Auricular Vagus Nerve Stimulation For Fibromyalgia Syndrome
Condition: Fibromyalgia; Myofascial Pain Syndrome
MeSH terms: Fibromyalgia; Myofascial Pain Syndromes; Syndrome
Study type: Interventional

Summary: 
      The purpose of this study is to evaluate the impact of auricular vagus nerve stimulation,
      applied in conjunction with an exercise treatment program, on pain and life quality in
      patients with Fibromyalgia Syndrome (FMS). To achieve the study objectives, 60 female
      patients between the ages 18 - 50, with diagnosed FMS according to American College of
      Rheumatology (ACR) 2010 diagnostic criteria, were randomly divided into 2 groups of 30. The
      first group was assigned 20 sessions of a home-based exercise program, while the second group
      was assigned 20 sessions of auricular vagus nerve stimulation and 20 sessions of a home-based
      exercise program. Patients were assessed before and after the treatments using the Visual
      Analog Scale (VAS) for pain, Beck Depression Scale for depression, Beck Anxiety Scale for
      anxiety, Fibromyalgia Impact Questionnaire (FIQ) for functional evaluation and Short Form-36
      (SF-36) for life quality.

      In this randomized controlled trial, comparisons within the groups revealed that both groups
      had statistically significant improvements in pain, depression, anxiety, functionality and
      life quality scores (p<0.05), whilst comparisons across the groups revealed that the group
      experiencing the vagus nerve stimulation had no statistically significant differences between
      the baseline scores, except for those of SF-36's sub-parameters of physical function, social
      functionality and pain. In fact comparisons across the groups after the interventions
      revealed that the group experiencing the vagus nerve stimulation had better scores but not
      statistically significant. From analysis of this data, the investigators observed that vagus
      nerve stimulation in FMS treatment did not give additional benefit together with exercise,
      except for three sub-parameters of SF-36. It was identified that further studies which
      separately investigate the effects of vagus nerve stimulation and exercise on FMS with longer
      follow-up periods and an increased number of patients are needed.
    

Detailed description: 
      Fibromyalgia syndrome (FMS) is a syndrome, characterized by chronic widespread pain that
      continues for a minimum of 3 months and pain felt upon 11 out of 9 pairs of identified sore
      points. It is often accompanied by systemic symptoms such as fatigue, sleep disorders,
      cognitive dysfunction and depression . Moreover, headache, dysmenorrhea, irritable bowel
      syndrome, restless leg syndrome, chest pain, jaw pain, stomach ache, sensitive skin, mitral
      valve prolapses, Sicca symptoms, Raynaud phenomenon and female urethral syndrome accompany
      the clinical picture in many patients with FMS . This syndrome, the etiology of which is
      unknown, is commonly seen in women and the age of onset is usually 30 - 50 . Its prevalence
      among the general population is reported to be between 2.9 - 4.7 percent . While it is often
      seen in the adult population, it can also be observed in childhood or later age . Recent
      research studies show that various anomalies in genetic structure, autonomic nervous system
      (ANS), neurotransmitters, hypothalamic-hypophyseal-adrenal axe hormones, oxidative stress,
      pain modulation centers, central sensitization and muscular structure occur in FMS . The
      etiology of FMS is still not fully understood; nonetheless, the data reveals that this
      syndrome may stem from dysfunctionality in ANS . Sympathetic nervous system (SNS) dominance
      is widespread in FMS, chronic fatigue, irritable bowel syndrome and interstitial cystitis . A
      highly peripheral sympathetic tone causes regional ischemia, which in turn causes widespread
      pain. Therapeutic interventions that result in vasodilatation (e.g. exercise) and appropriate
      autonomic changes are proven to be effective for reducing pain levels .

      The "great and perfect protector" of the body, the vagus nerve includes a
      neuro-endocrine-immune network that ensures homeostasis. The vagus nerve, which has
      reciprocal neural connections with more than one region of the brain, serves a control center
      that combines sensitive information and provides appropriate feedback responses. Recent
      studies show that the vagus nerve also encompasses inflammation, mood and pain regulation.
      All of these can be modulated with vagus nerve stimulation. Vagus nerve stimulation can
      generate a neuromodulating effect to activate other natural protective paths to improve
      health . The development of vagus nerve stimulation began in the 19th century. A number of
      new electrical stimulation devices have now been developed. Non-invasive transcutaneal
      devices stimulate the vagus nerve through the auricular branch or from the carotid. Moreover,
      they are used in the treatment of various disorders, such as epilepsy, pain and headache .
      Recent pre-clinical studies have shown that vagus nerve stimulation heavily modulates pain in
      humans and is quite effective. The use of a medical device allows the auricular branch of the
      vagus nerve to be stimulated without surgical intervention. Consequently, it has been found
      that the threshold of pain is elevated and mechanical pain sensitivity is reduced .

      As a result of these completed studies, there is a possibility that FMS is a disease, which
      occurs through ANS impairment. Vagus nerve stimulation could be used as an additional
      treatment method to improve the ANS impairment. However, as there are no studies that
      investigate vagus nerve stimulation in FMS, this study is designed and executed.

      MATERIAL AND METHOD

      Our study, in which the researchers investigated the impact of auricular vagus nerve
      stimulation on pain and life quality in patients with FMS, was conducted in Beykoz Public
      Hospital's Department of Physiotherapy and Rehabilitation. A total of 60 female patients
      within the age range 18 - 50, with diagnosed FMS by a physiatrist according to 2010 ACR
      criteria, were included in this study. Only females were included to make groups homogenous
      and ended the age range at 50 to avoid comorbid illnesses seen in elderly people and also
      menopause. Pregnants, perimenopausal and postmenaopausal women are not included, also those
      experiencing any comorbid illnesses like neurological deficits, diabetes, neuropathic
      disorders, chronic inflammation, immune deficiency, cardiac disorders and current vitamin D
      intake were excluded from the study. In addition those who started using new drugs in the
      last month and during the study were not included. Patients who experienced vasovagal syncope
      in their past could not participate in the study.

      Ethics committee approval was awarded by the Ethics Committee of Beykoz State Hospital
      Clinical Research prior to the commencement of the study. Written consent forms were obtained
      from all patients to demonstrate their consent to being included in the study. Patients were
      assessed twice during the study, firstly before treatment and then after treatment. Before
      the assessment, data was obtained from patients relating to age, height, weight, occupation,
      level of education, marital status, regular medication, general health complaints and the
      duration of these complaints. All responses were recorded. Patients were also asked to not
      participate in any other treatments during the study, in order to prevent any external
      influences on the data and study parameters.

      Patients are diagnosed with FSM, in accordance with the ACR 2010 Diagnostic Criteria. A total
      of 60 patients are included in the study. Patients were randomly divided into two groups: an
      exercise (control) group and an exercise and vagus stimulation (treatment) group.
      Randomization was carried out by random number assignment. The exercise group began with 30
      patients and the exercise and vagus stimulation group began with 30 patients. By the end of
      the study, there were 25 patients in the exercise group and 27 patients in the exercise and
      vagus stimulation group. Five patients in the exercise group were excluded as they had not
      completed the exercise program. 3 patients in the exercise and vagus stimulation group failed
      to complete the study and they missed treatment sessions. There was no blinding in the study.

      The exercise group was assigned a program, which consisted of strengthening, stretching,
      isometric and posture exercises, targeting the body and upper and lower extremities. That
      program was home-based and the program was requested to be completed. Patients were asked to
      attend weekly face to face sessions with a total of 4 of these sessions in the study
      duration.

      Patients in the exercise and vagus stimulation group received auricular vagus nerve
      stimulation at Beykoz Public Hospital's Department of Physical Therapy and Rehabilitation on
      5 week days for 4 weeks, making up a total of 20 sessions with each session taking 30
      minutes. Patients were admitted to the treatment as day visitors. Vagus nerve stimulation is
      carried out with a TENS device, which has specially designed surface electrodes in the shape
      of earphones, the size of which can be selected according to ear size. Electrodes were placed
      to correspond with the inner and rear surfaces of the tragus and the concha for both ears .
      The application is carried out, for 30 minutes, using a biphasic, asymmetrical waveform with
      a pulse duration that is less than 500 microseconds and a frequency of 10 Hertz. Amplitude is
      adjusted according to the sensory threshold level. Patients in this group were also assigned
      the same home-based exercise program assigned to the patients in the exercise group with
      application of the program 5 days a week with 2 sets per day and each set involved 10
      repetitions of every exercise. Patients were asked to attend weekly face to face sessions
      with a total of 4 of these sessions in the study duration.

      Measurements were performed twice, before and after the treatments. Patients were asked to
      complete the Turkish version of the Fibromyalgia Impact Questionnaire (FIQ), consisting of 21
      questions, displaying the extent to which pain impacts the daily activities, social lives,
      moods and professional lives of the patients during the previous week.

      Pain intensity was evaluated within the context of this study using the Visual Analog Scale
      (VAS). Patients were asked to select the corresponding interval for their own intensity of
      pain on a table of 0-100 mm with the explanation that 0 refers to no pain and 100 is
      excruciating pain .

      Life quality of patients was evaluated using the SF-36 life quality scale. The Turkish
      validity and reliability of this scale was also carried out . Investigating life quality
      regarding overall health, this questionnaire contains 36 questions in 8 different categories
      .

      The level of depression of patients was evaluated using the Beck Depression Scale. The
      Turkish validity and reliability of this scale was carried in 1988. It is a questionnaire
      that consists of 21 questions with 4 items and each item is awarded between 0-3 points (18).

      The level of anxiety of patients was evaluated using the Beck Anxiety Scale.

      Statistical Analysis

      The presentation of variables acquired within the scope of the study such as sex, level of
      education and occupation includes numbers (n) and percentage values.

      The Shapiro-Wilk test is used to determine whether the variables in the study are congruent
      with the normal distribution. Interquartile range (IQR) values for the variables without
      normal distribution and average±SD (Standard Deviation) values for the variables with normal
      distribution are provided in the descriptive statistics.

      In the comparison of measurement values before and after the treatment, results of t-test for
      the variables with normal distribution and of Wilcoxon-Signed Rank test for the variables
      without normal distribution are provided.

      In the comparison of treatment group and control group after the treatment, results of t-test
      for variables with normal distribution and of Mann Whitney-U test for variables without
      normal distribution are provided.

      Chi-square and Likelihood Ratio Chi-Square tests were used to assess the relationship between
      patient and control group complaints, accompanying diseases, duration of pain and daily
      sports activities.

      IBM SPSS Statistics 21.0 (IBM Corp. Released 2012. IBM SPSS Statistics for Windows, Version
      21.0. Armonk, NY: IBM Corp.) and MS-Excel 2007 were used for statistical analyses and
      calculations. The level for statistical significance was accepted to be p<0.05.
    

Intervention name(s): Vagus nerve stimulator; exercise
Intervention type(s): Device; Other
Intervention description(s): Vagus nerve stimulation is carried out with a TENS device, which has specially designed surface electrodes in the shape of earphones, the size of which can be selected according to ear size. Electrodes were placed to correspond with the inner and rear surfaces of the tragus and the concha for both ears (Figure 1). The application is carried out, for 30 minutes, using a biphasic, asymmetrical waveform with a pulse duration that is less than 500 microseconds and a frequency of 10 Hertz.; The exercise group was assigned a program, which consisted of strengthening, stretching, isometric and posture exercises, targeting the body and upper and lower extremities. That program was home-based and the program was requested to be completed. Patients were asked to attend weekly face to face sessions with a total of 4 of these sessions in the study duration.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Fibromyalgia Syndrome; Auricular Vagus Nerve Stimulation