysis. Following this discovery, BoNT/A has been used for many years in the treatment of conditions of pathological muscle hyperactivity, like dystonias and spasticities. In parallel, the toxin has become a "glamour" drug due to its power to ward off facial wrinkles, particularly frontal, due to the activity of the mimic muscles. After the discovery that the drug also appeared to have a preventive effect on headache, scientists spent many efforts to study the potentially-therapeutic action of BoNT/A against pain. BoNT/A is effective at reducing pain in a number of disease states, including cervical dystonia, neuropathic pain, lower back pain, spasticity, myofascial pain and bladder pain. In 2010, regulatory approval for the treatment of chronic migraine with BoNT/A was given, notwithstanding the fact that the mechanism of action is still not completely elucidated. In the present review, we summarize experimental evidence that may help to clarify the mechanisms of action of BoNT/A in relation to the alleviation of headache pain, with particular emphasis on preclinical studies, both in animals and humans. Moreover, we summarize the latest clinical trials that show evidence on headache conditions that may obtain benefits from therapy with BoNT/A.
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PMID:Botulinum Toxin Type a as a Therapeutic Agent against Headache and Related Disorders. 2640 77

Botulinum toxin serotype A (BoNT/A) was originally used in neurology for the treatment of dystonia and blepharospasms, but is now clinically used worldwide for the treatment of chronic migraine. Still, the possible mode of action of BoNT/A in migraine is not fully known. However, the mode of action of BoNT/A has been investigated in experimental pain as well as migraine models, which may elucidate the underlying mechanisms in migraine. The aim of this study was to review studies on the possible mode of action of BoNT/A in relation to chronic migraine treatment. Observations suggest that the mode of action of BoNT/A may not be limited to the injection site, but also includes anatomically connected sites due to axonal transport. The mechanisms behind the effect of BoNT/A in chronic migraine may also include modulation of neurotransmitter release, changes in surface expression of receptors and cytokines as well as enhancement of opioidergic transmission. Clinical and experimental studies with botulinum toxin in the last decade have advanced our understanding of headache and other pain states. More research into botulinum toxin as treatment for headache is warranted as it can be an attractive alternative for patients who do not respond positively to other drugs.
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PMID:Botulinum toxin: A review of the mode of action in migraine. 2988 65


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