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)

Botulinum neurotoxin type A is one of the most toxic substances known to man (LD(50) for mouse 0.1 ng/kg). It is also an effective therapeutic drug against involuntary muscle disorders and for pain management. BoNT/A is a Zn(2+) endopeptidase which selectively cleaves SNAP-25 (synaptosomal-associated protein of 25 kDa), a critical component of the exocytotic machinery. Based on nucleotide sequence, BoNT/A is a 145 kDa protein, which appears as a 145 kDa protein band on sodium dodecyl sulfate--polyacrylamide gel electrophoresis. We have examined the structure of BoNT/A in aqueous solution, and found the structure in aqueous solution differs dramatically from that resolved by X-ray crystallography, both at secondary and at quaternary levels. In terms of secondary structure, BoNT/A in aqueous solution has about 47% beta-sheet structure as revealed by infrared spectroscopy, while X-ray crystallography revealed only 17% beta-sheet structure. In terms of quaternary structure, the estimated molecular mass of the native BoNT/A in aqueous solution ranged between 230 and 314 kDa, based on results from different chemical and biophysical techniques (native gel electrophoresis, chemical cross-linking, size exclusion chromatography, and fluorescence anisotropy). These results indicate that BoNT/A exists as a dimer in aqueous solution, which contrasts with the reported monomeric structure of BoNT/A based on X-ray crystallography. The dimeric form of BoNT/A can self-dissociate into the monomeric form at a concentration lower than 50 nM. This concentration-dependent structural change has a significant impact on the endopeptidase activity of BoNT/A: the catalytic efficiency of the monomeric BoNT/A is about 4-fold higher than that of its dimeric form. This difference implies a sterically restricted catalytic site of BoNT/A in the dimeric form of BoNT/A.
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PMID:A correlation between differential structural features and the degree of endopeptidase activity of type A botulinum neurotoxin in aqueous solution. 1129 37

Cervical dystonia (CD) causes involuntary muscle spasms and is often associated with pain. Recently, botulinum toxin type B (BTX-B) (Myobloc, Elan South San Francisco, CA, USA) was approved for general use in the treatment of CD in the USA. In two large pivotal trials, BTX-B was found to be safe and effective in decreasing the movements, pain and disability associated with CD. Benefits were noted both in patients who no longer respond and in those who continue to respond to botulinum toxin type A (BTX-A). BTX-B offers an additional therapeutic option for patients with CD.
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PMID:Botulinum toxin type B: a new injectable treatment for cervical dystonia. 1177 15

Aside from temporary chemodenervation of skeletal muscle and potential anti-inflammatory effects, a genuine peripheral antinociceptive effect of Botulinum Neurotoxin Type A (BoNT/A) has been suspected. To evaluate the effect of BoNT/A on cutaneous nociception in humans, 50 healthy volunteers received subcutaneous injections of 100 mouse units (MU) BoNT/A (Dysport) and placebo. Both forearms of each subject were treated in a double-blind fashion, one with verum, one with placebo. Heat and cold pain thresholds within the treated skin areas were measured with quantitative sensory testing (QST) and pain thresholds were evaluated with local electrical stimulation (ES). The tests were done before treatment, and after 4 and 8 weeks. No major side effects were noted. All participants completed the study. Heat and cold pain thresholds increased from baseline to week 4 by 1.4 degrees C for verum and by 1.1 degrees C for placebo. From baseline to week 8, the thresholds increased by 2.7 degrees C for verum and by 1.2 degrees C for placebo. Electrically induced pain thresholds shifted from baseline to week 4 by -0.07 mA for verum and by 0.01 mA for placebo. From baseline to week 8, the thresholds increased by 0.10 mA for verum and by 0.11 mA for placebo. None of these differences was statistically significant. The study shows that there is no direct peripheral antinociceptive effect of BoNT/A in humans. The efficacy of BoNT/A in various pain syndromes must be explained by other pathways such as chemodenervation or anti-inflammatory effects.
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PMID:Botulinum toxin A and the cutaneous nociception in humans: a prospective, double-blind, placebo-controlled, randomized study. 1240 85

Botulinum toxin has dramatically improved the treatment of a variety of neurologic disorders. Two botulinum toxin preparations are commercially available in the United States: type A (Botox) and type B (Myobloc). Current indications approved by the United States Food and Drug Administration include cervical dystonia, strabismus, blepharospasm, hemifacial spasm, and glabellar wrinkles for Botox, and cervical dystonia for Myobloc. Botulinum toxin inhibits release of acetylcholine from the neuromuscular junction, resulting in a localized paralysis when minute doses are injected. This mechanism enables botulinum toxin to alleviate symptoms of focal dystonias (which are characterized by excessive muscle contraction), and it may also, along with other theoretical mechanisms, be responsible for pain relief. Studies conducted in patients with cervical dystonia have shown that botulinum toxin effectively reduces pain associated with this disorder, suggesting that this agent may be effective in alleviating other painful syndromes.
Clin J Pain
PMID:Review of the FDA-approved uses of botulinum toxins, including data suggesting efficacy in pain reduction. 1256 61

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.
Clin J Pain
PMID:Use of botulinum toxin in chronic whiplash-associated disorder. 1256 64

This article reviews the current status of dermatological uses for botulinum toxin type A (Botox), recently approved in the United States for treatment of glabellar wrinkles, and type B (Myobloc), approved for cervical dystonia. The respective formulations of Botox and Myobloc are described, and injection techniques and special considerations for administration in the treatment of dermatologic conditions are also discussed. The use of botulinum toxin injections for cosmetic treatment of movement-related facial lines and platysmal bands in the neck is reviewed, including injection procedures, efficacy, and potential complications. Recent developments in the use of botulinum toxins for the treatment of palmar and axillary hyperhidrosis are also described, comparing type A and type B results. Although direct comparisons between botulinum toxins for dermatologic applications are complicated by the lack of functional equivalence of the standard potency assays, appropriate dosing strategies for obtaining satisfactory clinical results using type B are being established, which will add to the experience already gained with type A. The diffusion characteristics of type B appear to show different and potentially advantageous clinical profiles in the treatment of crows' feet and hyperhidrosis compared with type A.
Clin J Pain
PMID:Review of the use of botulinum toxin for hyperhidrosis and cosmetic purposes. 1256 68

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 neurotoxin (BoNT) is a potent biological substance used to treat neuromuscular and pain disorders. Both BoNT type A and BoNT type E display high-affinity uptake into motor neurons and inhibit exocytosis through cleavage of the synaptosome-associated protein of 25 kDa (SNAP25). The therapeutic effects of BoNT/A last from 3 to 12 months, whereas the effects of BoNT/E last less than 4 weeks. Using confocal microscopy and site-specific mutagenesis, we have determined that the protease domain of BoNT/A light chain (BoNT/A-LC) localizes in a punctate manner to the plasma membrane, colocalizing with the cleaved product, SNAP25(197). In contrast, the short-duration BoNT/E serotype is cytoplasmic. Mutations in the BoNT/A-LC have revealed sequences at the N terminus necessary for plasma membrane localization, and an active dileucine motif in the C terminus that is likely involved in trafficking and interaction with adaptor proteins. These data support sequence-specific signals as determinants of intracellular localization and as a basis for the different durations of action in these two BoNT serotypes.
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PMID:Plasma membrane localization signals in the light chain of botulinum neurotoxin. 1498 88

Myofascial pain syndrome is defined as subacute or chronic pain with sensory, motor and autonomic symptoms referred from active trigger points with associated painful dysfunctions. Authors present the usefulness of botulinum toxin A or B (BoNT/A or BoNT/B) injected into target muscles since the toxin is capable of controlling not only the muscular spasm but mostly the pain by alternative mechanisms of action, which are discussed. Posology of BoNT, technical aspects and results are presented. BoNT represents an interesting and useful tool for an adequate management of patients with myofascial pain.
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PMID:Botulinum toxin (BoNT) and back pain. 1499 38


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