Action Of Botulinum Toxin Research Articles

Neurotropic Effect of Botulinum Toxin and the Potential of Specific Serum Therapy in Botulism (Review)

INTRODUCTION. The outbreak of foodborne botulism that occurred in Russia in June 2024 once again demonstrated the danger of this rather rare but severe infectious disease caused by ingesting botulinum neurotoxin. The only aetiological treatment for botulism is currently the administration of antitoxins against various serotypes of botulinum toxin. However, antitoxins do not provide rapid regression of neurological symptoms, which may raise doubts about the effectiveness of the selected treatment option. It is impossible to assess the potential of specific treatment without understanding the mechanisms of action of botulinum toxin and antitoxin.AIM. This study aimed to systemise information on the mechanism underlying the damaging effect of botulinum neurotoxin, aetiological antitoxin treatment, and the patient recovery process.DISCUSSION. The mechanism underlying the damaging effect of botulinum neurotoxin consists in the destruction of SNARE proteins in presynaptic cholinergic nerve terminals, which disrupts the release of acetylcholine into the synaptic cleft and the transmission of excitation between neurons. The lack of acetylcholine at the neuromuscular junction results in a distinctive form of persistent flaccid paralysis. The specific mechanism of action of botulinum toxin determines the treatment strategy, which includes a set of life-sustaining measures and the earliest possible antiserum administration. If used within 48 hours from the onset of symptoms, botulinum antitoxin binds botulinum toxin circulating in the blood, which stops the progression of paralysis and prevents further disorders in patients. However, botulinum antitoxin cannot neutralise the effect of the toxin that has already bound to nerve receptors, so clinical symptoms may worsen within 12 hours after antiserum administration. Restoration of normal neuronal transmission occurs through the formation of new axonal sprouts and can take a long time.CONCLUSIONS. Antitoxin administration is effective and irreplaceable in the aetiological treatment of botulism. Nevertheless, the duration of recovery depends on the speed of reinnervation and restoration of transmission at the neuromuscular junction.

Using Neuromodulators to Improve Scar Formation, Keloids, Rosacea, and Antiaging.

Botulinum toxin A (BoNT-A) treatment has many uses in dermatology. Its mechanism of action and long-term effects for scar formation, rosacea, and antiaging are still being investigated. To conduct a literature review on BoNT-A to further investigate its use in scar formation, rosacea, and antiaging. A literature review was conducted using PubMed on botulinum toxin treatment for scar formation, rosacea, and antiaging. Studies discussing the toxin mechanism of action and treatment algorithm were included. The authors also provided their personal experience in BoNT-A use for these 3 conditions. The mechanism of action of Botulinum toxin A in improving scar formation, rosacea, and antiaging is now better understood. While it is effective in the short term, little is still known about how frequently treatment needs to be repeated and if there are any long-term effects. While in vitro studies have supporting evidence on the mechanism of action of BoNT-A on scar formation, rosacea, and antiaging, further studies are needed to identify long-term treatment effects.

Antiarrhythmic Potential of Epicardial Botulinum Toxin Injection for Suppression of Postoperative Atrial Fibrillation.

Following heart surgery, postoperative atrial fibrillation (AF) is the most prevalent kind of secondary AF and the most frequent adverse event. Postoperative AF is related to a number of unfavorable cardiac outcomes, such as heart failure, stroke, and death. However, the pharmacological treatment for postoperative AF is only relatively efficient and is frequently linked to detrimental complications, including symptomatic bradycardia with atrioventricular block due to rate control drugs and elevated hemorrhage hazard attributable to the administration of anticoagulants. Ablation procedures also result in the irreversible damage of cardiac anatomic structures, which may have long-term negative implications on heart performance. As a result, there is an unmet demand for treatments that can minimize the incidence of postoperative AF in an effective and safe manner. Botulinum toxin is an established neurotoxin that has progressively gained use in every medical science domain. It hinders the propagation of impulses across nerve fibers without causing immediate damage to the cardiac tissue. The transient feature of botulinum toxin action and the eventual restoration of the autonomic nervous system transmission are undeniably advantageous and may render botulinum toxin a potential and feasible treatment approach for postoperative AF.

How does botulinum toxin really work?

Over the past 30 years, Botulinum toxin (BoNT) has emerged as an effective and safe therapeutic tool for a number of neurological conditions, including dystonia. To date, the exact mechanism of action of BoNT in dystonia is not fully understood. Although it is well known that BoNT mainly acts on the neuromuscular junction, a growing body of evidence suggests that the therapeutic effect of BoNT in dystonia may also depend on its ability to modulate peripheral sensory feedback from muscle spindles. Animal models also suggest a retrograde and anterograde BoNT transportation from the site of injection to central nervous system structures. In humans, however, BoNT central effects seem to depend on the modulation of afferent input rather than on BoNT transportation. In this chapter, we aimed to report and discuss research evidence providing information on the possible mechanisms of action of BoNT in relation to treatment of dystonia.

Effect of Bladder Injection of OnabotulinumtoxinA on the Central Expression of Genes Associated with the Control of the Lower Urinary Tract: A Study in Normal Rats.

To investigate a possible central mechanism of action of Botulinum toxin A (BoNT/A) following injection in the bladder, complementary to the acknowledged peripheral bladder effect, we studied changes in the expression of neuropeptides and receptors involved in lower urinary tract function in the spinal cord (SC) and dorsal root ganglia (DRG) of normal rats following BoNT/A bladder injection. Thirty-six Sprague-Dawley rats, divided into three groups of n = 12, received bladder injections of 2U or 5U OnabotulinumtoxinA (BOTOX®), or saline. Six animals from each group were sacrificed on days 7 and 14. Expression of Tachykinin 1 (Tac1), capsaicin receptor (TRPV1), neuropeptide Y (NPY), proenkephalin (PENK) and muscarinic receptors M1, M2, M3, was evaluated in the bladder, L6-S1 DRG, and SC segments using real-time PCR and Western blotting. Real-time PCR revealed increased expression of NPY in all tissues except for SC, and increased TRPV1 and PENK expression in DRG and SC, whereas expression of Tac1, M1 and M2 was decreased. Less significant changes were noted in protein levels. These findings suggest that bladder injections of OnabotulinumtoxinA may be followed by changes in the expression of sensory, sympathetic and cholinergic bladder function regulators at the DRG/SC level.

Indomethacin-intolerant hemicrania continua: treatment with botulinum toxin

Hemicrania continua (HC) is responsive to indomethacin, which is useful both for acute treatment and for chronic suppressive therapy. However, this medication is poorly tolerated in many patients. The treatment of indomethacin-intolerant HC is poorly defined. We present a patient with HC who developed acute kidney injury on indomethacin and proved refractory to multiple other treatment modalities. She had an excellent response to botulinum toxin, with a duration of benefit similar to that reported previously in HC and in chronic migraine. Botulinum toxin may be a therapeutic option in patient with HC who do not tolerate indomethacin. The possible mechanisms of action of botulinum toxin in HC are discussed.

Feeding Intolerance in a 3-month-old.

Feeding Intolerance in a 3-month-old.

Onabotulinumtoxina reduce visual cortical excitability in chronic migraine: Preliminary results of a study with sound induced flash illusions

The number of sound-induced flash illusions (SIFI) perceived are related with the level of visual cortex (V1) excitability. In episodic migraineurs, in response to visual-acoustic illusions, V1 is hyperexcitable. The injection of botulinum toxin type A was approved as a therapy for chronic migraine (CM). Recent studies have correlated the action of botulinum toxin with the release of CGRP and cortical excitability. We used SIFI to evaluate the V1 excitability in CM at baseline and 3 months after treatment with botulinum toxin.

Botulinum Toxin in the Treatment of Vasopressor-associated Symmetric Peripheral Gangrene.

Summary:Symmetric peripheral gangrene (SPG) affects peripheral tissues of critically ill patients and can have severe disfiguring and debilitating effects. It can occur in the setting of multiple conditions, and it is associated with the use of vasopressors. There are no evidence-based treatments available for patients who develop SPG. Botulinum toxin has emerged as a potential therapy in vasospastic disorders, and we hypothesized that it may be used in the treatment of tissue ischemia in critically ill patients on vasopressors. We present a case of a patient who developed vasopressor-associated SPG and who experienced complete resolution after local injection with botulinum toxin. While the action of botulinum toxin on skeletal muscle is best understood, it has also been demonstrated to attenuate the release of multiple vasoconstrictive factors that impact vascular smooth muscle and modulate calcium and nitric oxide. These effects may result in vasodilation and improvement of cutaneous ischemia when injected locally. Clinicians may consider this local therapy in the treatment of vasopressor-associated symmetric peripheral gangrene.

Injection Site Pain, Onset and Duration of Action of Botulinum Toxin Reconstituted in Normal Saline With and Without Sodium Bicarbonate: A Prospective, Single Center, Randomized, Double-Blind Interventional Study.

Purpose: This study was designed to investigate the effects of botulinum toxin type A injections diluted with the mixture of sodium bicarbonate and normal saline on pain reduction, onset of action, and duration of action. Methods: This is a prospective, randomized, double-blind clinical study, which included 30 female patients (age >25). The patients were randomized to receive botulinum toxin injections diluted with normal saline and sodium bicarbonate on one side of the face and saline control injections on the other side. Pain severity was assessed using visual analogue scale. The onset and duration of action were recorded according to the patients' subjective opinions after 1 week and 3 months, respectively. Results: Lower pain intensity ratings were observed when botulinum toxin was diluted with 0.05 and 0.1 mL of sodium bicarbonate as compared to saline. Regarding the onset of action, the botulinum toxin injections diluted with saline and 0.1-mL sodium bicarbonate side showed faster response in many patients than other dilutions (P < .001). Both the 0.05-mL and 0.1-mL sodium bicarbonate concentrations showed longer duration effects on patients than other concentrations. Conclusion: The use of sodium bicarbonate and saline in a mixture for the dilution of botulinum toxin can decrease patients' discomfort and provide a faster action with longer duration effects.

The Anti-Nociceptive/Anti-Inflammatory Actions of Botulinum Toxin A for the Treatment of Chronic Pain: A Literature Review

The Anti-Nociceptive/Anti-Inflammatory Actions of Botulinum Toxin A for the Treatment of Chronic Pain: A Literature Review

Botulinum toxin in low urinary tract disorders - over 30 years of practice (Review).

Botulinum toxin is a substance produced by Clostridium Botulinum and is responsible for human botulism. This substance is a poison, a neurotoxin, but used in limited quantities it can be a cure for some diseases. It is well connected to a large variety of medical applications. The mechanism of action relies on blocking the acetylcholine at the neuromuscular junction, which blocks the transmission of the nervous impulse with secondary flaccid paralysis. In urology, its role in idiopathic overactive bladder and neurogenic bladder is well known. We performed a thorough review using PubMed and other databases, revising the mechanisms of botulinum toxin action in urologic pathology, treatment procedures and other options. Botulinum toxin is a well-studied substance with a large number of applications in medicine. In urologic pathology, overactive bladder and neurogenic bladder are backed by robust studies that support the therapeutic role of this substance. The toxin has multiple effects, such as inhibition of the nerve growth factor, blocking the bladder sensory afferent pathway and apoptotic effect on the prostate tissue, by inhibiting the substance P, altering the nociceptive pathways. Interstitial cystitis and other rare pathologies show promising results, but further studies are needed. The role of botulinum toxin in benign prostatic hyperplasia is still not elucidated.

Mechanism of Action of Botulinum Toxin A in Treatment of Functional Urological Disorders

Intravesical botulinum toxin (BoNT) injection is effective in reducing urgency and urinary incontinence. It temporarily inhibits the detrusor muscle contraction by blocking the release of acetylcholine (Ach) from the preganglionic and postganglionic nerves in the efferent nerves. BoNT-A also blocks ATP release from purinergic efferent nerves in the detrusor muscle. In afferent nerves, BoNT-A injection markedly reduces the urothelial ATP release and increases nitric oxide (NO) release from the urothelium. BoNT-A injection in the urethra or bladder has been developed in the past few decades as the treatment method for detrusor sphincter dyssyndergia, incontinence due to neurogenic or idiopathic detrusor overactivity, sensory disorders, including bladder hypersensitivity, overactive bladder, and interstitial cystitis/chronic pelvic pain syndrome. Although the FDA only approved BoNT-A injection treatment for neurogenic detrusor overactivity and for refractory overactive bladder, emerging clinical trials have demonstrated the benefits of BoNT-A treatment in functional urological disorders. Cautious selection of patients and urodynamic evaluation for confirmation of diagnosis are crucial to maximize the successful outcomes of BoNT-A treatment.

Femtosecond sub-Bowmen keratomileusis at the peak of the action of Botulinum toxin A, introduced into extraocular muscles in a patient with nystagmus: A clinical case

A clinical case of excimer laser correction performed by sub-Bowman femtosecond keratomileusis at the peak of botulinum toxin A effect in a patient with high congenital anisometropic myopia and horizontal nystagmus is presented. Keratorefractive surgery improved functional visual performance and the parameters of nystagmus.

Qualitative and quantitative scintigraphy in sialorrhea before and after botulinum toxin injection

Sialorrhea is excessive saliva production and its usual escape of from the oral cavity. The use of botulinum toxin has been preconized, but its effectiveness until now has been unreliably measured. Our objective was to qualitatively and quantitatively determine the effectiveness of botulinum toxin injection in the reduction of saliva production by the parotid gland. Outcomes research. Patients with moderate-to-critical sialorrhea had one of the parotid glands injected with 50 U of botulinum toxin, leaving the other as the control. Fifteen days after the toxin injection, they underwent scintigraphic analyses with intravenous injection of 10 mCi (37 MBq) of Tc-99 m (sodium pertechnetate). After this, the noninjected gland was treated for therapeutic complementation. The glands injected with botulinum toxin showed uptake reduction in 100% of patients. The uptake reduction in counts per second varied from 8% to 36%. The Wilcoxon paired test comparing the control glands with those injected showed a significant difference for the action of botulinum toxin (P = .0039). The scintigraphic study of parotid glands shows that botulinum toxin is effective in reducing sodium pertechnetate uptake. 2c Laryngoscope, 129:2521-2526, 2019.

Use of Botulinum Toxin in Ophthalmology.

Botulinum toxin is an important treatment for many conditions in ophthalmology, including strabismus, nystagmus, blepharospasm, hemifacial spasm, spastic and congenital entropion, corneal exposure, and persistent epithelial defects. The mechanism of action of botulinum toxin for both strabismus and nystagmus is the neuromuscular blockade and transient paralysis of extraocular muscles, but when botulinum toxin is used for some forms of strabismus, a single injection can convey indefinite benefits. There are two unique mechanisms of action that account for the long-term effect on ocular alignment: (1) the disruption of a balanced system of agonist-antagonist extraocular muscles and (2) the reestablishment of central control of alignment by the binocular visual system. For other ocular conditions, botulinum toxin acts through transient paralysis of periocular muscles. Botulinum toxin is a powerful tool in ophthalmology, achieving its therapeutic effects by direct neuromuscular blockade of extraocular and periocular muscles and by unique mechanisms related to the underlying structure and function of the visual system.

Objective assessment of cortical activity changes in stroke patients before and after hand rehabilitation with and without botulinum toxin injection

BackgroundUpper limb spasticity is a disabling condition and may result in severe functional limitation. The peripheral action of botulinum toxin (BTX) injection on spasticity is well known, but there are debates around its possible central action.AimThe aim of this study was to assess the clinical, functional, and cortical activation outcome of two antispastic treatments for stroke of the hand and wrist. Thirty patients with upper limb poststroke spasticity were recruited in this study.Patients and methodsThey were randomly allocated to two groups: group A and group B. Both groups received rehabilitation program, whereas group B received additional BTX injection. All patients were assessed at baseline and 8 weeks after treatment using the Modified Ashworth Scale, the Action Research Arm Test and Nine-Hole Peg Test, and somatosensory-evoked potential study of the median nerve.ResultsGroup B showed a higher percentage of change in Modified Ashworth Scale of the wrist flexors and long flexors of fingers and in Action Research Arm Test compared with group A.ConclusionBTX injection in spastic muscles of the wrist and hand, followed by a rehabilitation program led to greater clinical and functional improvement compared with implementing the rehabilitation program alone.

The potential of resting-state functional magnetic resonance imaging for studying the pathophysiology of primary focal dystonia

Abstract Resting-state functional magnetic resonance imaging (R-fMRI) assesses the state of low-frequency fluctuations of the BOLD-signal showing spontaneous neuronal activity in different areas of the brain. Hence, R-fMRI allows one to visualize the synchronicity of generation of certain neurophysiological phenomena in different regions of the central nervous system, including the ones being remote from one another, by linking them into a functional network and assessing brain connectivity in normal state and in pathology. This technique has proved itself in the study of neurodegenerative diseases. In this review, we present the results of using R-fMRI for the most common forms of primary focal dystonia (blepharospasm and cervical dystonia) compared to the data of task-based fMRI and some other neuroimaging technologies such as positron emission tomography and voxel-based morphometry. It has been demonstrated in many studies that R-fMRI allows to assess disturbances in cerebral architecture and complex rearrangements in the neural network in patients with focal dystonia, including those after administration of botulinum toxin. This makes it possible to study more thoroughly the pathophysiological foundations of focal dystonia and the variety of mechanisms of botulinum toxin therapy in patients with these pathologies, including the central (indirect) mechanisms of action of botulinum toxin.

Action mechanisms of Onabotulinum toxin-A: hints for selection of eligible patients.

In the past few decades, the so-feared botulinum toxin has conversely acquired the role of a ever more versatile therapeutic substance, used in an increasing number of pathological situations, including chronic headache and more precisely in the prophylaxis of chronic migraine. The medical use of botulinum toxin allowed to better understand its multiple mechanisms of action. Investigations about the pathophysiology of primary and secondary headaches has shown a series of common biological elements that frequently are also targets of the action of botulinum toxin. These increasing evidences allowed to identify some biochemical, neurophysiological and radiological markers that may be useful in the individuation of patients which probably will respond to the treatment with Onabotulinum toxin-A among chronic migraineurs. These predictors include CGRP plasmatic levels, specific laser-evoked potential responses, peculiar brain MRI and fMRI and characteristic clinical manifestations. Unfortunately, at now, these predictors are still not available for the clinical practice. Furthermore, the better knowledge about biology of headaches and regarding botulinum toxin activities may also help in directing investigations on the possible use of Onabotulinum toxin-A in other headaches different from migraine. This review tries to show in detail these biological mechanisms and their implication in selecting patients eligible for the treatment with Onabotulinum toxin-A.

Histological and immunohistochemical findings of the action of botulinum toxin in salivary gland: systematic review.

The treatment of sialorrhea is necessary for the constant risks posed by hypersalivation. A new therapeutic option comes up with the application of botulinum toxin in salivary glands. However, little is known about its mechanism of action in glandular tissue. Based on the above, this work had the objective to systematically review the literature about the action of botulinum toxin on submandibular and parotid salivary glands tissues. Electronic search was performed in databases of great relevance for this study (PubMed, SciELO, HighWire, Crossref, Scopus, Science Direct, MEDLINE, OLDMEDLINE, Serials Database, NLM Catalog, LILACS and IBECS). Inclusion and exclusion criteria for articles were established, and a total number of 14 articles were selected and used. There are few publications that clarify how the salivary gland acini behave with application of botulinum toxin. Although, the immunohistochemical findings were consistent among authors, showing weak immunoreactivity in glands treated with botulinum toxin. Histometric data are divergent, requiring more detailed studies to answer the questions about the efficacy and safety of botulinum toxin in salivary glands.