Introduction
Migraine is a benign headache affecting nearly 12% of the adult population worldwide [1]. As a diagnostical and differential marker, a person with migraine headache should experience at least five attacks that cause unilateral, pulsating headaches of moderate to severe intensity that last between 4 to 72 hours. Additional symptoms, such as vomiting, photophobia, or nausea accompany this condition. The intensity of the headache increases with routine activities or while walking up or down stairs, reducing the ability to perform routine daily tasks [1, 2]. The origin of migraine as a neurovascular condition can be related to vascular, central nervous system, and peripheral contributors that can sensitize the peripheral nervous system [2]. Risk factors, such as hypertension, smoking [3], and the consumption of medication drugs for other problems can initiate or aggravate symptoms [4].
Pharmacotherapy as a primary treatment for migraine may be curative or prophylactic. However, only about half of the patients with this disorder have a clinically significant response to preventive pharmacotherapy treatments, and more than 10% of patients refuse to continue the treatment process due to interactions with other medications or long-term side effects [5].
Considering that migraine is a multifactorial problem, patients may have musculoskeletal system dysfunction [6]. Many of the migraineurs have cervical muscle dysfunction. Disorders, such as forward head posture, reduced range of motion of the neck, and increased sensitivity of the neck muscles may be observed [7]. Some of these changes are also called myofascial trigger points (MTrPs) [8]. MTrPs are irritable points in the taut band that develop in skeletal muscles or fascia and can cause local sensitivity and referral pain when compressed [9]. These points can contribute to muscular impairment, such as lower strength and endurance, altered recruitment patterns, motor control, and a limited range of motion of the involved joint [10, 11]. MTrPs in specific muscles, such as the sternocleidomastoid (SCM), suboccipital, and upper trapezius (UT), could initiate or at least aggravate the characteristics of migraine headaches [12, 13]. Additionally, the referred pain zone of active MTrPs in these muscles is similar to the areas affected by migraine headaches [13]. As one of the major muscles in the cervical region, the UT plays a role in cervical movement and has high potency in developing MTrPs. Referral pain of MTrPs in the UT feels unilateral upward along the posterolateral aspect of the neck and extends to the temple and the back of the orbit [13]. A positive correlation is observed between the number of MTrPs in temporal and suboccipital areas and the frequency and duration of migraine attacks [7]. Furthermore, UT-induced irritation of MTrPs in migraineurs may initiate migraine headache symptoms [14].
Dry needling (DN), a known physiotherapy intervention used to deactivate MTrPs, is defined as the penetration of a fine needle into the skin, subcutaneous tissues, and muscle to release MTrPs [15]. DN may have beneficial effects on reducing pain perception, improving blood circulation, and promoting the secretion of endogenous opioids, such as β-endorphin, which affects the nervous system and may impact headache characteristics during pharmacotherapy [9, 16]. However, evidence on releasing MTrPs and their impact on headache characteristics in patients with migraine headaches are limited. To the best of our knowledge, only one study has investigated the impact of releasing MTrPs with the DN technique in patients with migraine headaches. In this study, the DN technique was performed on MTrPs of SCM, and as the results showed, SCM-DN can have positive effects on the clinical parameters of headache (intensity, duration, and frequency); therefore, this technique can be considered a cost-effective complementary treatment to improve the quality of life (QoL) of patients with migraine headaches [6]. Although this study has provided valuable results regarding the effectiveness of the DN technique in the treatment of migraine patients, the impact of the DN on SCM-MTrPs cannot be generalized to other muscles [6], especially UT-MTrPs, whose referral pain can mimic and cause migraine headaches [13].
Although releasing MTrPs of the UT muscle seems to have positive effects on headache characteristics [13, 17], more studies need to be conducted about the effectiveness of MTrP-DN of UT in migraineurs. Therefore, this randomized controlled trial aims to investigate the impact of the MTrP-DN of the UT on migraine headaches and evaluate its possible effects on migraine headache characteristics, such as frequency, duration, medication drug consumption, and intensity, along with MTrP characteristics, such as the pressure pain threshold (PPT) and pain intensity at the MTrP.
The primary objective is to determine the effects of DN on UT-MTrP plus pharmacotherapy compared to pharmacotherapy alone on headache intensity in patients with migraine headaches, reported by the daily headache diary form. This study secondarily aims to determine the impact of DN on the UT-MTrP plus pharmacotherapy compared to pharmacotherapy alone on headache frequency, duration, and drug consumption, all of which will be assessed by the daily headache diary form. MTrPs sensitivity or the PPT will be evaluated by algometer, and the pain intensity of UT-MTrPs while applying pressure by algometer will be assessed by the visual analog scale (VAS).

Materials and Methods

Study design
This protocol is a single-blinded, randomized control trial with parallel groups of 40 patients. The study protocol was created following SPIRIT guidelines [18]and registered under IRCT20200215046499N2, with the registration on 2021-12-06. It received approval from the Research Ethics Committee of Tabriz University of Medical Sciences, with the registration code IR.TBZMED.REC.1400.430, which was approved on 2021-08-02. Patient recruitment, assessment, and treatment will be performed at a public hospital (Table 1). The Physiotherapy Department is liable for monitoring the study process from its initial to its final stage. The study team considered no interim analysis for this study. No auditing trial has been predicted in this study. After considering any changes in the protocol, the recent approach will be edited at Iranian Registry of Clinical Trials (IRCT).






Participants
The subjects in this study included adults who suffered from migraine headaches and had MTrP (according to Travell and Simons’ definition of MTrP) in the UT muscle of the affected side [13]. These patients were diagnosed according to the International Classification of Headache Disorders (ICHD-3) [19] and referred by a neurologist to the physiotherapy clinic of a public hospital under the supervision of an expert physiotherapist with 15 years of clinical experience in treating headaches. Using G*Power software, version 3.1.2 with the parameters of effect size: 0.8, α error probability: 0.05, and power: 0.80, 40 patients were determined for two groups (20 patients for each group). The effect size of the present study was determined according to the study of Ghanbari et al., and the mean and standard deviation of the headache intensity variable were determined [20].

Study procedure
MTrP diagnosis and DN treatment were performed by a physiotherapist who is a professional in MTrP treatment and certified in releasing MTrPs with the DN technique. According to Travel and Simon’s criteria, an active MTrP is determined by the existence of a taut band in the muscle, an irritable tender point in the taut band, spontaneous pain, local twitch response (LTR) with compression, and familiar referral pain, which is reproduced by irritating the point [13]. Recruitment began by interviewing patients referred by neurologists with a diagnosis of migraine. The assessor of the study completed the assessment process in terms of the eligibility criteria if subjects were eligible to participate in the study considering the inclusion and exclusion criteria (Table 2) and having MTrP in the UT muscle, they were informed about possible benefits, harms, and objectives; if they were interested in participating, they would sign the written informed consent form. After the participants were included in the study, their demographic data were collected, including the following items: Age, gender, weight, height, medication history, drug usage, and side of headache. Then, the participants were randomly allocated into intervention and control groups via sealed envelopes. The participants in the intervention group received three sessions of DN treatment with an inter-session interval of 1 week plus pharmacotherapy, and those in the control group received only pharmacotherapy. The duration of the study program for the intervention and control groups was the same (Figures 1 and 2).



Someone outside the study team randomized participants with a simple randomization method by sealed envelopes. Two envelopes were prepared with A & B titles. Each participant randomly selected one envelope, and the letters of the envelopes were recorded for that participant. Then, envelopes were set beside each other, and the next participant repeated the same procedure until all participants were randomly divided into two groups. It was conducted by someone outside the research team with a 1:1 parallel allocation method that used a computerized randomization program to assign participants to groups, using blocks of four and six. After that, the allocation of groups was enclosed and hidden in opaque envelopes sealed with prelabeled letters A and B. Someone outside the study team performed the recruiting procedure. The outcome assessor was blinded to the intervention type and should be blinded during the study without any excuses. Unmasking events were recorded while the participants were performing the study. After completing the recruiting and treatment procedure for all participants, the outcome assessor could be informed about the group allocation if they were willing to.




Therapeutic interventions
The intervention group received routine pharmacotherapy plus three sessions of DN on the most irritable MTrP of UT at one-week inter-session intervals. The patient should lie in prone to perform the DN technique on the UT. The taut band is taken with the thumb and index finger of the nondominant hand, and the needle is directly inserted into the MTrP of the muscle with the dominant hand. The needle should move back and forth to elicit LTR until the LRT is not visible by moving the needle ten times. The MTrP location is marked with a waterproof marker so that the location of this point remains constant during the three sessions of the DN. If more than one painful point is observed, the point with the most pain will be selected. In addition, participants in the intervention group received migraine pharmacotherapy so that they were not deprived of their routine treatment. As the neurological doctor neurologist prescribes, the participants in both groups take drugs like propanol, which has a prophylactic effect. Sodium valproate and topiramate act as anticonvulsants: Amitriptyline, nortriptyline, and other tricyclic antidepressants (TCAs). The prescription of drugs and their dosage depends on the intensity of their headache daily drug usage and their possible interactions. Participants in the control group only received pharmacotherapy.  
The absence of two successive treatment sessions or the unwillingness to participate in the treatment procedure excludes the patient from the study, and a substitute patient replaces the excluded patient. To improve adherence to treatment protocol, all treatment costs are free for participants, and they can contact their therapist and ask questions about their clinical symptoms over the phone. The participants in the intervention group are allowed to take analgesics, such as acetaminophen or ibuprofen if tolerating pain becomes difficult [21]. On the other hand, if pain tolerance after treatment sessions is not possible for patients to perform their daily tasks, the treatment procedure must be stopped. The confidentiality principle is considered at every trial stage and remains confidential after trial results are published. If any adverse situation occurs during the trial, intentionally or unintentionally, the research team is responsible for the harm caused. The adverse effects of DNs can be divided into two categories: Minor (i.e. pain, bleeding, and bruising) and major (i.e. pneumothorax, excessive bleeding, and syncopal responses) (Table 3) [22]. Fortunately, the TP-DN technique is a relatively safe treatment [22, 23]. 




Outcomes measures

Headache parameters
The headache intensity, as well as its frequency, medication drug consumption, and duration, are evaluated by the daily headache diary. Scoring based on the headache diary varies from 0 to 4. Score 0 indicates the absence of a headache, score 1 indicates a headache only when the person pays attention to it, score 2 indicates that the occurrence of headache does not interfere with the person’s daily activities, score 3 indicates a headache, tasks that require concentration cannot be performed, and score 4 indicates that the headache interferes with many daily tasks and only essential tasks can be performed [24]. In the intervention group, the daily headache diary form is completed by participants at baseline, before the DN technique in sessions 2 and 3. In the control group, the daily headache diary form is conducted at the first and second sessions (14 days after the first session, which equals the third treatment session in the intervention group). Participants in the control and intervention groups are evaluated by completing the daily headache diary form 30 days after the last session (follow-up session). The form is delivered to the therapist in person after being completed by the participants.
The patient reported headache frequency based on headache attacks per week with the daily headache diary form in both the intervention and control groups [21]. The procedure used to report the frequency of headaches in the intervention and control groups is similar to the headache intensity.
The headache duration represents the duration of the headache from its onset to its end and is assessed by the headache diary form in both the intervention and control groups [24]. The procedure for reporting the headache duration for the intervention and control groups is similar to that for headache intensity.
Drug consumption is reported in headache diary form in both the intervention and control groups. The procedure of reporting the drug consumption in the intervention and control groups is similar to those used to assess headache intensity.

PPT
PPT is evaluated by a digital algometer in the intervention group, before the initiation of the intervention, immediately after the intervention, and in every treatment session; in the control group, PPT is assessed once at the first session and once at the second session (equal to the third treatment session in the intervention group). This outcome is not measured in the follow-up session. A digital algometer (FPX 25 Algometer Wagner Instruments, Greenwich, USA) assesses PPT. The procedure is explained verbally to the patient to introduce the patient to how the PPT is assessed. Once the patient understands the assessor’s explanations, the algometer is placed vertically on the MTrP of the UT muscle, and the pressure is increased at a constant rate (an increase of one kilogram per square centimeter of pressure per second). When the patient says “this,” the assessor should stop increasing pressure, and the value displayed on the screen of the algometer is recorded. For reproducibility, the exact location of MTrPs is marked with permanent ink. This process is repeated thrice with intervals of 10 s, and the average value is used in data analysis. The reliability of the assessment using the pressure algometer device is reported to be good to excellent (interclass correlation coefficient [ICC]=0.75–0.89).

Pain intensity of the MTrP
The VAS evaluates the pain intensity of the UT-MTrP. In the intervention group, the VAS is assessed before the intervention and immediately after the intervention in every treatment session. In the control group, the VAS is assessed first and once during the second session.

Statistical analysis
The blinded outcome assessor records participants’ personal information, baseline, and outcome measures on the assessor’s laptop. The outcome data is saved in an Excel file for analysis. No decision for further analysis has been made in this study. Protocol nonadherence or loss to follow-up is handled by intention-to-treat analysis. Descriptive statistics, including the Mean±SD for quantitative variables, is performed for the dependent variables by SPSS software, version 26. Examining the conformity of the frequency distribution of quantitative variables with the theoretical normal distribution is conducted through the Shapiro‒Wilk test and skewness. The data transformation method is used if the data distribution is not normal. To compare the variables between the first and the follow-up session in the control and intervention groups, a paired t-test is used, or to compare the variables between the two groups in the first session and the follow-up session, an independent t-test is used. Repeated measures compare the variable changes between therapeutic sessions in the intervention group. The acceptable P=0.05 in this study.

Results
After completing the study procedure, the results are ready for publication in an international peer-reviewed journal and will be presented at prominent national or international conferences.

Discussion
Although migraine headache is a benign type of headache, it can be debilitating and affect different aspects of a person’s QoL during the attack [25]. Drugs from pharmaceutical families, such as beta-blockers, anticonvulsants, and TCAs, are usually prescribed to treat and reduce the negative parameters of migraine headaches [26-28]. Despite the effectiveness of such drugs, half of the patients reported dissatisfaction with their conventional pharmacotherapy. On the other hand, the tolerance and side effects of currently available medication drugs often limit their use [28].
Due to the multifactorial nature of this issue, impairments in different systems, such as the blood circulation, central nervous system, and peripheral nervous system, can be considered as aggravators of its symptoms [2]. Considering this feature, a compound treatment program that targets different perspectives on this issue may have a more positive effect than pharmacotherapy alone. On the other hand, nociceptive inputs of the myofascial system (MTrP) in muscles, such as the UT, SCM, and suboccipital muscles, can be considered an influential factor in aggravating migraine symptoms, and their release may improve the migraine headache characteristics [6, 7, 12, 29].
DN, as an effective treatment in releasing MTrPs, may have positive effects on the nervous system (central and peripheral) by activating neuron fibers, such as Aβ fibers, Aδ fibers, and C fibers, and the secretion of substances, such as endogenous opioids [30-32], by releasing substance P and calcitonin-generated peptide, DN can improve blood circulation [33-36] and regulate spontaneous electrical activity by causing LTR. Although DN seems to be an effective method to release MTrPs, evidence supporting this therapeutic method and investigating its effects in patients with migraine headaches is scarce [6].
This is the first study to determine the impact of releasing the MTrP of UT muscle in addition to pharmacotherapy and to explore whether the DN of UT as a complementary treatment can benefit routine pharmacotherapy in patients with migraine headaches.

Conclusion
The final data of the study will be published after the completion of the study procedure. 

Ethical Considerations

Compliance with ethical guidelines
The trial is recognized and registered in the Ethics Committee of Tabriz University of Medical Sciences with the Ethics Committee (Code: IR.TBZMED.REC.1400.430, approved on August 2, 2021). Based on the Declaration of Helsinki, the following ethical principles will be considered during the trial: 1) The study’s goal, characteristics, and duration were informed to the participants, who signed an informed consent form to enter the study. 2) Collected information, including personal and study-related data, was protected, maintained confidentially, and used only for statistical analysis. 3) Participants were free to withdraw from the research at any stage and for any reason, or even without providing a specific reason. 4) The researcher committed to compensating any potential costs incurred by the participants due to their involvement in this study. 5) The possibility of allocation into each group was explained to participants before their assignment to the study. This trial was registered prospectively in the Iranian Registry of Clinical Trials (IRCT) (No.: IRCT20200215046499N2; registered on December 6, 2021).

Funding
Although this study is conducted under the supervision of the Rehabilitation Sciences Faculty at Tabriz University of Medical Sciences, the study team has not received any funding from the University or any other organization for any study stage.

Authors' contributions
Conceptualization: Neda Najafi, Amin Momenzadeh, Hakimeh Adigozali, and Mandana Rezaei; Methodology, and supervision: Hakimeh Adigozali, and Mandana Rezaei;  Investigations, and writing the original draft: Neda Najafi and Amin Momenzadeh; Review and editing: Bahram Amirshakeri, and Mohammad Yazdchi; Final approval: All authors.

Conflict of interest
The authors declared no conflict of interest.

Acknowledgments
The authors’ team appreciates the Tabriz University of Medical Sciences, Tabriz, Iran, for providing the required setting for this trial.




References