Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine
Abstract
:1. Introduction
2. Clinical Conditions in Which the Acetylcholine Mechanism Is Targeted with BT-A
2.1. Dermatological Use
2.2. Dystonias
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- Cervical Dystonia: Cervical dystonia is a focal dystonia characterized by repetitive and involuntary contractions in the shoulder and neck muscles, accompanied by abnormal posture in the head, neck, and shoulders [32]. Patients’ complaints of tremor, pain, and disability negatively affect their quality of life, both functionally and psychologically. Pharmacological drugs are included in the treatment. Although it is stated that the healing effectiveness of physiotherapy and rehabilitation treatment increases when applied with BT-A and that cognitive behavioral therapies can also be recommended, the evidence strength is insufficient [33,34]. Surgical procedures can be performed when necessary in cases such as degenerative changes in the spine, myeloradiculopathy, or atlantoaxial instability [35]. In light of the literature, the first preferred method in the treatment of cervical dystonia is local BT-A application. BT-A acts by inhibiting the release of acetylcholine at the neuromuscular junction, blocking neuromuscular transmission. BT-A can be applied to the sternocleideomastoid, splenius capitis, levator scapula, semispinalis, trapezius, and scalene muscles, and depending on the clinical condition of the patient, the application of BT-A may involve several muscles or all the muscles just mentioned. The treatment effect starts within a week, and the duration of the effect can last up to 6 months [32]. Applications are made at at least 3-month intervals, keeping in mind that antibody formation occurs. Recommended doses may vary depending on the patient and the muscles to be applied; the range of doses for the injection can be a range of 198/200 to 360 units [36,37]. Evidence level A has been reported for BT-A in improving cervical dystonia, level A has been reported for reducing pain intensity, and level B has been reported for improving quality of life [38,39].
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- Blepharospasm: Blepharospasm is a dystonia that occurs with spasms of the orbicularis oculi muscles, causing involuntary closure of the eyelid [40]. Periocular muscles may also be affected. Increased blinking and difficulty in involuntary eyelid closing and opening generally affect both eyes symmetrically. This difficulty in opening and closing the eyes may affect patients’ ability to perform their daily activities, and patients may have difficulty performing their duties during the day [40]. BT-A applied to the affected eye contour muscles reduces muscle contraction by blocking presynaptic acetylcholine release at the neuromuscular junction [41].
2.3. Neurological Diseases Accompanied by Spasticity
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- Cerebral Palsy in Children: Cerebral palsy is a disease characterized by brain damage occurring in the early stages of development, where pyramidal, extrapyramidal dysfunction, and apraxic problems occur together [42]. In extrapyramidal dysfunctions, spasticity, dystonia, rigidity, spasm, or chorea findings may be observed. As the child grows, it is also possible to experience consequences such as contractures, joint problems, or growth retardation [42]. After the diagnosis is made in the treatment of cerebral palsy, physiotherapy and rehabilitation treatment take place throughout the process with the participation of the child and their family [43]. Considering growth and muscle joint development, BT-A application is also widely used in treatment to improve hyperactivity, especially in the lower extremity muscles [43,44]. The toxin blocks the release of acetylcholine at the neuromuscular junction, causing flaccid paralysis [43]. The effects of the BT-A application last for 3-6 months [45]. However, considering the child’s growth and development, good clinical observation is required so that the muscle relaxation effect of BT-A can proceed healthily with the child’s normal development [45]. With BT-A application, reduction in pain and spasticity [46,47], increase in gross motor function and joint range of motion, improvement in gait pattern, and increase in quality of life in children with cerebral palsy have been shown in literature studies for periods ranging from 12 weeks to 2 years [43,48,49]. Although the reported side effects such as pain, weakness, and fatigue after the application are mild, it is stated that recommending BT-A application together with physiotherapy, rehabilitation treatment, and orthoses can minimize possible surgical operations in the future [43].
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- Upper Motor Neuron Diseases in Adults: Spasticity, which is combated in upper motor neuron lesion diseases such as multiple sclerosis, stroke, spinal cord injuries, and traumatic brain injuries, is among the most important causes of disability in adults. Again, problems such as joint deformities, contractures, and pain caused by spasticity affect the quality of life, emphasizing the need for the treatment process to be handled correctly [50]. BT-A has a level of evidence of A for focal spasticity in the upper and lower extremities [46,47,51]. BT-A, which has reversible effects, provides positive effects on individuals by improving walking patterns and mobility, increasing joint range of motion, reducing pain, and increasing the quality of life in daily living activities [52,53,54,55,56]. For example, spasticity, which is seen in almost 80% of patients with multiple sclerosis, may vary depending on the attack. In spinal cord injuries, spasticity is observed in the majority of patients until the first year after the injury. In traumatic brain injury, spasticity can develop very rapidly in the acute phase [50]. It is stated that BT-A treatment applied after the necessary evaluations in these diseases shows effects for 3–6 months, and the effectiveness of rehabilitation treatments may increase with the decrease in pain and spasticity [50]. In order to increase the duration of the effectiveness of BT-A and reduce the interruption of treatment, the time between injections should be carefully evaluated and not kept long [56]. Therefore, it is emphasized that BT-A treatment is a good aid because it is an important part of multimodal treatment for these diseases [50].
2.4. Essential Head Tremor
2.5. Urological Problems
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- Incontinence and Related Problems: In cases of involuntary contraction or insufficient relaxation of the sphincter in urological disorders, BT-A is used by targeting the inhibitory mechanism of acetylcholine release at the neuromuscular junction in the striated muscle [59,60,61]. Normalization of continence, an increase in cystometric bladder capacity, an increase in maximum urine flow rate, a decrease in urinary incontinence, catheterization, improvements in mean detrusor pressure, and quality of life are achieved. In addition, these effects can last up to almost 12 months with repeated injections [62,63,64,65].
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- Ejaculation Problems: BT-A is among the treatment methods for premature ejaculation problems. BT-A aims to inhibit the rhythmic contraction of the bullospongiosus and ischiocavernosus muscles by blocking presynaptic neuron activity and reducing norepinephrine flow [66]. It is aimed at increasing nitric oxide formation by blocking the release of acetylcholine from cholinergic neurons [67]. As a result, normal erection is achieved by relaxing the bullospongiosus and ischiocavernosus muscles [67]. Literature studies report that patients do not have prolonged intravaginal ejaculatory delay times or complications after BT-A application. In addition, the long duration of action and ease of application are stated as advantages of BT-A [68,69].
2.6. Strabismus
2.7. Hyperhidrosis and Acral Peeling Skin Syndrome
2.8. Temporomandibular Joint Disorders
2.9. Obesity
3. Clinical Conditions in Which the Acetylcholine Mechanism, CGRP, Glutamate, and Substance P Are Targeted by BT-A
3.1. Chronic Migraine
3.2. Cancer
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- Cancer pain after radiation and after surgery: Two types of pain may affect cancer patients: neuropathic pain due to lesions or after surgery, and local muscle spasms, especially after radiotherapy [102]. The analgesic effect occurs through two different mechanisms. Inhibition of acetylcholine release at the neuromuscular junction is mainly responsible for relieving pain caused by muscle spasms. In the case of neuropathic pain, the analgesic effect is mainly due to the inhibition of pain neurotransmitters in the peripheral and central sensory systems [103,104,105]. In the studies, the duration of effect of BT-A injections to relieve pain was 3–6 months [106].
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- Repair and healing of parotid glands damaged by cancer, radiation, or surgery: Botulinum toxin injection was used for the treatment of parotid gland damage such as gustatory hyperhidrosis (GH), sialorrhea, fistula, and sialocele formation, a safe and effective way to control sialorrhea and to heal the fistula [107,108]. Anecdotal observations have shown that 3 to 7 years of treatment are safe [107]. Further studies are needed to confirm these results, and long-term safety should be investigated in controlled, prospective clinical studies.
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4. Clinical Conditions in Which CGRP, Glutamate, and Substance P Are Targeted by BT-A
4.1. Trigeminal Neuralgia
4.2. Neuropathic Pain
4.3. Myofascial Pain Syndrome
5. Other Mechanisms
Hair Loss
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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Botulinum Toxin | FDA-Approved Indications |
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OnabotulinumtoxinA |
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Onan, D.; Farham, F.; Martelletti, P. Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine. Toxins 2024, 16, 309. https://doi.org/10.3390/toxins16070309
Onan D, Farham F, Martelletti P. Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine. Toxins. 2024; 16(7):309. https://doi.org/10.3390/toxins16070309
Chicago/Turabian StyleOnan, Dilara, Fatemeh Farham, and Paolo Martelletti. 2024. "Clinical Conditions Targeted by OnabotulinumtoxinA in Different Ways in Medicine" Toxins 16, no. 7: 309. https://doi.org/10.3390/toxins16070309