Botulinum Toxins: New Uses in the Treatment of Diseases

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

Deadline for manuscript submissions: closed (10 April 2023) | Viewed by 55752

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Institute of Biochemistry and Cell Biology, National Council of Research of Italy, Via Ercole Ramarini 32, 00015 Monterotondo, Italy
Interests: botulinum neurotoxins; neuropathic pain; peripheral nerve; motor function; functional recovery; animal model; glial cells; Schwann cells
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Dear Colleagues,

Both animal and clinical studies have extensively reported the therapeutic efficacy of botulinum neurotoxins (BoNTs) in many diseases characterized by excessive muscle contractions. Since the therapeutic effects of BoNTs reside in their elective action as inhibitors of cholinergic transmission, this has given extraordinary support to the clinical use of BoNTs in pathologies such as dystonia, torticollis, blepharospasm, and many others originating from hypercholinergic dysfunctions. Today, the list of human pathologies in which treatment with BoNTs produces favorable results is constantly growing. This Special Issue, entitled “Botulinum Neurotoxins: Employ in the Treatment of Diseases”, is particularly dedicated to the collection of research on new therapeutic applications of BoNTs, both as native and engineered toxins. Both review and research articles on animal models, clinical studies, case reports, or off-label indications are welcome. The ambitious goal of this Special Issue is to provide an updated framework on the development of new applications of BoNTs for their future clinical use.

Dr. Siro Luvisetto
Guest Editor

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Keywords

  • botulinum toxin
  • mechanism of action
  • animal models
  • human diseases
  • clinical study
  • case report
  • off-label use
  • new indications
  • engineered toxins

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Published Papers (14 papers)

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Editorial

Jump to: Research, Review

4 pages, 224 KiB  
Editorial
Introduction to the Toxins Special Issue on Botulinum Toxins: New Uses in the Treatment of Diseases
by Siro Luvisetto
Toxins 2023, 15(9), 540; https://doi.org/10.3390/toxins15090540 - 1 Sep 2023
Viewed by 978
Abstract
Studies on animals and humans have amply demonstrated the therapeutic efficacy of botulinum neurotoxins (BoNTs) in many pathologies [...] Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)

Research

Jump to: Editorial, Review

13 pages, 5837 KiB  
Article
Efficacy of Intra-Articular Injection of Botulinum Toxin Type A (IncobotulinumtoxinA) in Temporomandibular Joint Osteoarthritis: A Three-Arm Controlled Trial in Rats
by Marie Béret, Florent Barry, Maria-Jose Garcia-Fernandez, Henry Chijcheapaza-Flores, Nicolas Blanchemain, Feng Chai and Romain Nicot
Toxins 2023, 15(4), 261; https://doi.org/10.3390/toxins15040261 - 1 Apr 2023
Cited by 2 | Viewed by 1986
Abstract
Temporomandibular disorders (TMD) are complex pathologies responsible for chronic orofacial pain. Intramuscular injection of botulinum toxin A (BoNT/A) has shown effectiveness in knee and shoulder osteoarthritis, as well as in some TMDs such as masticatory myofascial pain, but its use remains controversial. This [...] Read more.
Temporomandibular disorders (TMD) are complex pathologies responsible for chronic orofacial pain. Intramuscular injection of botulinum toxin A (BoNT/A) has shown effectiveness in knee and shoulder osteoarthritis, as well as in some TMDs such as masticatory myofascial pain, but its use remains controversial. This study aimed to evaluate the effect of intra-articular BoNT/A injection in an animal model of temporomandibular joint osteoarthritis. A rat model of temporomandibular osteoarthritis was used to compare the effects of intra-articular injection of BoNT/A, placebo (saline), and hyaluronic acid (HA). Efficacy was compared by pain assessment (head withdrawal test), histological analysis, and imaging performed in each group at different time points until day 30. Compared with the rats receiving placebo, those receiving intra-articular BoNT/A and HA had a significant decrease in pain at day 14. The analgesic effect of BoNT/A was evident as early as day 7, and lasted until day 21. Histological and radiographic analyses showed decrease in joint inflammation in the BoNT/A and HA groups. The osteoarthritis histological score at day 30 was significantly lower in the BoNT/A group than in the other two groups (p = 0.016). Intra-articular injection of BoNT/A appeared to reduce pain and inflammation in experimentally induced temporomandibular osteoarthritis in rats. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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11 pages, 3027 KiB  
Article
Xeomin®, a Commercial Formulation of Botulinum Neurotoxin Type A, Promotes Regeneration in a Preclinical Model of Spinal Cord Injury
by Valentina Mastrorilli, Federica De Angelis, Valentina Vacca, Flaminia Pavone, Siro Luvisetto and Sara Marinelli
Toxins 2023, 15(4), 248; https://doi.org/10.3390/toxins15040248 - 28 Mar 2023
Cited by 4 | Viewed by 1595
Abstract
Xeomin® is a commercial formulation of botulinum neurotoxin type A (BoNT/A) clinically authorized for treating neurological disorders, such as blepharospasm, cervical dystonia, limb spasticity, and sialorrhea. We have previously demonstrated that spinal injection of laboratory purified 150 kDa BoNT/A in paraplegic mice, [...] Read more.
Xeomin® is a commercial formulation of botulinum neurotoxin type A (BoNT/A) clinically authorized for treating neurological disorders, such as blepharospasm, cervical dystonia, limb spasticity, and sialorrhea. We have previously demonstrated that spinal injection of laboratory purified 150 kDa BoNT/A in paraplegic mice, after undergoing traumatic spinal cord injury (SCI), was able to reduce excitotoxic phenomena, glial scar, inflammation, and the development of neuropathic pain and facilitate regeneration and motor recovery. In the present study, as proof of concept in view of a possible clinical application, we studied the efficacy of Xeomin® in the same preclinical SCI model in which we highlighted the positive effects of lab-purified BoNT/A. Data comparison shows that Xeomin® induces similar pharmacological and therapeutic effects, albeit with less efficacy, to lab-purified BoNT/A. This difference, which can be improved by adjusting the dose, can be attributable to the different formulation and pharmacodynamics. Although the mechanism by which Xeomin® and laboratory purified BoNT/A induce functional improvement in paraplegic mice is still far from being understood, these results open a possible new scenario in treatment of SCI and are a stimulus for further research. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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8 pages, 1065 KiB  
Article
Real-Time Documentation of the Effect of Onabotulinumtoxin A Detrusor Injection in OAB Patients—Preliminary Results
by Heinrich Schulte-Baukloh, Catarina Weiß, Sarah Weinberger, Mandy Hubatsch, Thorsten Schlomm and Bernhard Ralla
Toxins 2023, 15(1), 30; https://doi.org/10.3390/toxins15010030 - 30 Dec 2022
Cited by 2 | Viewed by 1305
Abstract
Introduction: Detrusor injection with onabotulinumtoxin A (OnabotA-DI) is an established therapy for overactive bladder (OAB). Little is known about the exact onset and course of the effect in the days after the injection therapy. By using a new type of app-controlled automated diary [...] Read more.
Introduction: Detrusor injection with onabotulinumtoxin A (OnabotA-DI) is an established therapy for overactive bladder (OAB). Little is known about the exact onset and course of the effect in the days after the injection therapy. By using a new type of app-controlled automated diary pod, for the first time, the precise onset of the effect of OnabotA-DI can be documented in real time. Materials and methods: Patients due for OnabotA-DI were asked to document voiding 3 days before and up to 3 weeks after therapy using the Diary Pod app. The detrusor injection was performed with onabotulinumtoxin A (Botox®), 100 units, at 20 sites of the detrusor muscle in a standardized manner. Voiding on the injection day itself was not documented. Results: A total of 17 patients (15 women, 2 men; aged 33–83 (mean 64.6; median 70) years) were included in the study. The handling of the Diary Pod app was user-friendly, and elderly patients did not encounter technical problems. The results of patients with reliably documented micturitions showed a continuous reduction in micturition frequency every day from the first day and significantly from day 5. For 24 h voiding, from 12.83 ± 5.54 in the 3 days before injection, the following mean values were found with significant (p < 0.05) changes after the intervention: 9.17 ± 3.19 on day 5, 8.75 ± 3.69 on day 10, 7.17 ± 2.04 on day 15, and 5.75 ± 0.5 on day 20. These changes were in similar proportions during the daytime and nighttime. Conclusions: Contrary to previous knowledge, the effect of the OnabotA-DI set in from the first postoperative days and was reflected a similar extent in day and night micturition. This study is the first to document the onset of action of OnabotA-DI in real time. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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12 pages, 876 KiB  
Article
Prediction Model for Identifying Computational Phenotypes of Children with Cerebral Palsy Needing Neurotoxin Treatments
by Carlo M. Bertoncelli, Michal Latalski, Domenico Bertoncelli, Sikha Bagui, Subhash C. Bagui, Dechelle Gautier and Federico Solla
Toxins 2023, 15(1), 20; https://doi.org/10.3390/toxins15010020 - 28 Dec 2022
Cited by 1 | Viewed by 1986
Abstract
Factors associated with neurotoxin treatments in children with cerebral palsy (CP) are poorly studied. We developed and externally validated a prediction model to identify the prognostic phenotype of children with CP who require neurotoxin injections. We conducted a longitudinal, international, multicenter, double-blind descriptive [...] Read more.
Factors associated with neurotoxin treatments in children with cerebral palsy (CP) are poorly studied. We developed and externally validated a prediction model to identify the prognostic phenotype of children with CP who require neurotoxin injections. We conducted a longitudinal, international, multicenter, double-blind descriptive study of 165 children with CP (mean age 16.5 ± 1.2 years, range 12–18 years) with and without neurotoxin treatments. We collected functional and clinical data from 2005 to 2020, entered them into the BTX-PredictMed machine-learning model, and followed the guidelines, “Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis”. In the univariate analysis, neuromuscular scoliosis (p = 0.0014), equines foot (p < 0.001) and type of etiology (prenatal > peri/postnatal causes, p = 0.05) were linked with neurotoxin treatments. In the multivariate analysis, upper limbs (p < 0.001) and trunk muscle tone disorders (p = 0.02), the presence of spasticity (p = 0.01), dystonia (p = 0.004), and hip dysplasia (p = 0.005) were strongly associated with neurotoxin injections; and the average accuracy, sensitivity, and specificity was 75%. These results have helped us identify, with good accuracy, the clinical features of prognostic phenotypes of subjects likely to require neurotoxin injections. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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11 pages, 746 KiB  
Article
Frequency of Hemorrhagic Side Effects of Botulinum Neurotoxin Treatment in Patients with Blepharospasm and Hemifacial Spasm on Antithrombotic Medication
by Fiona Carolin Wenninger and Bettina Wabbels
Toxins 2022, 14(11), 769; https://doi.org/10.3390/toxins14110769 - 7 Nov 2022
Cited by 2 | Viewed by 1693
Abstract
The aim of this study was to investigate the frequency of hemorrhagic side effects of botulinum neurotoxin A injections (BoNT/A) for the treatment of benign essential blepharospasm (BEB) and hemifacial spasm (HFS) in patients taking antithrombotic drugs (ATD). A total of 140 patients [...] Read more.
The aim of this study was to investigate the frequency of hemorrhagic side effects of botulinum neurotoxin A injections (BoNT/A) for the treatment of benign essential blepharospasm (BEB) and hemifacial spasm (HFS) in patients taking antithrombotic drugs (ATD). A total of 140 patients were included (female: 65%; BEB: 75%; mean age: 70 ± 12 years). According to their current antithrombotic medication, participants were either assigned to the ATD group (41%), or to the control group (59%). The ATD group was further divided into subgroups depending on the medication administered: acetylsalicylic acid, ADP receptor antagonists, direct oral anticoagulants, vitamin-K antagonists, or dual antiplatelet therapy. The frequency of hemorrhagic side effects was recorded by retrospective analysis of past treatments as documented in the patient’s file set in relation to the number of past treatments (hematoma frequency of past treatments, HFretro) as well as by a prospective survey capturing the side effects of one single treatment (hematoma frequency of actual treatment, HFactual). There was no significant difference in hematoma frequency between the ATD group and the control group, neither for past (HFretro: ATD: 2%; 45/2554; control: 4%; 109/2744) nor for the current BoNT/A treatments (HFactual: ATD: 30%; 16/53; control: 31%; 22/72). Even between ATD subgroups, hematoma frequency did not differ significantly. Overall, hemorrhagic side effects of the BoNT/A treatment for BEB and HFS were mild and non-disabling. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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20 pages, 3719 KiB  
Article
Can Botulinum Toxin-A Contribute to Reconstructing the Physiological Homeostasis of the Masticatory Complex in Short-Faced Patients during Occlusal Therapy? A Prospective Pilot Study
by Xin Li, Xiaoyan Feng, Juan Li, Xinyu Bao, Jinghong Xu and Jun Lin
Toxins 2022, 14(6), 374; https://doi.org/10.3390/toxins14060374 - 28 May 2022
Cited by 3 | Viewed by 3202
Abstract
The physiological homeostasis of the masticatory complex in short-faced patients is too robust to be disintegrated and reconstructed due to the powerful masseter muscle. This study innovatively introduced the botulinum toxin-A (BTX-A) into the field of dental occlusal treatment, providing a novel and [...] Read more.
The physiological homeostasis of the masticatory complex in short-faced patients is too robust to be disintegrated and reconstructed due to the powerful masseter muscle. This study innovatively introduced the botulinum toxin-A (BTX-A) into the field of dental occlusal treatment, providing a novel and minimally invasive therapy perspective for the two major clinical problems in these patients (low treatment efficiency and high rates of complications). In total, 10 adult patients with skeletal low angle seeking occlusal treatment (age: 27.0 ± 6.1 years; 4 males and 6 females) were administered 30–50 U of BTX-A in each masseter muscle and evaluated before and 3 months after injection based on cone-beam computed tomography (CBCT). We found a significant reduction in the thickness of the masseter muscle (MMT) (p < 0.0001). With regards to occlusion, we found a significant increase in the height of the maxillary second molar (U7-PP) (p < 0.05) with significantly flattened occlusal curves (the curve of Spee [COS] (p < 0.01), and the curve of Wilson [COW] (p < 0.05)). Furthermore, the variations in the temporomandibular joint exhibited a significant reduction in the anterior joint space (AJS) (p < 0.05) and superior joint space (SJS) (p < 0.05). In addition, the correlation analysis of the masticatory complex provided the basis for the following multiple regression equation: MMT = 10.08 − 0.11 COW + 2.73 AJS. The findings from our pilot study indicate that BTX-A, as a new adjuvant treatment attempt of occlusal therapy for short-faced patients, can provide a more favorable muscular environment for subsequent occlusal therapy through the adjustment of the biting force and may contribute to the reconstruction of healthier homeostasis of the masticatory complex. However, further research is required to establish the reliability and validity of these findings. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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9 pages, 1840 KiB  
Article
Intramuscular Neural Distribution of the Serratus Anterior Muscle: Regarding Botulinum Neurotoxin Injection for Treating Myofascial Pain Syndrome
by Kyu-Ho Yi, Ji-Hyun Lee and Hee-Jin Kim
Toxins 2022, 14(4), 271; https://doi.org/10.3390/toxins14040271 - 11 Apr 2022
Cited by 14 | Viewed by 4712
Abstract
The serratus anterior muscle is commonly involved in myofascial pain syndrome and is treated with many different injective methods. Currently, there is no definite injection point for the muscle. This study provides a suggestion for injection points for the serratus anterior muscle considering [...] Read more.
The serratus anterior muscle is commonly involved in myofascial pain syndrome and is treated with many different injective methods. Currently, there is no definite injection point for the muscle. This study provides a suggestion for injection points for the serratus anterior muscle considering the intramuscular neural distribution using the whole-mount staining method. A modified Sihler method was applied to the serratus anterior muscles (15 specimens). The intramuscular arborization areas were identified in terms of the anterior (100%), middle (50%), and posterior axillary line (0%), and from the first to the ninth ribs. The intramuscular neural distribution for the serratus anterior muscle had the largest arborization patterns in the fifth to the ninth rib portion of between 50% and 70%, and the first to the fourth rib portion had between 20% and 40%. These intramuscular neural distribution-based injection sites are in relation to the external anatomical line for the frequently injected muscles to facilitate the efficiency of botulinum neurotoxin injections. Lastly, the intramuscular neural distribution of serratus anterior muscle should be considered in order to practice more accurately without the harmful side effects of trigger-point injections and botulinum neurotoxin injections. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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17 pages, 3018 KiB  
Article
Antinociceptive Actions of Botulinum Toxin A1 on Immunogenic Hypersensitivity in Temporomandibular Joint of Rats
by Victor Ricardo Manuel Muñoz-Lora, Ana Dugonjić Okroša, Ivica Matak, Altair Antoninha Del Bel Cury, Mikhail Kalinichev and Zdravko Lacković
Toxins 2022, 14(3), 161; https://doi.org/10.3390/toxins14030161 - 23 Feb 2022
Cited by 7 | Viewed by 2881
Abstract
Botulinum neurotoxin type A1 (BoNT-A) reduces the peripheral peptide and cytokine upregulation in rats with antigen-evoked persistent immunogenic hypersensitivity (PIH) of the temporomandibular joint (TMJ). Herein, we examined the effects of two preparations of BoNT-A, abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox), on [...] Read more.
Botulinum neurotoxin type A1 (BoNT-A) reduces the peripheral peptide and cytokine upregulation in rats with antigen-evoked persistent immunogenic hypersensitivity (PIH) of the temporomandibular joint (TMJ). Herein, we examined the effects of two preparations of BoNT-A, abobotulinumtoxinA (aboBoNT-A; Dysport) and onabotulinumtoxinA (onaBoNT-A; Botox), on spontaneous and evoked nociceptive behaviors, as well as on central neuronal and astroglial activation. The antigen-evoked PIH was induced in rats via repeated systemic and unilateral intra-articular (i.a.) injections of methylated bovine serum albumin (mBSA). Rats were subsequently injected with unilateral i.a. aboBoNT-A (14 U/kg), onaBoNT-A (7 U/kg), or the vehicle (saline). After i.a. treatments, spontaneous and mechanically evoked nocifensive behaviors were assessed before and after the low-dose i.a. formalin (0.5%) challenge. The central effects of BoNT-A were assessed by an immunohistochemical analysis of cleaved synaptosomal-associated protein 25 (cSNAP-25) presence, c-Fos, GFAP, and CGRP expression in the trigeminal nucleus caudalis (TNC). Both BoNT-A preparations similarly reduced the formalin-induced spontaneous pain-related behaviors and mechanical allodynia of the hypernociceptive rats. Likewise, their effects were associated with the central occurrence of cSNAP-25 and reduction of c-Fos and GFAP upregulation in the TNC. BoNT-A antinociceptive activity on the PIH is associated with the toxin axonal transport to trigeminal sensory areas and reduction of neuronal and glial activation in central nociceptive regions. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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6 pages, 241 KiB  
Article
Safety of High-Dose Botulinum Toxin Injections for Parotid and Submandibular Gland Radioprotection
by Joerg Mueller, Thomas Langbein, Aditi Mishra and Richard P. Baum
Toxins 2022, 14(1), 64; https://doi.org/10.3390/toxins14010064 - 17 Jan 2022
Cited by 11 | Viewed by 3701
Abstract
Botulinum Toxin injections into salivary glands (SG) up to a total dose of 100 units IncobotulinumtoxinA (IncoA) represent the treatment of choice for sialorrhea. However, BTX might also protect SG against sialotoxic radioligand cancer therapies. The radioligand Actinium-225-PSMA effectively targets Prostate Cancer (PCa) [...] Read more.
Botulinum Toxin injections into salivary glands (SG) up to a total dose of 100 units IncobotulinumtoxinA (IncoA) represent the treatment of choice for sialorrhea. However, BTX might also protect SG against sialotoxic radioligand cancer therapies. The radioligand Actinium-225-PSMA effectively targets Prostate Cancer (PCa) metastases but inevitably destroys SG due to unintended gland uptake. A preliminary case series with regular-dose IncoA failed to reduce SG PSMA-radioligand uptake. We therefore increased IncoA dosage in combination with transdermal scopolamine until a clinically relevant SG PSMA-radioligand uptake reduction was achieved. Ten consecutive men with metastasized PCa refractory to all other cancer therapies received gradually increasing IncoA dosages as part of a compassionate use PSMA-radioligand-therapy trial. The parotid gland received six and the submandibular gland three injection points under ultrasound control, up to a maximum of 30 units IncoA per injection point. A maximum total dose of 250 units IncoA was applied with up to 170 units per parotid and 80 units per submandibular gland. Treatment was well tolerated and all side-effects were non-serious. The most frequent side-effect was dry mouth of mild severity. No dysphagia, facial weakness, chewing difficulties or systemic side-effects were observed. SG injections with IncoA up to a total dose of 250 units are safe when distributed among several injection-points under ultrasound control by an experienced physician. These preliminary findings lay the basis for future trials including BTX as major component for SG protection in established as well as newly emerging radioligand cancer therapies. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)

Review

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12 pages, 697 KiB  
Review
Botulinum Neurotoxins beyond Neurons: Interplay with Glial Cells
by Siro Luvisetto
Toxins 2022, 14(10), 704; https://doi.org/10.3390/toxins14100704 - 13 Oct 2022
Cited by 11 | Viewed by 3364
Abstract
In recent years, numerous studies have highlighted the significant use of botulinum neurotoxins (BoNTs) in the human therapy of various motor and autonomic disorders. The therapeutic action is exerted with the selective cleavage of specific sites of the SNARE’s protein complex, which plays [...] Read more.
In recent years, numerous studies have highlighted the significant use of botulinum neurotoxins (BoNTs) in the human therapy of various motor and autonomic disorders. The therapeutic action is exerted with the selective cleavage of specific sites of the SNARE’s protein complex, which plays a key role in the vesicular neuroexocytosis which is responsible for neural transmission. The primary target of the BoNTs’ action is the peripheral neuromuscular junction (NMJ), where, by blocking cholinergic neurons releasing acetylcholine (ACh), they interfere with neural transmission. A great deal of experimental evidence has demonstrated that BoNTs are also effective in blocking the release of other neurotransmitters or neuromodulators, such as glutamate, substance-P, and CGRP, and they can interfere with the function of glial cells, both at the peripheral and central level. The purpose of this review is to provide an update on the available experimental data from animal models that suggest or confirm the direct interactions between BoNTs and glial cells. From the data collected, it appears evident that, through mechanisms that are not yet fully understood, BoNTs can block the activation of spinal glial cells and their subsequent release of pro-inflammatory factors. BoNTs are also able to promote peripheral regeneration processes after nerve injury by stimulating the proliferation of Schwann cells. The data will be discussed in consideration of the possible therapeutic implications of the use of BoNTs on those pathological conditions where the contribution of glial cell activation is fundamental, such as in peripheral and central neuropathies. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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22 pages, 2459 KiB  
Review
How Does Botulinum Toxin Inhibit Itch?
by Parisa Gazerani
Toxins 2022, 14(10), 701; https://doi.org/10.3390/toxins14100701 - 12 Oct 2022
Cited by 2 | Viewed by 9212
Abstract
Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and most clinical case reports still focus on the off-label use of BoNTs for various itchy conditions. Few randomized [...] Read more.
Two decades after reports of the anti-pruritic effects of botulinum neurotoxins (BoNTs), there is still no approved product for the anti-itch indication of BoNTs, and most clinical case reports still focus on the off-label use of BoNTs for various itchy conditions. Few randomized clinical trials have been conducted with controversial results, and the beneficial effects of BoNTs against itch are mainly based on case studies and case series. These studies are valuable in presenting the potential application of BoNTs in chronic pruritic conditions, but due to the nature of these studies, they are categorized as providing lower levels of evidence or lower grades of recommendation. To obtain approval for the anti-pruritic indication of BoNTs, higher levels of evidence are required, which can be achieved through conducting large-scale and well-designed studies with proper control groups and established careful and reliable primary and secondary outcomes. In addition to clinical evidence, presenting the mechanism-based antipruritic action of BoNTs can potentially strengthen, accelerate, and facilitate the current efforts towards further investments in accelerating the field towards the potential approval of BoNTs for itchy conditions. This review, therefore, aimed to provide the state-of-the-art mechanisms underlying the anti-itch effect of BoNTs from basic studies that resemble various clinical conditions with itch as a hallmark. Evidence of the neuronal, glial, and immune modulatory actions of BoNTs in reducing the transmission of itch are presented, and future potential directions are outlined. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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7 pages, 2561 KiB  
Review
Novel Anatomical Guidelines on Botulinum Neurotoxin Injection for Wrinkles in the Nose Region
by Kyu-Ho Yi, Ji-Hyun Lee, Hye-Won Hu and Hee-Jin Kim
Toxins 2022, 14(5), 342; https://doi.org/10.3390/toxins14050342 - 15 May 2022
Cited by 18 | Viewed by 13153
Abstract
Botulinum neurotoxin injection surrounding the nose area is frequently used in aesthetic settings. However, there is a shortage of thorough anatomical understanding that makes it difficult to treat wrinkles in the nose area. In this study, the anatomical aspects concerning the injection of [...] Read more.
Botulinum neurotoxin injection surrounding the nose area is frequently used in aesthetic settings. However, there is a shortage of thorough anatomical understanding that makes it difficult to treat wrinkles in the nose area. In this study, the anatomical aspects concerning the injection of botulinum neurotoxin into the nasalis, procerus, and levator labii superioris alaeque muscles are assessed. In addition, the present knowledge on localizing the botulinum neurotoxin injection point from a newer anatomy study is assessed. It was observed that, for the line-associated muscles in the nose region, the injection point may be more precisely defined. The optimal injection sites are the nasalis, procerus, and levator labii superioris alaeque muscles, and the injection technique is advised. We advise the best possible injection sites in association with anatomical standards for commonly injected muscles to increase efficiency in the nose region by removing the wrinkles. Similarly, these suggestions support a more precise procedure. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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21 pages, 8040 KiB  
Review
Multidimensional Effectiveness of Botulinum Toxin in Neuropathic Pain: A Systematic Review of Randomized Clinical Trials
by Lorenzo Lippi, Alessandro de Sire, Arianna Folli, Francesco D’Abrosca, Elisa Grana, Alessio Baricich, Stefano Carda and Marco Invernizzi
Toxins 2022, 14(5), 308; https://doi.org/10.3390/toxins14050308 - 27 Apr 2022
Cited by 20 | Viewed by 3334
Abstract
Although botulinum toxin (BoNT) has been suggested as a treatment to counter neuropathic pain, no previous systematic reviews investigated the multidimensional effects of BoNT on pain relief and Health-Related Quality of Life (HR-QoL). The aim of this systematic review is to summarize the [...] Read more.
Although botulinum toxin (BoNT) has been suggested as a treatment to counter neuropathic pain, no previous systematic reviews investigated the multidimensional effects of BoNT on pain relief and Health-Related Quality of Life (HR-QoL). The aim of this systematic review is to summarize the current evidence on the effectiveness of BoNT treatment for neuropathic pain, and to characterize its multidimensional effectiveness in order to guide physicians in clinical practice. Five databases were systematically searched up to 4 April 2022, to identify randomized controlled trials satisfying the following criteria: adults suffering from neuropathic pain, BoNT administration, any comparator, multidimensional assessment of pain as primary outcome, HR-QoL, physical function, anxiety and depression, and sleep quality as secondary outcomes. Twelve studies were included. The multidimensional pain scales used were short-form McGill Pain Questionnaire, Neuropathic pain scale, Neuropathic Pain Symptom Inventory, International SCI Pain Basic Data Set, West Haven-Yale Multidimensional Pain Inventory, Brief Pain Inventory, and Douleur Neuropathique 4. These scales highlighted the positive effects of BoNT administration. According to the Jadad scale, all the RCTs included were high-quality studies. BoNT administration might be effectively introduced in the comprehensive management of neuropathic pain. Further research should focus on optimal and cost-effective therapeutic protocols. Full article
(This article belongs to the Special Issue Botulinum Toxins: New Uses in the Treatment of Diseases)
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