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

Primary stabbing headache is an ultra-short headache, associated with primary headaches, more prevalent in women and with a poor response to therapy. The effect of botulinum neurotoxin type-A (BoNTA) on primary stabbing headache was investigated in 24 patients. Three patients showed complete remission. Nineteen patients showed a decrease in their primary stabbing headaches that started in the second week, and that was sustained during approximately 63 days. In two patients BoNTA showed no therapeutic effect. The BoNTA seems to be an excellent therapeutic option for primary stabbing headache.
 ...
PMID:Botulinum neurotoxin type-A for primary stabbing headache: an open study. 2046 87

OnabotulinumtoxinA has recently been approved by regulatory agencies in the UK and United States for treatment of chronic migraine based on data generated from the PREEMPT studies. As such, onabotulinumtoxinA is the only prophylactic therapy specifically approved for chronic migraine. Most headache clinicians would agree that acute episodic migraine and chronic migraine differ in their pathophysiology, etiology, diagnosis, and response to pharmacological as well as nonpharmacological therapies. Of the 7 botulinum neurotoxin serotypes, botulinum neurotoxin type A (onabotulinumtoxinA) has been the most thoroughly investigated in preclinical and clinical studies. Based on preclinical studies, onabotulinumtoxinA is known to inhibit the release of excitatory neurotransmitters from both motor and sensory neurons by preventing vesicle fusion to the cell membrane. In addition to the well-documented myorelaxant effects of this neurotoxin, onabotulinumtoxinA can exert a direct analgesic effect that likely involves inhibition of primary and secondary nociceptive neurons. The inhibitory effects of onabotulinumtoxinA are also likely to involve suppressing the activity of myogenic trigger points and decreasing the persistent nociceptive barrage that promotes and maintains central sensitization. This article describes possible mechanisms to explain how onabotulinumtoxinA functions as a therapy for chronic migraine and considers why treatment with the neurotoxin is not effective in some chronic migraineurs.
Headache
PMID:Insights into the mechanism of onabotulinumtoxinA in chronic migraine. 2208 29

Botulinum neurotoxin type-A (BoNT-A) is clinically used for patients with pain disorders and dystonia. The precise mechanism whereby BoNT-A controls pain remains elusive. Here, we studied how BoNT-A affects the expression of the transient receptor potential vanilloid subfamily member 1 (TRPV1), a cation channel critically implicated in nociception, in the trigeminal system. Histological studies revealed that subcutaneous BoNT-A injection (0.25, 0.5, or 5 ng/kg) into the face targeted the ophthalmic division of trigeminal ganglion (TG) neurons and decreased TRPV1-immunoreactive neurons in the TG and TRPV1-immunoreactive fibers in rat trigeminal terminals. Of note, TG neurons that received projections from the dura mater, a principal site of headache generation, had reduced TRPV1 expression. BoNT-A-induced cleavage of SNAP25 (synaptosomal-associated protein of 25-kDa) in the TG became obvious 2 days after BoNT-A administration and persisted for at least 14 days. Quantitative real-time RT-PCR (reverse transcription-polymerase chain reaction) data indicated that the TRPV1-decreasing effects of BoNT-A were not mediated by transcriptional downregulation. By employing a surface protein biotin-labeling assay, we demonstrated that BoNT-A inhibited TRPV1 trafficking to the plasma membrane in primary TG neurons. Moreover, Y200F-mutated TRPV1, which is incapable of trafficking to the plasma membrane, was expressed in PC12 cells by transfection, and pharmacological studies revealed that TRPV1 in the cytoplasm was more predisposed to proteasome-mediated proteolysis than plasma membrane-located TRPV1. We conclude that the mechanism by which BoNT-A reduces TRPV1 expression involves the inhibition of TRPV1 plasma membrane trafficking and proteasome-mediated degradation in the cytoplasm. This paradigm seems to explain how BoNT-A alleviates TRPV1-mediated pain. Our data reveal a likely molecular mechanism whereby BoNT-A treatment reduces TRPV1 expression in the trigeminal system and provide important clues to novel therapeutic measures for ameliorating craniofacial pain.
 ...
PMID:Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A. 2282 Jan 41

Although migraine is a common, paroxysmal, highly disabling disorder, the primary cause and the pathomechanism of migraine attacks are enigmatic. Experimental results suggest that activation of the trigeminovascular system is crucial in its pathogenesis. This activation leads to the release of vasoactive neuropeptides (calcitonin gene-related peptide - CGRP, and substance P - SP) and to neurogenic inflammation, and peripheral and central sensitisation are expressed. Botulinum neurotoxin-A (BoNT-A), a potent toxin produced by Clostridium botulinum, affects the nervous system through specific cleavage of the soluble NSF-attachment protein receptor complex (SNARE), like synaptosomal-associated protein of 25 kDa (SNAP-25). The result of this multistage process is blockade of the presynaptic release of pain neurotransmitters such as CGRP, SP and glutamate. A pooled analysis of the data from two programmes of Phase 3 Research Evaluating Migraine Prophylaxis Therapy (PREEMPT 1 and 2) with BoNT-A in chronic migraine demonstrated significant benefit of BoNT-A over placebo with regard to the numbers of headache days and migraine episodes. BoNT-A diminished the frequency of acute headache pain medication intake, and resulted in reductions in headache impact and improvements in scores on the Migraine-Specific Quality of Life Questionnaire. The treatments with BoNT-A proved safe and were well tolerated.
 ...
PMID:[Botulinum neurotoxin--a therapy in migraine]. 2313 25

Botulinum toxin, a potent muscle relaxant, has been found to have analgesic effects in patients with various pain syndromes. Both in vitro and in vivo studies showed the ability of the toxin to block the release of pain neurotransmitters, such as substance P, glutamate, and calcitonin gene-related peptide. The effect of the toxin, and specifically of one of its serotypes, botulinum neurotoxin type A, on headaches, has been extensively studied. This serotype is available in the United States in 3 forms, including as onabotulinumtoxinA. Data from clinical trials confirmed the efficacy, safety, and tolerability of onabotulinumtoxinA in the prophylactic treatment of chronic migraine, the most severe and debilitating type of migraine, in adults. The drug was approved by the Food and Drug Administration for this indication in 2010. The drug was not found to be effective for episodic migraine or tension-type headache. Noncontrolled studies suggest the efficacy of the toxin for headache associated with craniocervical dystonia. Proper injection technique and appropriate patient selection are essential for achieving positive results after treatment with onabotulinumtoxinA. The recommended injection paradigm combines a fixed site/fixed dose and follow the pain approaches, with the toxin injected to multiple sites of the head and neck, at a total dose of 155U-195U. The treatment is given at intervals of 12 weeks on average. The efficacy of onabotulinumtoxinA for some headaches, its long duration of action, and its favorable adverse effect profile make it a viable treatment option for the appropriate headache patients. The drug may be particularly suitable for patients who cannot tolerate, or are not compliant with, the daily intake of oral headache preventive drugs.
Headache 2013 Sep
PMID:OnabotulinumtoxinA for the treatment of headache. 2402 3

Botulinum neurotoxin A is a category A bioterrorism agent. Current antitoxin therapies are scarce and produce adverse reactions. XOMA 3AB consists of 3 IgG1 monoclonal antibodies (MAbs), each with a distinct human or humanized variable region, which bind to distinct epitopes on botulinum neurotoxin serotype A. This first-in-human study evaluated the safety and pharmacokinetics (PK) of escalating doses of XOMA 3AB administered intravenously (i.v.) to healthy adults. In this double-blind placebo-controlled dose escalation study, 3 cohorts of 8 healthy subjects received a single intravenous dose of XOMA 3AB or placebo at a 3:1 ratio. Follow-up examinations included physical examinations, hematology and chemistry blood tests, electrocardiograms, and pharmacokinetics. Pharmacokinetic parameters were estimated using noncompartmental methods. There were no infusion discontinuations or hypersensitivity reactions. Two or more subjects experienced headache, hyperglycemia, or anemia; none was dose related. All adverse events (AEs) were mild to moderate except for an episode of exercise-induced elevation of a subject's creatine phosphokinase (CPK) level, unrelated to XOMA 3AB. Concentration-time plots demonstrated a peak in MAb concentrations 1 to 2 h after completion of the infusion, after which the levels declined in a biexponential decay pattern for all analytes. For each MAb, the maximum concentration of drug in serum (Cmax) and the area under the concentration-time curve from 0 to infinity (AUCinf) increased as the dose increased. Clearance of the humanized mouse MAb was more rapid than that of the two fully human MAbs, particularly at the lowest dose. None of the MAbs was immunogenic. At the doses administered, XOMA 3AB was well tolerated. These safety findings support further investigation of XOMA 3AB as a potential agent for botulism treatment and postexposure prophylaxis. (This study has been registered at ClinicalTrials.gov under registration no. NCT01357213.).
...
PMID:Safety and pharmacokinetics of XOMA 3AB, a novel mixture of three monoclonal antibodies against botulinum toxin A. 2491 60

Chronic migraine is a severely disabling headache evolving from episodic migraine as a result of different transforming factors and characterized by atypical pain modulation and peripheral and central sensitization. Discovered by serendipity, onabotulinum toxin A (BoNT-A) represents the only drug specifically approved for CM prophylaxis. According to the dominant opinion, BoNT-A acts peripherally, impairing the exocytosis of neuropeptide and neurotransmitter and the delivery of receptors and ion channels on the cell surface of peripheral trigeminal endings, thereby indirectly reducing central sensitization. However, it is not excluded that BoNT-A has also a central antinociceptive action, probably associated with an enhanced opioidergic and GABA-ergic transmission. This review discusses the rationale for use of BoNT-A in CM including its mechanisms of action and molecular targets and provides suggestions for a more tailored BoNT-A prophylaxis in patients with CM.
 ...
PMID:Rationale for use of onabotulinum toxin A (BOTOX) in chronic migraine. 2601 7

This paper reviews the current and most neurological (central nervous system, CNS) uses of the botulinum neurotoxin type A. The effect of these toxins at neuromuscular junction lends themselves to neurological diseases of muscle overactivity, particularly abnormalities of muscle control. There are seven serotypes of the toxin, each with a specific activity at the molecular level. Currently, serotypes A (in two preparations) and B are available for clinical purpose, and they have proved to be safe and effective for the treatment of dystonia, spasticity, headache, and other CNS disorders in which muscle hyperactivity gives rise to symptoms. Although initially thought to inhibit acetylcholine release only at the neuromuscular junction, botulinum toxins are now recognized to inhibit acetylcholine release at autonomic cholinergic nerve terminals, as well as peripheral release of neuro-transmitters involved in pain regulation. Its effects are transient and nondestructive, and largely limited to the area in which it is administered. These effects are also graded according to the dose, allowing individualized treatment of patients and disorders. It may also prove to be useful in the control of autonomic dysfunction and sialorrhea. In over 20 years of use in humans, botulinum toxin has accumulated a considerable safety record, and in many cases represents relief for thousands of patients unaided by other therapy.
...
PMID:Botulinum Neurotoxin Type A in Neurology: Update. 2648 28

OnabotulinumtoxinA (BoNT-A) has been reported as an effective prophylactic treatment for chronic migraine to reduce disease severity improving health-related quality of life. However, BoNT-A, due to its activity on either the injected or adjacent muscles of the upper face, may induce well-known side-effects, such as the eyebrow or eyelid ptosis. However, unusual muscular side effects, related to the neurotoxic mechanism, may also arise. We describe the clinical case of a 55-year-old male patient who has been treated for chronic migraine by the injection of BoNT-A, according to the PREEMPT protocol. Two weeks later, the patient developed two symmetrical bumps on the upper part of the forehead similar to the horns of a ram. We report, for the first time, this peculiar BoNT-A side effect and suggest that the injection of additional BoNT-A doses in the upper medial frontal fibers, for each side, can normalize the forehead shape over two weeks.
Headache 2016 Nov
PMID:The "Ram's Horns Sign": A Case Report of an Unusual Side Effect of OnabotulinumtoxinA in a Chronic Migraine Patient. 2739 16

Chronic migraine causes a serious labour loss and disability in the society and increases the risk of depression and anxiety by negatively affecting the quality of life. The purpose of this study was to investigate the effects of onabotulinumtoxinA (BoNT-A) treatment on efficacy before and after treatment in our cases with chronic migraine as well as on depression, anxiety and disability caused by migraine. According to the International Headache Classification (ICHD-III beta version), 60 adult patients who were diagnosed with chronic migraine were included in the study. A total of 155 IU BoNT-A treatment from 31 regions was administered in accordance with the protocol of PREEMPT study. Information about the characteristics of patients' headaches, background and family history, drugs they used was recorded. At the baseline and in the first and third month after the BoNT-A injection, VAS scores, the number of both headache days and attacks, the headache duration, the frequency of application to emergency services and the intake of both analgesics and triptans during attacks were evaluated. MIDAS, BDI and BAI were evaluated at the baseline and in the third month after the BoNT-A injection. BoNT-A injection provided a significant decrease in the number of days and severity of headaches, MIDAS disability scores and psychiatric complaints in cases with chronic migraine who did not respond to prophylactic treatments in the third month of the treatment.
 ...
PMID:Effects of onabotulinumtoxinA treatment on efficacy, depression, anxiety, and disability in Turkish patients with chronic migraine. 2741 78


<< Previous 1 2 3 Next >>