Role of Botulinum Toxin Type A in Migraine Volume 50- Issue 3

Sharjeel Chaudhry^1*, Zarmina Ehtesham² and Usman Asif¹

• ¹Dow International Dental College, Karachi, Pakistan
• ²Hamdard University, Pakistan

Received: May 02, 2023;   Published: May 15, 2023

*Corresponding author: Sharjeel Chaudhry, Dow International Dental College, Karachi, Pakistan

DOI: 10.26717/BJSTR.2023.50.007947

Abstract PDF

This article focuses on the usage of Botox type A (BoNT-A) as a treatment for migraines in patients. Almost 10% of the global population suffers from migraines, with middle-aged and young women being the most prevalent users of BoNT-A. BoNT-A functions by blocking acetylcholine release, preventing neuro exocytosis, and causing selective nerve terminal targeting. It has been utilised to treat a variety of medical conditions, including focal dystonias, spasticity, muscle spasms, achalasia, and blepharospasm. The article examines the evidence-based clinical criteria with healthcare research and policies to establish the efficacy of BoNT-A in treating and preventing migraines caused by botulinum toxin. The results of the study indicate that BoNT-A injections limit muscle contractions and function as a barrier to prevent neurotransmitters from transferring pain signals to the brain, resulting in a reduction in migraine pain. The effects are temporary, and patients must undergo treatment every 12 weeks. Several studies have demonstrated that long-term treatment with onabotulinumtoxinA is safe and very successful in preventing migraine headaches; after three sessions of therapy, at least 65% of patients exhibited a 50% mean headache reduction every month. In addition, patients who got Botulinum toxin type A treatment for migraines had maintained effectiveness and a reduction in the number of days per month with an intensity of more than four. Overall, the article gives insights into the theoretical goal and use of BoNT-A in lowering migraine severity, as well as an analysis of clinical evidence that is consistent with the treatment strategy for patients.

Keywords: Headache; Migraine; Botox; Scalp Injections

Most individuals use Botox because it reduces facial wrinkles and is recognised as a therapy for migraine patients. Middle-aged and young women are the most common users. Nearly 10% of people worldwide suffer from migraine symptoms, which are common among women [1]. Additionally, because of the severe pain it causes, it has a tremendous negative impact on the individual. However, BoNT-A offers a technique to lessen the severity of migraines, and studies show that people with migraines who receive BoNT-A treatments always have 50% fewer migraine days. Botulinum toxin has in recent times led to exciting research programs and excitement in the management of various disorders associated with the spasm of skeletal and smooth muscles. Botox works by inhibiting the release of acetylcholine in the presynaptic cholinergic joint. When proteolytic activity happens on the intracellular proteins that enhance synaptic vesicle fusion with the plasma membrane, Neuroexocytosis can be prevented using Botox [2]. An extremely effective, long-lasting, and precise inhibitor of acetylcholine release, Botox type A (BoNT-A) induces selective targeting to nerve terminals by the enhanced affinity that facilitates binding to ecto-receptors present inside the motor nerve endings. BoNT-A has continuously been used in the past few decades to treat different health problems: focal dystonias, spasticity, muscle spasms, achalasia, and blepharospasm. The reduction of severity when experiencing a clinical issue such as Migraine has led to increased research on the independent antinociceptive impact of BoNT-A, and pain is reduced or controlled before decreased muscle contractions in a Migraine patient [3].

With Enzymatic neurotransmitter release blockade, it is said to vital as it holds direct clinical antinociceptive impacts of BoNT-A. Consequently, BoNT-A exposure helps prevent Fos’ expression, which is a product of neuronal stimuli and an individual’s early genes (C-fos) and blocks the release of glutamate. To control and prevent migraines caused by botulinum toxin, the modulations of peripheral sensitization and central sensitization are thought to be extremely effective treatments. It includes using evidence-based clinical criteria with healthcare research and policies that have previously been used towards jaw muscle pains. Still, the study lacked any outcome of pain relief across all tests (Table 1). This study seems weird to involve BoNT-A research comparisons between Migraine patients and regular individual volunteers; however, it does not seem to represent any Migraine experimental models. The research on ordinary people enhances assessing putative actions of Botulinum toxin type A with the absence of severe muscle spasms [4]. The context aims to determine if Botox type A (BoNT-A) injections are essential in treating migraines in patients. To examine the theoretical purpose and the use of BoNT-A in a reduction of Migraine severity and analysis of clinical evidence that aligns with the therapeutic strategy toward patients.

Table 1: Efficacy of Botulinum Toxin Type A in Migraine after Three Courses.

Botulinum toxin type A helps prevent migraine headaches by providing a barrier to avoid neurotransmitters from transmitting pain signals to the brain and reducing muscle contractions. This is essential in reducing the severe pain generated by Migraine, enabling patients to live an everyday life for an extended period without experiencing any Migraine discomforts [5]. However, Botulinum toxin type A effects are not permanent, and the patients are required to receive treatment from time to time, like getting Botulinum toxin type A spasm injections after every 12 weeks. After a few weeks, the infusion is effective to experience some relief, and doctors may adjust the timeline according to individual patient needs. The following results were results from various studies on Botulinum toxin type A and Migraine: There is an expected 65% response rate in Migraine patients treated with Botulinum toxin type A after three courses. At the same time, another study shows that treatment with onabotulinumtoxinA for a long duration is safe and highly effective in preventing migraine headaches. A study that demonstrates a short-period efficacy of the treatment is given after every three months (Bonafede et al., 2018). It involved the assessment of patients with significant responses after three sessions of therapy. The results indicated that when headache intensity increased, the number of headaches per day or month decreased significantly. Additionally, there was a monthly reduction in the number of head pain drugs prescribed to acute patients (Table 2). At least 65 patients indicated a 50% mean headache reduction every month after experiencing three sessions of therapy with a crucial follow- up of three years of treatment. Most of the Migraine patients (at least 86.1%) stayed for the entire study period [6].

Table 2: Sustained Efficacy of Botulinum Toxin Type A in Migraine.

However, a total of 9 patients left before the study period came to an end; because they felt the therapy was already effective with massive improvements at the time and thought they felt no need for further sessions. The study to understand the sustained efficacy of Botulinum toxin type A treatment for onabotulinumtoxinA; where researchers analyzed various changes in patients from trimester which involves the periods between 10 to 12 months (T1), two years ranging between 25 to 27 months (T2), and three years of between 37 to 39 months (T3) of treatment [5]. The study indicated that between T1 and T3, the mean of patient headaches per day decreased immensely, marking a 7.2 and 3.4, respectively. Also, the number of days each month with an intensity of more than four reduced significantly, showing 3.4 and 2.5 outcomes, respectively. The reduction leads to vital changes in the headache medication days each month from 4.7 to 2.8 at the end of the third period. Consequently, the crucial changes in all variables between timeframe T2 to T3 also led to significant improvements in Migraine patients, which enhanced the efficient efficacy of Botulinum toxin type A in long-term therapy. According to the researchers, all patients responded positively to therapy without any form of resistance, and all procedures adhered to more effective study without any crucial side effects. However, they further indicated that few patients went through mild and passing issues, such as neck and shoulder pain.

The immediate use of BoNT-A for Migraine treatment was accidental. There exists a correlation between intramuscular injections of BoNT-A and its relief of the severity of Migraine symptoms in its patients. Botulinum toxin type A is made from Botulinum toxin. Many people were scared of being injected with poison because they believed it to be dangerous for their health, but it contains minimal toxin contents [7]. Therefore, it has a few side effects on patients. Since 2010 onabotulinumtoxinA has been recognized as safe for Migraine treatment and should be administered by licensed doctors. According to various clinical reviews and studies, scalp injections to patients may help prevent migraine headaches for almost three months. This article addresses the use of Botulinum Toxin A (BoNT-A), sometimes known as Botulinum toxin type A, in the treatment of migraines. Migraine is a common condition that affects almost 10% of the world’s population, and it is more common in females. BoNT-A inhibits the release of acetylcholine in the presynaptic cholinergic junction, resulting in a decrease in muscular contractions and migraine intensity. The article examines the antinociceptive effects of BoNT-A, as well as its capacity to suppress the expression of Fos and block the release of glutamate. According to the study findings, there is a predicted 65% response rate in migraine patients treated with BoNT-A after three sessions of treatment [1]. Additionally, long-term treatment with onabotulinumtoxinA is safe and extremely effective in avoiding migraine headaches. Unfortunately, Botulinum toxin type A’s effects are not permanent, and patients must have treatment every 12 weeks to retain the advantages. The article emphasises the necessity for evidence- based clinical criteria and healthcare research to enhance the therapy strategy for migraine patients.

For over 30 years, doctors have continued to observe analgesic impacts of BoNT-A among patients with Torticollis spasmodic, which was focused mainly on muscle relaxation of Botox. The first evidence of the use fullness of Botulinum toxin type A for Migraine treatment was evident as many young women continued to get cosmetic Botox; it effectively blocked muscle contractions and nerve signals, improving the appearance of wrinkles between eyebrows and around the eyes. It is also used to delay the formation of lines that prevents the contraction of facial muscles. Thereby, as women continued to get BoNT-A for facial appearance reasons, doctors noticed that it helped relieve the severity of Migraine and their symptoms, and they began to use it as an immediate treatment for Migraine. They were using a non-random study that involved a total number of 106 patients; 77 patients were diagnosed with Migraine, and they began to get prophylactic treat with BoNT-A [8]. The benefits from the therapy were compiled and measured by patient-based reports, and 51% of the Migraine patients had complete responses, whereas 28% reported partial responses. The first inert treatment was in a double-blind study on migraine patients, carried out in 2000 and involved 123 patients. Here, patients were randomly divided into three groups where they were treated with a placebo of 75 or 25 mouse units of Botulinum toxin type A. There were no differences identified in participants treated with 75 mouse unit placebo group; however, treatment with 25 mouse units developed superiority to placebo with a high reduction of monthly Migraine attacks on patients.

Consequently, in the following periods, various clinical studies were conducted but did not indicate any positive impacts on tension headaches and episodic Migraine. And there were inconsistent results from clinical trials under controlled conditions in a multicentre study conducted among 702 chronic daily headaches patients who received a three-cycle treatment using 75,175 and 225 mouse units of Botulinum toxin type A and placebo for nine months [2]. There was a vital response from the group but lacked superiority to placebo. When Botulinum toxin type A was used for inert treatments on 58 patients experiencing chronic headaches each day, it tended to effectively reduce the severity of the headaches in 12 weeks after injection but lacked statistical efficiency. Multicentre research involved 279 patients with daily chronic headaches; after using three injection cycles for patients, there was an indication that prevention of the headaches remains effective for 30 days. However, the differences between verum and placebo groups did not indicate statistically relevant results. A subgroup study among 228 patients was conducted without the use of prophylactic medication at enrolment that demonstrated a statistically significant difference in the number of headaches after 30 days. Therefore, the authors of the study stated that Botulinum toxin type A is highly effective in treating Migraine patients without having been involved with other medications against the disease. In 2007, a small placebo-controlled and double-blinded study that involved 32 patients was a failure because it did not show any Botulinum toxin type A benefits as an effective treatment for migraines. However, in a further study where 86 patients were treated without overusing the medication, the results indicated a statistical significance where the use of Botulinum toxin type A helped to reduce the number of Migraine headaches [3].

Also, the Italian double-blind study involving 68 Migraine patients did not indicate any differences between placebo and onabotulinumtoxinA in reducing the number of headache days. Still, it showed that using Botulinum toxin type A helps reduce the consumption of pain medications among Migraine patients. A multicentre, open-label study provides further clinical information on the benefits and risks associated with the effects of Botulinum toxin type A injections on Migraine patients, which helps prevent Migraine headaches in patients for over one year. This study involved patients aged 18 to 73 years who were diagnosed with Migraine, and they received 155 units of Botox type A in 31 different fixed-sites; and a fixed injection across seven neck and head muscle patients [4]. The treatment was delivered every 12 weeks with additional or fewer than seven days on 108 weeks or nine treatment cycles. An early level 1B study on BoNT-A treatment therapy for Migraine patients indicates that the extent of effects did not offer convincing evidence and was involved with low order statistical significance. The patients that used to receive increased BoNT-A doses failed to show any positive changes, thereby enhancing insufficient evidence, which was not satisfying the question of the study. With the absence of a crucial response towards the treatment, the investigator suggested an emphasis on the granted permission of patients to use preventive medications. Still, the results were not directly related to the use of preventative medicines. The responses came in two phases from one time to another, whereby the characteristics were viewed more critically of which would have interfered with blinding during the trials.

The purpose of this article is to investigate the effectiveness of Botox type A (BoNT-A) injections in treating migraines in patients. The technique employed in this study involves a review of past studies and research on the use of BoNT-A injections in migraine treatment. The research technique employed in this article comprises a systematic review of several studies conducted on the usage of BoNT-A injections to treat migraines. The studies were examined to assess the effectiveness of BoNT-A injections in lowering migraine frequency, duration, and intensity. The research was conducted by evaluating different scientific databases, including PubMed, Google Scholar, and Cochrane Library, to locate relevant studies. The trials were selected based on the inclusion criteria, which included clinical trials, observational studies, and randomised controlled injections conducted to treat migraines using BoNT-A injections. Only studies with high-quality evidence were included in the review, which were selected based on their relevance and quality [4]. The studies included in the review were examined, and data were gathered, including the number of patients, duration of treatment, dose of BoNT-A injections, frequency of injections, and treatment effectiveness. The methodological quality and risk of bias of the studies were evaluated using the Cochrane Collaboration’s technique for assessing the risk of bias. In the article’s findings section, the results of the studies were summarised and examined.

The results section highlights the findings of the studies, including the response rate in patients treated with BoNT-A injections, the reduction in migraine frequency, duration, and severity, and the longterm effectiveness of BoNT-A treatment. This study examines the clinical data that supports the use of BoNT-A injections to treat migraines. The results of the study indicate that BoNT-A injections are beneficial in lowering migraine frequency, duration, and severity, and that their efficacy is sustained over a lengthy period of time [9]. The findings of this study have significant implications for the treatment of migraines and imply that BoNT-A injections may be a viable treatment option for migraine patients.

A double-blind, random, and placebo-controlled study is conducted among 16 regular human volunteers. Neuroselective sensory tests on current pain and thermal sensory tests for heat pain baseline within periods of 3, 14, and 28 days after injections indicated no differences between saline and onabotulinumtoxinA injected. Also, the flare locations did not show any differences. There were also no direct peripheral effects of onabotulinumtoxinA developed in level 1B studies that involved 65 volunteers. Therefore, from the three controlled trials, it’s evident that the direct impacts of BoNT-A in humans are ranked at level 1A. Demonstrating cutaneous allodynia among Migraine patients has helped generate the idea that the severe pain from Migraine is divided through central and peripheral neuronal sensitization. The study excludes the purpose of Botulinum toxin type A in interfering with allodynia for normal human beings, considering the reduction in the release of peripheral Neuropeptide. Also, it acknowledges that Botulinum toxin type A does not enhance any barriers between blood flows to the brain [4]. The use of low doses to patients during trials does not reach the trigeminal sensory fibres that surround the large Dural or cerebral vessels after the BoNT-A scalp injections to Migraine patients. However, the blood-brain barriers are not affected by severe Migraine attacks; having an aura or not, there remains a possibility of antidromic or proximal axoplasmic transfer of onabotulinumtoxinA along the trigeminal nerve fibres significant considerations during the study.

A study of females diagnosed with chronic moderate, where one experiences lots of jaw muscle pains, did not find any pain relief following trials using Botulinum toxin type A for treatment. In the beginning, it might seem unrealistic to compare BoNT-A studies by involving regular human volunteers and Migraine patients. Still, it does not appear to be an effective representative experimental model for Migraine. The survey among normal humans opens up a new assessment for the putative analgesic action of onabotulinumtoxinA in the absence of severe muscle pain. The primary purpose of the study using BoNT-A for Migraine prevention due to the theoretical belief that Botulinum toxin type A plays an essential role by enhancing independent, direct, and prolonged actions that do not have any relation to sudden muscle contractions; but the study is not appreciated by the clinical studies of regular human volunteers.

During the Migraine treatment, about 25% of the patients discover the temporary depression of muscles which is evident through their visible reactions after a BoNT-A injection followed by other side effects that prevent the effectiveness of understanding between BoNT-A patients and researchers and placebo. The immediate studies on Botulinum toxin type A injections for migraine headaches involved various doses, injection sites, and concentrations of BoNT-A [2]. The PREEMPT group came up with an injection pattern based on several studies of data collected from patients with tension headaches and Migraine. The research developed from the research involved two distinct approaches for injections of Botulinum toxin type A for Migraine; follow the pain and fixed injection sites. There are 50 mouse units of onabotulinumtoxinA that are diluted using 2 millilitres of saline, and each of the intramuscular sites is injected with five mouse units of Botox type A. The extension of studies on headache management and outcomes of BoNT-A used for muscular pain treatments other than preventing chronic tension-type headaches or Migraine seems irrelevant [3]. The evidence on the success of BoNT-A for use in avoiding Migraine generates suggestions about the placebo effects of new treatment procedures rather than dramatic experiments.

There is a need for therapists and Migraine patients to believe in this fact because each therapeutic process involves placebo effects. Also, in a study that involves multicentre trials, the enrolment of massive numbers of participants will be essential to consider the placebo effect. Consequently, most of the advancing institutions or intrinsic variables manifest intensely towards the placebo effect. Similarly, it is the same case with Migraine; whereby its massive subjective nature and the possibility of future improvements are vital potential problems for the effective interpretation outcomes of various trials. Continued involvement of obstinate Migraine patients in practices with increased neurological consultations in clinics on scalp injections of high-profile treatments creates elements of inevitable placebo effects massively. Besides, having faith in the chosen therapy by a therapist in the presence of the patients enhances increased means of pain control which eventually reduces the fixed treatment period.

Generally, the side effects of onabotulinumtoxinA are easily tolerable because all results experienced only cause little harm for a short period. However, Botulinum toxin type A is highly antigenic and may lead to massive reactions in the formation of antitoxin antibodies that may affect the long-term purpose of BoNT-A for Migraine treatment. For most Migraine patients who were injected with BoNT-A treatments, therapy failure was only effective temporarily for a short period. However, there is also an essential need to enhance longer treatments for Migraine patients to enhance effectiveness in preventing the severity of the disease [3]. A therapy failure caused by blocking onabotulinumtoxinA antibodies is a clinical issue repeatedly experienced for an extended period. Using Botulinum toxin type A to prevent pain in Migraine patients, side effects and other arising issues are very rare. The most common complications from these injections include; stiffness in the area of injection and neck pains. It is also possible for patients to develop headaches after undergoing a Botulinum toxin type A injection, and temporary muscle weaknesses on the upper shoulders and the neck, making it hard for patients to keep their heads upright. There is no specific cure for these side effects, but they are temporary situations, and they resolve after a short period. Also, at times Botulinum toxin type A toxin effects can affect other areas past the injection site, and the patient may experience the following; changes in their vision, drooping eyelids, raised eyebrows, problems in swallowing, and general muscle weaknesses [10]. Therefore, for Migraine patients to enhance increased health safety and avoid severe complications after Botulinum toxin type A injections, it is advisable to ensure the treatment is administered by an experienced and highly trained professional.

The most challenging issue in the ongoing investigations and studies on the effectiveness of using BoNT-A to prevent the severity of Migraine include; secrecy among the investigators and patients and also the side effects of the treatment. However, randomized controlled trials have continued to provide BT-medical evidence for the treatment. Still, to enhance crucial scientific progress, there is a need to comprehend the demerits associated with all investigative tools used during randomized controlled trials [11]. With all the theoretical limitations and advantages discussed and the potential of having a better understanding between test arms and placebo, it seems almost impossible to gather enough evidence towards the efficacy of Botulinum toxin type A in preventing Migraine severe pain from the increasing trials. Therefore, before any future appeals are made on clinical trials on Botulinum toxin type A and Migraine, there is a need to consider the following facets:

• The need to establish neuropeptide (CGRP or SP); towards the Dural inflammation caused by BoNT-A.

• The practical evaluation on the antidromic transfer of Botulinum toxin type A.

• Due to superficial needling or dry and pain relief, the clinical effects should be studied more critically in Migraine patients.

In conclusion, Migraine is a vital cause of disability problems worldwide; chronic Migraine reduces patients’ quality of life and is a prevalent condition. Currently, FDA has approved a fixed technique and follow-up clinic visits for BoNT-A pain injections that help to reduce the severity of Migraine and also reduce the duration of Migraine prevention or reduction in patients, and the techniques are essential to enhance pain relief for patients for a period of up to 12 weeks and above. Botulinum toxin type A (BoNT-A) has emerged as an interesting treatment option for a variety of health issues, including migraines. BoNT-A reduces muscular contractions and prevents neurotransmitters from passing pain signals to the brain, hence greatly lowering migraine pain. The treatment is highly effective, with a 65% response rate in migraine patients treated with BoNT-A after three sessions. BoNT-A treatment is safe and highly effective in avoiding migraine headaches, with a monthly decrease in the amount of headache and head pain medications provided to acute patients. Patients might have injections every 12 weeks, depending on their specific needs, even though the treatment’s benefits are temporary. Studies continue to demonstrate the usefulness of BoNT-A as a treatment for migraines, and the treatment continues to provide migraine patients the opportunity to live a life free of discomfort.

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