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Special Issue "Botulinum Neurotoxins and Nervous System: Future Challenges for Novel Indications"

A special issue of Toxins (ISSN 2072-6651). This special issue belongs to the section "Bacterial Toxins".

Deadline for manuscript submissions: closed (31 March 2018)

Special Issue Editor

Guest Editor
Dr. Siro Luvisetto

National Research Council (CNR) of Italy, Institute of Cell Biology and Neurobiology, Monterotondo Scalo, Roma 00015, Italy
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Special Issue Information

Dear Colleagues,

Botulinum toxins (BoNTs) are a true wonder of nature. Like Dr. Jekyll and Mr Hide, they have a double "personality" that makes them unique among toxins of bacterial origin. On the one hand, BoNTs are key components of several widely-used drugs, approved for a variety of clinical conditions, difficult to treat with other medicine. On the other hand, BoNTs are the causal agent of botulism and, with its highest toxicity among natural products, are one of the most dangerous bioterrorism agents. Both animal and clinical studies have extensively investigated the therapeutics effects for BoNTs, evidencing a variety of apparently different mechanisms which have in common the block of the cholinergic transmission at the neuromuscular junction. This discovery gave an extraordinary consensus to the clinical use of BoNTs in human pathologies characterized by excessive muscle contractions, i.e., the hypercholinergic dysfunctions going from torticollis, blepharospasms, dystonias, and so on. In recent years, a number of studies have provided evidence for the efficacy of BoNTs in alleviating human pain, including pain disorders associated with migraine. The list of human disorders in which treatments with BoNTs have produced, or are expected to produce, favorable results is long and continuously growing. This Special Issue “Botulinum Neurotoxins in Nervous System: Future Challenges for Novel Indications” is particularly devoted to collecting the most recent research on the effects of BoNTs in all cases where the expected therapeutic action is not attributable only to the its canonical mechanism, but also to the interaction of the toxins with other structures, including peripheral nerves, spinal cord, central neurons, non-neural cells, and so on. Both review and research articles are welcome, not only on animal studies, but also on clinical reports. The ambitious purpose of this Special Issue is to provide an up-to-date picture of the state-of-the-art on the possible development of novel BoNT applications for future therapeutic indications.

Dr. Siro Luvisetto
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Toxins is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1500 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Botulinum
  • Peripheral nervous system
  • Central nervous system
  • Sensory motor system
  • Nerve regeneration
  • Spinal cord
  • Glial cells
  • Animal models
  • Clinical studies

Published Papers (16 papers)

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Research

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Open AccessArticle Botulinum Neurotoxin Injection for the Treatment of Recurrent Temporomandibular Joint Dislocation with and without Neurogenic Muscular Hyperactivity
Received: 19 February 2018 / Revised: 20 April 2018 / Accepted: 20 April 2018 / Published: 25 April 2018
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Abstract
The aim of this study was to compare treatment outcomes following intramuscular injection of botulinum neurotoxin (BoNT) in patients with recurrent temporomandibular joint dislocation, with and without muscle hyperactivity due to neurological diseases. Thirty-two patients (19 women and 13 men, mean age: 62.3
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The aim of this study was to compare treatment outcomes following intramuscular injection of botulinum neurotoxin (BoNT) in patients with recurrent temporomandibular joint dislocation, with and without muscle hyperactivity due to neurological diseases. Thirty-two patients (19 women and 13 men, mean age: 62.3 years) with recurrent temporomandibular joint dislocation were divided into two groups: neurogenic (8 women and 12 men) and habitual (11 women and 1 man). The neurogenic group included patients having neurological disorders, such as Parkinson’s disease or oromandibular dystonia, that are accompanied by muscle hyperactivity. BoNT was administered via intraoral injection to the inferior head of the lateral pterygoid muscle. In total, BoNT injection was administered 102 times (mean 3.2 times/patient). The mean follow-up duration was 29.5 months. The neurogenic group was significantly (p < 0.001) younger (47.3 years) than the habitual group (84.8 years) and required significantly (p < 0.01) more injections (4.1 versus 1.7 times) to achieve a positive outcome. No significant immediate or delayed complications occurred. Thus, intramuscular injection of BoNT into the lateral pterygoid muscle is an effective and safe treatment for habitual temporomandibular joint dislocation. More injections are required in cases of neurogenic temporomandibular joint dislocation than in those of habitual dislocation without muscle hyperactivity. Full article
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Open AccessArticle Lumbar Sympathetic Block with Botulinum Toxin Type A and Type B for the Complex Regional Pain Syndrome
Received: 8 March 2018 / Revised: 9 April 2018 / Accepted: 16 April 2018 / Published: 19 April 2018
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Abstract
A lumbar sympathetic ganglion block (LSB) is a therapeutic method for complex regional pain syndrome (CRPS) affecting the lower limbs. Recently, LSB with botulinum toxin type A and B was introduced as a novel method to achieve longer duration of analgesia. In this
[...] Read more.
A lumbar sympathetic ganglion block (LSB) is a therapeutic method for complex regional pain syndrome (CRPS) affecting the lower limbs. Recently, LSB with botulinum toxin type A and B was introduced as a novel method to achieve longer duration of analgesia. In this study, we compared the botulinum toxin type A (BTA) with botulinum toxin type B (BTB) in performing LSB on patients with CRPS. LSB was performed with either BTA or BTB on patients with CRPS in their lower extremities. The length of time taken for patients to return to the pre-LSB pain score and the adverse effect of LSB with BTA/BTB were investigated. The median length of time taken for the patients to return to the pre-LSB pain score was 15 days for the BTA group and 69 days for the BTB group (P = 0.002). Scores on a visual analogue scale decreased in the patients of both groups, and no significant adverse effects were experienced. In conclusion, the administration of either BTA or BTB for LSB is a safe method to prolong the sympathetic blocking effect in patients with CRPS. BTB is more effective than BTA to prolong the sympathetic blocking effect in CRPS patients. Full article
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Open AccessArticle “Appropriate Treatment” and Therapeutic Window in Spasticity Treatment with IncobotulinumtoxinA: From 100 to 1000 Units
Received: 12 February 2018 / Revised: 21 March 2018 / Accepted: 23 March 2018 / Published: 28 March 2018
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Abstract
Many neurological diseases (ischemic and hemorrhagic stroke, multiple sclerosis, infant cerebral palsy, spinal cord injuries, traumatic brain injury, and other cerebrovascular disorders) may cause muscle spasticity. Different therapeutic strategies have been proposed for the treatment of spasticity. One of the major treatments for
[...] Read more.
Many neurological diseases (ischemic and hemorrhagic stroke, multiple sclerosis, infant cerebral palsy, spinal cord injuries, traumatic brain injury, and other cerebrovascular disorders) may cause muscle spasticity. Different therapeutic strategies have been proposed for the treatment of spasticity. One of the major treatments for tone modulation is botulinum toxin type A (BTX-A), performed in addition to other rehabilitation strategies based on individualized multidisciplinary programs aimed at achieving certain goals for each patient. Therapeutic plans must be precisely defined as they must balance the reduction of spastic hypertonia and retention of residual motor function. To perform and optimize the treatment, an accurate clinical and instrumental evaluation of spasticity is needed to determine how this symptom is invalidating and to choose the best doses, muscles and times of injection in each patient. We introduce an “appropriate treatment” and no “standard or high dosage treatment” concept based on our retrospective observational study on 120 patients lasting two years, according to the larger Therapeutic Index and Therapeutic Window of Incobotulinumtoxin A doses from 100 to 1000 units. We studied the efficiency and safety of this drug considering the clinical spasticity significance for specialist physicians and patients. Full article
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Open AccessFeature PaperArticle A Study and Review of Effects of Botulinum Toxins on Mast Cell Dependent and Independent Pruritus
Received: 7 March 2018 / Revised: 21 March 2018 / Accepted: 21 March 2018 / Published: 23 March 2018
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Abstract
Pruriceptive itch originates following activation of peripheral sensory nerve terminals when pruritogens come in contact with the skin. The ability of botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent terminals provides a rationale for studying its effect on pruritus. This study investigated
[...] Read more.
Pruriceptive itch originates following activation of peripheral sensory nerve terminals when pruritogens come in contact with the skin. The ability of botulinum neurotoxins (BoNTs) to attenuate transmitter release from afferent terminals provides a rationale for studying its effect on pruritus. This study investigated the effects of BoNT/A1 and BoNT/B1 on mast cell dependent (Compound 48/80:48/80) and independent (Chloroquine:CQ) scratching. C57Bl/6 male mice received intradermal injection of 1.5 U of BoNT/A1, BoNT/B1 or saline 2, 7, 14 and 21 days prior to ipsilateral 48/80 or CQ at the nape of the neck. Ipsilateral hind paw scratching was determined using an automated recording device. The effect of BoNTs on 48/80 mediated mast cell degranulation was analyzed in human and murine mast cells and the presence of SNAREs was determined using qPCR, immunostaining and Western blot. Pre-treatment with BoNT/A1 and BoNT/B1 reduced 48/80 and CQ induced scratching behavior starting on day 2 with reversal by day 21. Both serotypes inhibited 48/80 induced mast cell degranulation. qPCR and immunostaining detected SNAP-25 mRNA and protein, respectively, in mast cells, however, Western blots did not. This study demonstrates the long-lasting anti-pruritic effects of two BoNT serotypes, in a murine pruritus model using two different mechanistically driven pruritogens. These data also indicate that BoNTs may have a direct effect upon mast cell degranulation. Full article
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Open AccessArticle Botulinum Toxin B Affects Neuropathic Pain but Not Functional Recovery after Peripheral Nerve Injury in a Mouse Model
Received: 12 February 2018 / Revised: 13 March 2018 / Accepted: 15 March 2018 / Published: 18 March 2018
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Abstract
Clinical use of neurotoxins from Clostridium botulinum is well established and is continuously expanding, including in treatment of pain conditions. Background: The serotype A (BoNT/A) has been widely investigated, and current data demonstrate that it induces analgesia and modulates nociceptive processing initiated
[...] Read more.
Clinical use of neurotoxins from Clostridium botulinum is well established and is continuously expanding, including in treatment of pain conditions. Background: The serotype A (BoNT/A) has been widely investigated, and current data demonstrate that it induces analgesia and modulates nociceptive processing initiated by inflammation or nerve injury. Given that data concerning the serotype B (BoNT/B) are limited, the aim of the present study was to verify if also BoNT/B is able not only to counteract neuropathic pain, but also to interfere with inflammatory and regenerative processes associated with the nerve injury. Methods: As model of neuropathic pain, chronic constriction injury (CCI) of the sciatic nerve was performed in CD1 male mice. Mice were intraplantarly injected with saline (control) or BoNT/B (5 or 7.5 pg/mouse) into the injured hindpaw. For comparison, another mouse group was injected with BoNT/A (15 pg/mouse). Mechanical allodynia and functional recovery of the injured paw was followed for 101 days. Spinal cords and sciatic nerves were collected at day 7 for immunohistochemistry. Results and Conclusions: The results of this study show that BoNT/B is a powerful biological molecule that, similarly to BoNT/A, can reduce neuropathic pain over a long period of time. However, the analgesic effects are not associated with an improvement in functional recovery, clearly highlighting an important difference between the two serotypes for the treatment of this chronic pain state. Full article
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Open AccessArticle The Effect of Botulinum Neurotoxin Serotype a Heavy Chain on the Growth Related Proteins and Neurite Outgrowth after Spinal Cord Injury in Rats
Received: 23 November 2017 / Revised: 31 January 2018 / Accepted: 31 January 2018 / Published: 2 February 2018
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Abstract
(1) Background: The botulinum toxin A (BoNT-A) heavy chain (HC) can stimulate the growth of primary motor neurites. (2) Methods: A recombinant BoNT/A HC was injected locally plus interval intrathecal catheter of BoNT/A HC to rats with ipsilateral semi-dissociated lumbar spinal cord injuries
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(1) Background: The botulinum toxin A (BoNT-A) heavy chain (HC) can stimulate the growth of primary motor neurites. (2) Methods: A recombinant BoNT/A HC was injected locally plus interval intrathecal catheter of BoNT/A HC to rats with ipsilateral semi-dissociated lumbar spinal cord injuries (SCIs). First, 2D gel with a silver nitrate stain was applied to detect the general pattern of protein expression. Growth associated protein 43 (GAP-43) and superior cervical ganglion 10 (SCG10) were chosen to represent the altered proteins, based on their molecular weight and pI, and were used to further detect their expression. Meanwhile, the neuronal processes were measured. The measurements of thermal hyperalgesia and grasp power at the ipsilateral hindlimb were used to evaluate spinal sensory and motor function, respectively. (3) Results: The local injection of BoNT/A HC followed by its intrathecal catheter intervally altered the spinal protein expression pattern after an SCI; protein expression was similar to normal levels or displayed a remarkable increase. The changes in the expression and distribution of phosphorylated growth associated protein 43(p-GAP 43) and superior cervical ganglion 10 (SCG 10) indicated that the administration of BoNT/A HC to the SCI significantly amplified the expression of p-GAP43 and SCG10 (p < 0.05). Meanwhile, the positive immunofluorescent staining for both p-GAP43 and SCG10 was mainly present near the rostral aspect of the injury, both in the cytoplasm and the neuronal processes. Moreover, the outgrowth of neurites was stimulated by the BoNT/A HC treatment; this was evident from the increase in neurite length, number of branches and the percentage of cells with neuronal processes. The results from the spinal function tests suggested that the BoNT/A HC did not affect sensation, but had a large role in improving the ipsilateral hindlimb grasp power (p < 0.05). (4) Conclusions: The local injection with the intermittent intrathecal administration of BoNT/A heavy chain to rats with SCI increased the local expression of GAP-43 and SCG 10, which might be affiliated with the regeneration of neuronal processes surrounding the injury, and might also be favorable to the relief of spinal motor dysfunction. Full article
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Open AccessArticle Botulinum Toxin A for Sialorrhoea Associated with Neurological Disorders: Evaluation of the Relationship between Effect of Treatment and the Number of Glands Treated
Received: 21 December 2017 / Revised: 22 January 2018 / Accepted: 22 January 2018 / Published: 27 January 2018
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Abstract
Background: Sialorrhoea and drooling are disabling manifestations of different neurological disorders. The aim of this study was to evaluate the effects of botulinum neurotoxin type A (BoNT/A) injection on hypersalivation in 90 patients with neurological diseases of different aetiologies, and to define
[...] Read more.
Background: Sialorrhoea and drooling are disabling manifestations of different neurological disorders. The aim of this study was to evaluate the effects of botulinum neurotoxin type A (BoNT/A) injection on hypersalivation in 90 patients with neurological diseases of different aetiologies, and to define the minimum number of injected salivary glands to reduce sialorrhoea. Determining the minimum number of glands that need to be engaged in order to have a significant reduction in drooling may be very useful for establishing the minimum total dosage of BoNT/A that may be considered effective in the treatment of hypersalivation. Methods: Twenty-five mouse units (MU) of BoNT/A (onabotulinumtoxin A, Botox; Allergan, Irvine, CA, USA; 100 MU/2 mL, 0.9% saline; or incobotulinumtoxin A, Xeomin; Merz Pharma, Germany; 100 MU/2 mL, 0.9% saline) were percutaneously injected into the parotid (p) glands and/or submandibular (s) glands under ultrasound control. On this basis, patients were divided into three groups. In group A (30 patients), BoNT/A injections were performed into four glands; in group B (30 patients), into three glands, and in group C (30 patients), into two glands. Patients treated in three glands (group B) were divided into two subgroups based on the treated glands (2 p + 1 s = 15 patients; 2 s + 1 p = 15 patients). Similarly, patients being injected in two glands (group C) were subdivided into three groups (2 p = 10 patients; 1 p + 1 s = 10 patients; 2 s = 10 patients). In patients who were injected in three and two salivary glands, saline solution was injected into the remaining one and two glands, respectively. Assessments were performed at baseline and at 2 weeks after the injections. Results: BoNT/A significantly reduced sialorrhoea in 82 out of 90 patients. The effect was more evident in patients who had four glands injected than when three or two glands were injected. The injections into three glands were more effective than injections into two glands. Conclusions: Our results have shown that BoNT/A injections induced a significant reduction in sialorrhoea in most patients (91%). In addition, we demonstrated that sialorrhoea associated with different neurological diseases was better controlled when the number of treated glands was higher. Full article
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Review

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Open AccessReview The Expanding Therapeutic Utility of Botulinum Neurotoxins
Received: 13 April 2018 / Revised: 15 May 2018 / Accepted: 16 May 2018 / Published: 18 May 2018
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Abstract
Botulinum neurotoxin (BoNT) is a major therapeutic agent that is licensed in neurological indications, such as dystonia and spasticity. The BoNT family, which is produced in nature by clostridial bacteria, comprises several pharmacologically distinct proteins with distinct properties. In this review, we present
[...] Read more.
Botulinum neurotoxin (BoNT) is a major therapeutic agent that is licensed in neurological indications, such as dystonia and spasticity. The BoNT family, which is produced in nature by clostridial bacteria, comprises several pharmacologically distinct proteins with distinct properties. In this review, we present an overview of the current therapeutic landscape and explore the diversity of BoNT proteins as future therapeutics. In recent years, novel indications have emerged in the fields of pain, migraine, overactive bladder, osteoarthritis, and wound healing. The study of biological effects distal to the injection site could provide future opportunities for disease-tailored BoNT therapies. However, there are some challenges in the pharmaceutical development of BoNTs, such as liquid and slow-release BoNT formulations; and, transdermal, transurothelial, and transepithelial delivery. Innovative approaches in the areas of formulation and delivery, together with highly sensitive analytical tools, will be key for the success of next generation BoNT clinical products. Full article
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Open AccessFeature PaperReview Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology
Received: 31 March 2018 / Revised: 21 April 2018 / Accepted: 23 April 2018 / Published: 25 April 2018
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Abstract
Botulinum neurotoxins are metalloproteases that specifically cleave N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in synaptic terminals, resulting in a potent inhibition of vesicle fusion and transmitter release. The family comprises different serotypes (BoNT/A to BoNT/G). The natural target of these toxins
[...] Read more.
Botulinum neurotoxins are metalloproteases that specifically cleave N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in synaptic terminals, resulting in a potent inhibition of vesicle fusion and transmitter release. The family comprises different serotypes (BoNT/A to BoNT/G). The natural target of these toxins is represented by the neuromuscular junction, where BoNTs block acetylcholine release. In this review, we describe the actions of botulinum toxins after direct delivery to the central nervous system (CNS), where BoNTs block exocytosis of several transmitters, with near-complete silencing of neural networks. The use of clostridial neurotoxins in the CNS has allowed us to investigate specifically the role of synaptic activity in different physiological and pathological processes. The silencing properties of BoNTs can be exploited for therapeutic purposes, for example to counteract pathological hyperactivity and seizures in epileptogenic brain foci, or to investigate the role of activity in degenerative diseases like prion disease. Altogether, clostridial neurotoxins and their derivatives hold promise as powerful tools for both the basic understanding of brain function and the dissection and treatment of activity-dependent pathogenic pathways. Full article
Open AccessReview Therapeutic Approaches of Botulinum Toxin in Gynecology
Received: 31 March 2018 / Revised: 18 April 2018 / Accepted: 19 April 2018 / Published: 21 April 2018
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Abstract
Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been
[...] Read more.
Botulinum toxins (BoNTs) are produced by several anaerobic species of the genus Clostridium and, although they were originally considered lethal toxins, today they find their usefulness in the treatment of a wide range of pathologies in various medical specialties. Botulinum neurotoxin has been identified in seven different isoforms (BoNT-A, BoNT-B, BoNT-C, BoNT-D, BoNT-E, BoNT-F, and BoNT-G). Neurotoxigenic Clostridia can produce more than 40 different BoNT subtypes and, recently, a new BoNT serotype (BoNT-X) has been reported in some studies. BoNT-X has not been shown to actually be an active neurotoxin despite its catalytically active LC, so it should be described as a putative eighth serotype. The mechanism of action of the serotypes is similar: they inhibit the release of acetylcholine from the nerve endings but their therapeutically potency varies. Botulinum toxin type A (BoNT-A) is the most studied serotype for therapeutic purposes. Regarding the gynecological pathology, a series of studies based on the efficiency of its use in the treatment of refractory myofascial pelvic pain, vaginism, dyspareunia, vulvodynia and overactive bladder or urinary incontinence have been reported. The current study is a review of the literature regarding the efficiency of BoNT-A in the gynecological pathology and on the long and short-term effects of its administration. Full article
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Open AccessReview Analgesic Effects of Botulinum Toxin in Children with CP
Received: 30 March 2018 / Revised: 12 April 2018 / Accepted: 13 April 2018 / Published: 19 April 2018
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Abstract
Experiencing pain is the greatest contributor to a reduced quality of life in children with cerebral palsy (CP). The presence of pain is quite common (~60%) and increases with age. This leads to missed school days, less participation, and reduced ambulation. Despite these
[...] Read more.
Experiencing pain is the greatest contributor to a reduced quality of life in children with cerebral palsy (CP). The presence of pain is quite common (~60%) and increases with age. This leads to missed school days, less participation, and reduced ambulation. Despite these alarming consequences, strategies to relieve the pain are absent and poorly studied. Moreover, it is difficult to evaluate pain in this group of children, especially in cases of children with cognitive deficits, and tools for pain evaluation are often inadequate. Botulinum toxin has been shown to alleviate pain in a variety of disorders and could potentially have an analgesic effect in children with CP as well. Even though most of the studies presented here show promising results, many also have limitations in their methodology as it is unlikely to capture all dimensions of pain in this heterogeneous group using only one assessment tool. In this review, we present a new way of examining the analgesic effect of botulinum toxin in children with CP using a variety of pain scores. Full article
Open AccessFeature PaperReview Botulinum Toxin Type A—A Modulator of Spinal Neuron–Glia Interactions under Neuropathic Pain Conditions
Received: 9 March 2018 / Revised: 27 March 2018 / Accepted: 30 March 2018 / Published: 2 April 2018
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Abstract
Neuropathic pain represents a significant clinical problem because it is a chronic condition often refractory to available therapy. Therefore, there is still a strong need for new analgesics. Botulinum neurotoxin A (BoNT/A) is used to treat a variety of clinical diseases associated with
[...] Read more.
Neuropathic pain represents a significant clinical problem because it is a chronic condition often refractory to available therapy. Therefore, there is still a strong need for new analgesics. Botulinum neurotoxin A (BoNT/A) is used to treat a variety of clinical diseases associated with pain. Glia are in continuous bi-directional communication with neurons to direct the formation and refinement of synaptic connectivity. This review addresses the effects of BoNT/A on the relationship between glia and neurons under neuropathic pain. The inhibitory action of BoNT/A on synaptic vesicle fusion that blocks the release of miscellaneous pain-related neurotransmitters is known. However, increasing evidence suggests that the analgesic effect of BoNT/A is mediated through neurons and glial cells, especially microglia. In vitro studies provide evidence that BoNT/A exerts its anti-inflammatory effect by diminishing NF-κB, p38 and ERK1/2 phosphorylation in microglia and directly interacts with Toll-like receptor 2 (TLR2). Furthermore, BoNT/A appears to have no more than a slight effect on astroglia. The full activation of TLR2 in astroglia appears to require the presence of functional TLR4 in microglia, emphasizing the significant interaction between those cell types. In this review, we discuss whether and how BoNT/A affects the spinal neuron–glia interaction and reduces the development of neuropathy. Full article
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Open AccessFeature PaperReview Antipruritic Effects of Botulinum Neurotoxins
Received: 5 March 2018 / Revised: 27 March 2018 / Accepted: 27 March 2018 / Published: 29 March 2018
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Abstract
This review explores current evidence to demonstrate that botulinum neurotoxins (BoNTs) exert antipruritic effects. Both experimental and clinical conditions in which botulinum neurotoxins have been applied for pruritus relief will be presented and significant findings will be highlighted. Potential mechanisms underlying antipruritic effects
[...] Read more.
This review explores current evidence to demonstrate that botulinum neurotoxins (BoNTs) exert antipruritic effects. Both experimental and clinical conditions in which botulinum neurotoxins have been applied for pruritus relief will be presented and significant findings will be highlighted. Potential mechanisms underlying antipruritic effects will also be discussed and ongoing challenges and unmet needs will be addressed. Full article
Open AccessReview Correction of Malocclusion by Botulinum Neurotoxin Injection into Masticatory Muscles
Received: 1 December 2017 / Revised: 29 December 2017 / Accepted: 31 December 2017 / Published: 2 January 2018
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Abstract
Botulinum toxin (BTX) is a neurotoxin, and its injection in masticatory muscles induces muscle weakness and paralysis. This paralytic effect of BTX induces growth retardation of the maxillofacial bones, changes in dental eruption and occlusion state, and facial asymmetry. Using masticatory muscle paralysis
[...] Read more.
Botulinum toxin (BTX) is a neurotoxin, and its injection in masticatory muscles induces muscle weakness and paralysis. This paralytic effect of BTX induces growth retardation of the maxillofacial bones, changes in dental eruption and occlusion state, and facial asymmetry. Using masticatory muscle paralysis and its effect via BTX, BTX can be used for the correction of malocclusion after orthognathic surgery and mandible fracture. The paralysis of specific masticatory muscles by BTX injection reduces the tensional force to the mandible and prevents relapse and changes in dental occlusion. BTX injection in the anterior belly of digastric and mylohyoid muscle prevents the open-bite and deep bite of dental occlusion and contributes to mandible stability after orthognathic surgery. The effect of BTX injection in masticatory muscles for maxillofacial bone growth and dental occlusion is reviewed in this article. The clinical application of BTX is also discussed for the correction of dental malocclusion and suppression of post-operative relapse after mandibular surgery. Full article
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Open AccessReview Botulinum Toxin in the Field of Dermatology: Novel Indications
Toxins 2017, 9(12), 403; https://doi.org/10.3390/toxins9120403
Received: 20 November 2017 / Revised: 13 December 2017 / Accepted: 14 December 2017 / Published: 16 December 2017
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Abstract
Since its approval by the US Food and Drug Administration in 2002 for glabellar wrinkles, botulinum toxin (BTX) has been widely used to correct facial wrinkles. As a result, many consider BTX synonymous with cosmetic dermatology. Recent studies indicate that BTX elicits biological
[...] Read more.
Since its approval by the US Food and Drug Administration in 2002 for glabellar wrinkles, botulinum toxin (BTX) has been widely used to correct facial wrinkles. As a result, many consider BTX synonymous with cosmetic dermatology. Recent studies indicate that BTX elicits biological effects on various skin cell types via the modulation of neurotransmitter release, and it seems that BTX has a wider zone of dermatologic influence than originally understood. Clinicians and researchers are now beginning to explore the potential of BTX beyond the amelioration of facial lines and encouraging results are seen with BTX in a variety of skin conditions. In this paper, we review novel dermatological indications of BTX which includes (but not limited to) scar prevention, facial flushing, post-herpetic neuralgia and itch. These areas show great promise, but there is definite need for larger, double-blinded, randomized control trials against established treatments before BTX becomes a clinical reality. Full article
Open AccessFeature PaperEditor’s ChoiceReview Botulinum Toxin in Management of Limb Tremor
Toxins 2017, 9(11), 365; https://doi.org/10.3390/toxins9110365
Received: 24 October 2017 / Revised: 7 November 2017 / Accepted: 8 November 2017 / Published: 10 November 2017
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Abstract
Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one’s ability to perform daily tasks becomes impaired. Oral
[...] Read more.
Essential tremor is characterized by persistent, usually bilateral and symmetric, postural or kinetic activation of agonist and antagonist muscles involving either the distal or proximal upper extremity. Quality of life is often affected and one’s ability to perform daily tasks becomes impaired. Oral therapies, including propranolol and primidone, can be effective in the management of essential tremor, although adverse effects can limit their use and about 50% of individuals lack response to oral pharmacotherapy. Locally administered botulinum toxin injection has become increasingly useful in the management of essential tremor. Targeting of select muscles with botulinum toxin is an area of active research, and muscle selection has important implications for toxin dosing and functional outcomes. The use of anatomical landmarks with palpation, EMG guidance, electrical stimulation, and ultrasound has been studied as a technique for muscle localization in toxin injection. Earlier studies implemented a standard protocol for the injection of (predominantly) wrist flexors and extensors using palpation and EMG guidance. Targeting of muscles by selection of specific activators of tremor (tailored to each patient) using kinematic analysis might allow for improvement in efficacy, including functional outcomes. It is this individualized muscle selection and toxin dosing (requiring injection within various sites of a single muscle) that has allowed for success in the management of tremors. Full article
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