Ehlers–Danlos syndrome (EDS) is a connective tissue disorder characterized by joint hypermobility and skin extensibility and is often accompanied by chronic pain. Rhythmic sensory stimulation (RSS) can be defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain. In this current study, we conducted an open-label pilot study of 15 patients with hypermobile EDS using RSS as the intervention. Posttreatment improvements were seen in 11 of the 15 patients (73%), whereas 3 of the 15 patients (20%) experienced worse outcomes. Of the 14 patients that completed the experiment, 6 participants (43%) were classified as “responders” to the device while 8 participants (57%) were classified as “nonresponders.” Responders demonstrated significant improvements in pain interference (51.5 ± 16 preintervention vs. 43.5 ± 16.4 postintervention BPI score) and depression symptoms (34.0 ± 15.9 preintervention vs. 26.8 ± 12.1 postintervention CESD score). Poststudy interviews confirm the improvements of pain interference, mood, and bowel symptoms. Furthermore, analysis of medical conditions within the responder group indicates that the presence of depression, anxiety, irritable bowel syndrome, and fibromyalgia may indicate a greater likelihood for patients to benefit with vibroacoustic applications. These results indicate a possible potential for RSS, delivered using a vibroacoustic device, in managing pain-related symptoms. Further research is necessary to elucidate the exact mechanism behind the physiological benefits of RSS.
Ehlers–Danlos syndrome (hEDS) is a congenital, heterogeneous group of connective tissue disorders characterized by joint hypermobility and skin extensibility [
Several theories have been proposed to explain the mechanism(s) of chronic pain. Melzack and Wall’s gate control theory (GCT) involves a bottom-up approach which posits that stimulation of peripheral nerves by nonnoxious stimuli can impede the transmission of painful stimuli [
Rhythmic sensory stimulation (RSS) is defined as the stimulation of the senses in a periodic manner within a range of low frequencies. Music plus low-frequency sound delivered through a vibroacoustic device is a form of RSS and has demonstrated utility in managing pain [
Although research using RSS has been conducted within an array of conditions, little research has focused on chronic pain in hEDS. In a previous single-case study of a patient with hEDS [
A total of 15 participants entered the study, and 14 completed the study. The inclusion criteria comprised the following: (1) a clinical diagnosis of hEDS by the clinical staff at Mount Sinai Hospital’s Wasser Pain Management Centre and Medical Genetics Department or a completed and signed referral form by health care practitioners indicating diagnosis; (2) joint hypermobility; (3) confirmed joint dislocations; (4) a Beighton score of 5 or more out of 9; (5) ongoing chronic pain of at least 6 months; (6) the ability to read and write English adequately; (7) self-reported satisfactory bilateral hearing; (8) the ability to operate the supplied RSS device, the Sound Oasis VTS1000, and to pick up and return the device at the Wasser Pain Management Centre.
The exclusion criteria were as follows: (1) serious concomitant illnesses, such as malignancy and vertebral fracture; (2) active inflammatory conditions, such as spinal infection and ankylosing spondylitis; (3) history of pathological fracture; (4) pregnancy; (5) coccydynia; (6) metabolic bone disease; (7) bleeding or clotting disorder; (8) hypotension; (9) active psychiatric disorders, such as bipolar disorder, schizophrenia, severe/psychotic depression, or anxiety disorder (at the discretion of clinicians/health care practitioners instead); (10) the use of pacemakers, implanted defibrillators, or neurostimulators.
A one-group pre-post treatment design was implemented. There were three assessments. The first assessment served as a baseline before study initiation and utilized four self-reported measures, including the Brief Pain Inventory, Short Form (BPI-SF) [ BPI-SF: the brief pain inventory assesses the severity of pain and the impact of pain on daily functions. Although first made for cancer patients, it is reliable and valid for assessing noncancer-related pain [ POMS-SF: the profile of mood states is used to measure psychological distress. A five-point scale ranging from “not al all” to “extremely” is administered, and a number from 0 to 4 is associated with this scale in a direction depending on the type of questions. Greater scores are associated with worse conditions. Reliability and validity for the POMS have been conducted [ SF-36: the short form healthy survey measures the quality of health and is commonly used in health economics to calculate cost-effectiveness of a health treatment. The SF-26 consists of eight scaled scores that are weighted sums of a section of questions. Each scale is converted into a 0–100 point value in which a lower score indicates more disability and a higher score indicates less disability. Reliability and validity for the SF-36 have been conducted [ CES-D: this is a brief self-report to measure depressive symptoms. The questionnaire consists of 20 questions, scores from 0 to 3, totaling 0–60 points. Higher scores indicate greater depressive symptoms. Reliability and validity for the CES-D have been conducted [ PGI-C: PGI-C consists of one item that measures the change in patient health. The range is 0–7 with a score of 1–3 indicating improvement, 4 being no improvement, and 5–7 being worse after the treatment. Reliability and validity for the PGI-C have been conducted [
Secondary endpoints included changes in scores from time of treatment termination to the final assessment following the washout period. Qualitative analysis was conducted on the responses from the semistructured interviews to explore patients’ experience and perceived effectiveness of the RSS system for managing pain and mood. Open-ended questions from semistructured interviews included the following questions: Can you please tell me about your experience with using the RSS system? Have you started any new treatments to help manage your pain since you began this study 4 weeks ago? (probe: type of treatment, duration of treatment, and effectiveness of treatment) Have you changed your medication regime since you began this study 4 weeks ago? (probe: reduced or increased dose, added medication, removed medication, and switched medications) If you have changed your medication regime, why did you do so? (probe: change in prescription, side effects, difference in pain, mood, or sleep levels) Did you experience any negative side effects using the RSS stimulation system? (probe: if yes, what were the most bothersome side effects) Did you notice any positive effects/changes that you feel are a result of using the RSS system? (probe: improvement in pain levels or sleep, changes in behaviour, attitude, coping methods, emotions, and relationships) What did you dislike about using the RSS stimulation system, if anything? (probe: inconvenience, frequency or duration of use, vibrations, music, and comfort of chair) Would you choose to use the RSS system in the future? (probe: if yes, how often) On a scale of 0–10 with 0 representing not helpful at all and 10 representing extremely helpful, how helpful do you feel the RSS system was in helping you manage the severity of your pain? On a scale of 0–10 with 0 representing not helpful at all and 10 representing extremely helpful, how helpful do you feel the RSS system was in improving your mood? On a scale of 0–10 with 0 representing not helpful at all and 10 representing extremely helpful, how helpful do you feel the RSS system was in helping you manage daily activity levels?
To analyze and present this qualitative data, all answers were compiled and categorized into common phrases represented by 1-E2 words, counted, and then presented in bar graphs as a percentage of the total number of participant responses for each question of interest.
During this 4-week study, patients were given an RSS device (Sound Oasis VTS1000) which they self-administered daily for 30 minutes, five days per week. The patients were instructed to select a time of day to use the RSS device; however, it was recommended that participants use the RSS device in the morning and use it consistently at the same time. The patients were given a diary in order to record their usage and the presence or absence of side effects.
Participants were instructed to place the device on a bed or chair, turn the device on, and choose the “Energize therapy session” program that is supplied on this commercially available device. “Energize” comprises of three tracks (41 Hz to 73 Hz with 41 Hz dominant; 36 Hz to 61 Hz with 41 Hz dominant; and 36 Hz to 65 Hz with 55 Hz dominant). The music uses the bass, guitar, piano, and digital keyboard and features mono and binaural high alpha and beta entrainment. A somatosensory vibration generated by an audible low-frequency sound wave can be felt from the shoulders to the low-back, and relaxing but not “ambient” instrumental music can be heard prompting the participant to begin timing their 30-minute session. Patients were instructed to turn the low-frequency sound driven vibration intensity to 15 and the volume level of the music to 1 or 2. However, participants were informed that if discomfort was experienced due to these settings, they were to adjust the vibration and volume level to alleviate the discomfort. Participants were asked to note any deviations to the recommended procedure in the diary.
All patients consented to the study after being provided a clear description of the study and their rights of participation, withdrawal, and confidentiality. The study was conducted in accordance with the principles set out in the Declaration of Helsinki [
Descriptive statistics including percentages, means, and standard deviations were used to report demographic data such as age, gender, pain location, and pain duration. Data were analyzed by comparing baseline, posttreatment, and washout measurements using repeated measures ANOVA analysis. Interview answers were compiled, and common keywords or phrases were derived from each answer, counted, and then presented as a percentage of total participants. Outcomes were analyzed using SPSS for Windows, version 22, with 5% as the significance threshold.
A total of 15 patients with hEDS were recruited for participation, of which 14 completed the intervention and poststudy interviews. The average age was 35.8 years (SD = 13.2 years), ranging from 23 to 59 years. All patients were female and reported the presence of a concomitant condition such as depression, anxiety, or chronic pain conditions. More than half of the patients were either married or in a relationship. The demographic and clinical characteristics have been described in Table
Patient demographics.
hEDS patients ( | ||
|
||
Age | 35.8 ± 13.2 | |
Sex | 100% F | |
Ethnicity | 93.3% Caucasian | |
Marital status | 8 (53.3%) single | |
2 (13.3%) common law | ||
3 (20.0%) married | ||
2 (13.3%) divorced | ||
|
| |
Headache | 13 (86.7%) | |
Spontaneous dislocations/subluxations | 13 (86.7%) | |
Chronic back pain | 12 (80.0%) | |
Depression | 10 (66.7%) | |
Irritable bowel syndrome | 10 (66.7%) | |
Flat feet, fallen arches, neuromas, and plantar fasciitis | 10 (66.7%) | |
Anxiety | 9 (60.0%) | |
Chronic pelvic pain | 8 (53.3%) | |
Insomnia | 8 (53.3%) | |
Chronic facial pain | 5 (33.3%) | |
Fibromyalgia | 5 (33.3%) | |
Dysautonomia | 5 (33.3%) | |
Mast cell activation syndrome | 4 (26.7%) | |
Thyroid condition | 4 (26.7%) | |
Cracked, weak, or crowded teeth | 4 (26.7%) | |
Raynaud's syndrome | 3 (20.0%) | |
Chiari malformation | 1 (6.7%) | |
Other |
6 (40.0%) |
Posttreatment improvements in both pain interference and depression were seen in 11 of the 15 patients (73%) (Figures
Subject-by-subject analysis of pain interference and mood in response to the intervention. (a) Line graph depicting the subgroup of patients that demonstrated improvements in BPI from preintervention to postintervention. (b) Subgroup of patients that demonstrated adverse BPI from preintervention to postintervention. (c) Subgroup analysis of patients that demonstrated improvements in CES-D from preintervention to postintervention. (d) Subgroup of patients that demonstrated adverse CES-D from preintervention to postintervention.
Comparison of mean scores across time for all patients (
Outcome measure | Preintervention | Postintervention | Washout |
|
---|---|---|---|---|
BPI-severity | 27.15 ± 6.8 | 25.5 ± 7.3 | 26.5 ± 4.5 | 0.293 |
BPI-interference | 49.9 ± 13.7 | 46.1 ± 14.0 | 43.6 ± 12.4 | 0.089 |
CES-D | 28.5 ± 14.2 | 26.2 ± 12.2 | 25.6 ± 11.3 | 0.458 |
POMS_total | 49.23 ± 25.56 | 50.08 ± 30.00 | 44.46 ± 22.81 | 0.483 |
SF_overall | 126.92 ± 94.90 | 151.92 ± 89.83 | 144.23 ± 77.83 | 0.146 |
Analysis was done by repeated measures ANOVA. Numbers represent mean and standard deviation,
Qualitative analysis of poststudy interviews indicated that 57% of patients reported the device to have a positive effect on their quality of life, with 21% reporting a neutral effect and 21% reporting a negative effect (Figure
Summary of poststudy interview. (a) Overall experience of patients. (b) Response to use the intervention again. (c) Common answers to the open-ended question about positive effects. (d) Common answers to the open-ended question about negative effects.
The analysis of individual data points along with poststudy interviews indicated that the experience of the RSS device varied among hEDS patients, with a small subset of patients reporting their symptoms worsening. Therefore, we were interested in determining the minimal clinically important difference (MCID) to report how many patients experienced a meaningful change after treatment. Following the procedure outlined in a review on MCID, the PGI-C scale was used to determine the MCID (a score of “3” or better) [
Comparison of mean scores across time for all responders (
Outcome measure | Preintervention | Postintervention | Washout |
|
Effect size (partial |
---|---|---|---|---|---|
BPI-severity | 24.2 ± 7.8 | 21.2 ± 6.7 | 24.3 ± 3.7 | 0.234 | 0.252 |
BPI-interference | 51.5 ± 16 | 43.5 ± 16.4 | 44.5 ± 11.2 | 0.028 |
0.510 |
CES-D | 34.0 ± 15.9 | 26.8 ± 12.1 | 28.5 ± 10.0 | 0.031 |
0.499 |
POMS_total | 51.83 ± 27.06 | 45.33 ± 28.72 | 43.67 ± 20.20 | 0.31 | 0.211 |
SF_general | 141.67 ± 106.85 | 162.50 ± 102.16 | 150.00 ± 75.83 | 0.44 | 0.151 |
Analysis was done by repeated measures ANOVA. Numbers represent mean and standard deviation. No significant findings for POMS-SF or SF-36.
Analysis of effects of the intervention on pain interference and mood for responders. (a) Line graph depicting BPI-severity scores in patient responders at all time points in response to the intervention. (b) BPI-interference scores in patient responders in response to the intervention. (c) CES-D scores in patient responders in response to the intervention.
To study the difference between responders and nonresponders in more detail, an analysis of the prevalence of concurrent medical conditions was conducted and this yielded a potentially important observation (Figure
Histogram depicting the percent of total responders or nonresponders that reported having each medical condition. Nonresponders are represented in black bars, and responders are in grey. The
The present study investigated the effects of rhythmic sensory stimulation on pain and mood symptoms of hEDS patients. Our findings revealed that 43% of hEDS reported benefit from using RSS in their symptoms. The proportion of hEDS responders to this RSS treatment is similar to the proportion of fibromyalgia responders (40%) in a previous study that used a similar protocol [
Consistent with the initial case report, we found that pain interference is significantly improved (i.e., reduced) in responders without significant changes in pain severity. Furthermore, poststudy interviews reveal that one of the common positive benefits of the device was muscle relaxation. This suggests that the vibrotactile sensation produced by the RSS device could have improved mobility-related pain and functionality, which has been demonstrated in previous studies using low-frequency stimulation [
We also found significant improvements in depression symptoms in responders after using the intervention. Improvements seen in mood symptoms may be due to improvements seen in pain interference, as this increases the types of activities that patients can engage in and thus improves quality of life. However, the cognitive and affective effects of music also play a major role, increasing dopamine and serotonin levels in the brain and improving mood symptoms more directly [
An additional consideration is the evidence for aberrant neural oscillations that have been associated with the sensation of chronic pain [
Auditory and vibrotactile RSS can be an additional tool to reduce hEDS symptoms including pain, mood, sleep, and potentially bowel movements. hEDS patients that report these particular symptoms may be more likely to benefit from 40 Hz of auditory and vibrotactile, while a small percentage of patients may find it discomforting. Further research is necessary to elucidate the mechanisms underpinning the physical and psychological effects of RSS.
The data used to support the findings of this study are included within the article.
V. V., A. M., D. P., L. P., H. F., M. E., and A. G. declare that there are no conflicts of interest. L. B. has served as a paid scientific consultant to Somerset Group and Sound Oasis and receives limited royalties from the Somerset Group for the Sonic Aid series and from Sound Oasis on the sales of the Vibroacoustic Therapy System VTS-1000 device.
The authors thank the patient advocate, Kathleen Eubanks, who is a representative of Ehlors–Danlos syndrome, Canada. She has helped give input on the design of the study as well as read through the manuscript draft for review. The authors acknowledge the University of Toronto, Mount Sinai Hospital, and Canadian Institutes for Health Research-Strategy for Patient Oriented Research (CIHR-SPOR) and Canadian Pain Network (CPN).