Asia Pacific Journal of Clinical Trials: Nervous System Diseases

STUDY PROTOCOL
Year
: 2019  |  Volume : 4  |  Issue : 1  |  Page : 17--23

Effects of galvanic vestibular stimulation versus cervical proprioception training on pain, pressure pain sensitivity, and joint position sense in patients with chronic neck pain: study protocol for a randomized controlled trial


Sayyed Hamed Fazeli1, Mohammad Akbari1, Ismail Ebrahimi Takamjani1, Holakoo Mohsenifar1, Amir Salar Jafarpisheh2,  
1 Department of Physical Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran
2 Department of Ergonomics, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

Correspondence Address:
Mohammad Akbari
Department of Physical Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran
Iran

Abstract

Background and objectives: Neck pain is a disabling condition associated with pain and proprioceptive disturbances. There is limited evidence on the efficacy of treatments for chronic neck pain (CNP). The aim of this study is to conduct a randomized, controlled trial to compare the effect of galvanic vestibular stimulation (GVS) with that of cervical proprioception training (CPT) on pain and proprioception acuity in patients with chronic neck pain. Subjects and methods: Forty-eight patients with CNP enrolled in this prospective, single-blind, randomized, controlled study will be randomly allocated to one of four groups: GVS, CPT, GVS + CPT, and control. The GVS group will receive galvanic stimulation, three sessions per week, for 6 weeks. The CPT group will perform proprioceptive exercises daily for 6 weeks. The GVS + CPT group will receive both interventions. The control group will have no intervention for 6 weeks, but 6 weeks later, they will receive physical therapy. In addition, 12 healthy subjects will be recruited. This study protocol has been approved by the Ethics Review Board of Iran University of Medical Sciences, with permission number IR.IUMS.REC 1395.9211342210 on August 8, 2016. Patient recruitment began in October 2016 and ended in October 2018. Data analysis will be performed in March 2019 and the study will be completed in May 2019. Outcome measures: The primary outcome measures will be intensity of pain, pressure pain threshold, and joint position error. The secondary outcome measures will be disability and health-related quality of life. Outcomes will be assessed at baseline and at the end of sessions 1 and 18. Discussion: Findings from the trial are expected to help assess the effectiveness of GVS, compared with CPT in patients with CNP. If this protocol is proven to be effective, it can be implemented in a clinical setting to manage chronic pain in patients with CNP. We expect this study to offer information about the positive effects of GVS and CPT. Findings from this study will be helpful in progressing GVS from science to practice and in managing disturbances in CNP. Trial registration: The study was registered at the Iranian Registry of Clinical Trials on September 26, 2016 (IRCT2016060121459N2).



How to cite this article:
Fazeli SH, Akbari M, Takamjani IE, Mohsenifar H, Jafarpisheh AS. Effects of galvanic vestibular stimulation versus cervical proprioception training on pain, pressure pain sensitivity, and joint position sense in patients with chronic neck pain: study protocol for a randomized controlled trial.Asia Pac J Clin Trials Nerv Syst Dis 2019;4:17-23


How to cite this URL:
Fazeli SH, Akbari M, Takamjani IE, Mohsenifar H, Jafarpisheh AS. Effects of galvanic vestibular stimulation versus cervical proprioception training on pain, pressure pain sensitivity, and joint position sense in patients with chronic neck pain: study protocol for a randomized controlled trial. Asia Pac J Clin Trials Nerv Syst Dis [serial online] 2019 [cited 2019 Mar 19 ];4:17-23
Available from: http://www.actnjournal.com/text.asp?2019/4/1/17/251478


Full Text

 Introduction



Neck pain is a common complaint, with half of people experiencing at least one episode of neck pain in their lifetimes (Fejer et al., 2006). Cervical pain is often recurrent, with no clear and exact cause. It can affect social and occupational life (Côté et al., 2009; Hogg-Johnson et al., 2009; Hoy et al., 2014). Pain in the neck region is a pathological condition associated with increasing disability in the general population (van der Windt et al., 2002; Picavet et al., 2003). Neck pain is considered chronic if it lasts longer than three months. The persistent insufficiency of neuromuscular control contributes to chronicity and recurrent cervical problems (Falla et al., 2007). Evidence-based treatment for chronic neck pain (CNP) is limited to therapeutic exercises, manual therapies, and acupuncture (Haller et al., 2016).

Patients with CNP have many sensorimotor disturbances, such as proprioception deficiency, motor control changes, and muscle imbalances (Falla et al., 2007). Therefore, a multimodal treatment approach has been recommended to improve sensorimotor control (Falla et al., 2007; Haller et al., 2016; Izquierdo et al., 2016). Impaired postural control and impaired proprioception are usually associated with neck pain, and there are several treatment methods aimed at influencing these impairments, such as cervical proprioception training (CPT) and balance training (Kristjansson et al., 2009). These exercises have resulted in enhanced sensorimotor control and reduced neck pain and disability (Revel et al., 1994; Jull et al., 2007). However, it is not clear whether this treatment approach also has an effect on other aspects of neuromuscular function in people with neck pain (Falla et al., 2004).

Neck muscles provide proprioceptive afferent input on body orientation, body segment position, posture, and gait; thus, accurate assessment of neck proprioception is important (Pettorossi and Schieppati, 2014). Revel et al. (1991) devised a test to evaluate the ability to sense neutral cervical joint position, called the “head relocation test”.

Recent research has highlighted the essential role of the vestibular system in motion perception, eye movement, body orientation, and postural control (Maitre and Paillard, 2016). The vestibular system is a multimodal sensory system that is involved in many functions, including reflexes, perception, and consciousness (Maitre and Paillard, 2016). Vestibular afferent information may influence the reliance attributed to other sensory information (Ferrè et al., 2013). The vestibulo-ocular and vestibulospinal reflexes are essential for maintaining stable vision and posture.

The central nervous system (CNS) integrates the vestibular, visual, and proprioception afferents to maintain an upright stance (Massion, 1994; Cenciarini and Peterka, 2006). An altered CNS, in combination with vestibular afferents and other sensory information, can impact movement coordination, vertigo, spatial disorientation, and perceptual illusions (Clément and Wood, 2014). Head displacements during sport activities may elicit acute vestibular illusion of motion (i.e., erroneous perception of head motion), generating sensory conflicts between visual and vestibular systems, which results in spatial disorientation (Grunfeld et al., 2000; Clément et al., 2001, 2007).

When sensory afferents are disrupted, the CNS activates compensatory strategies such as sensory reweighting and feed-forward mechanisms to preserve balance (Massion, 1994; Cenciarini and Peterka, 2006; Maitre and Paillard, 2016). Exercise training can have a positive impact on the CNS's ability to trigger these mechanisms. Among CNP patients with sensory disturbances, if other sensory sources are augmented, the specific CNS ability of switching from one sensory source to another sensory source can improve (Kiers et al., 2013). In this study, we will activate the vestibular system through galvanic vestibular stimulation (GVS), thereby potentially improving the CNS's switching mechanism.

GVS is a cost-effective and safe way to use direct current (DC) to activate the fibres of the vestibular nerve via skin-mounted electrodes placed over each mastoid process. This technique modulates activation of vestibular afferents (i.e., the cathodal current causes an increase in the firing rate of vestibular afferents, whereas anodal current causes a decrease in their firing rate) in a similar manner to natural head movement (Fitzpatrick and Day, 2004; Rizzo-Sierra et al., 2014).

Interestingly, there is growing scientific evidence that supports the use of GVS as a novel and powerful neurorehabilitation measure. Given the role of vestibular information in many reflexes and sensory afferent processing, as well as the involvement of vestibular afferents in pain processing, in this study we will compare the effectiveness of GVS to that of CPT on pain, in patients with CNP.

The aim of our study is to investigate the comparative effectiveness of two treatment methods for improving cervical proprioception acuity and associated pain over 6 weeks. This will be accomplished by comparing the effects of GVS to those of CPT. This study will be also performed to assess the effects of the two interventions on the neck disability index (NDI) and the 12-Item Short From Health Survey (SF-12) for disability and health-related well-being.

 Methods/design



Design and setting

A prospective, randomized, analyst-blinded, controlled trial will be conducted to compare GVS with CPT. The trial will involve a 6-week treatment period. After randomization, patients in a GVS group will receive 18 sessions of stimulation over a period of 6 weeks. A CPT group will be trained daily for 6 weeks. A GVS + CPT group will receive both GVS and CPT. A control group will not undergo intervention during the 6 weeks [Figure 1]. The study will be conducted at motion analysis laboratory in Iran University of Medical Sciences.{Figure 1}

Outcome measures will be assessed at baseline (that is, after CNP diagnosis), immediately after session 1, and at the end of the sixth week after randomization [Table 1].{Table 1}

This study protocol has been approved by the ethics review board of Iran University of Medical Sciences, with permission number IR.IUMS.REC 1395.9211342210. The study was registered at the Iranian Registry of Clinical Trials (IRCT2016060121459N2). Participants will be informed orally and in writing about the procedures. Written informed consent will be obtained before data collection commences.

Recruitment

Some participants will be referred from neurosurgeons. Posters will be put up for recruitment of patients and healthy subjects in buildings around the university. In addition, advertisements will be placed in social media. Patients will be provided trial information, and written consent form will be obtained from patients and prior to inclusion.

Study population

Inclusion criteria of patients

Male and female patients will be included if they fulfil the following criteria: (1) complaint of neck pain for 3 months or more, (2) aged 20–50 years, (3) no history of head or neck trauma, (4) no referral pain in upper limbs, (5) NDI score greater than 10%, and (6) Visual Analogue Scale (VAS) score 3 or greater than 3 (placed 3 cm or more away from the “no pain” endpoint).

Exclusion criteria of patients

Patients with any of the following conditions will be excluded: (1) neurological disorders; (2) cervical spine root compression, radiculopathy, or connective tissue disease; (3) cervical fracture or dislocation, ankylosing spondylitis, myelopathy, or cervical spine surgery; and (4) use of physiotherapy treatment within 3 months prior to study entry.

Randomization and allocation concealment

Patients who meet the inclusion criteria will be randomized into four groups: GVS, CPT, GVS + CPT, and control. The computer-generated random numbers method will be used to randomize patients into groups. In addition, 12 healthy subjects will participate in this study. An independent statistician will produce a computer-generated randomization sequence, which will be placed in sequentially numbered, sealed opaque envelopes. The randomization sequence will allocate equal numbers of participants to each group [Figure 1].

Blinding

Participants and statistician will be blinded to group allocation. Unblinding inevitably results in the exclusion of the respective participant.

Baseline measures

All patients are requested to complete the questionnaire and consent form. Baseline information including sex, age, height, and job will be collected.

Interventions

A physiotherapist (SHF) with 12 years of experience will perform all the interventions during the study.

GVS

Bilateral bipolar stimulation will be used to apply current through the head by placing a cathode just behind one ear on the mastoid process and an anode behind the other ear on the other mastoid process. A low, direct current (exponential stimulation) will be delivered, with ramp up and ramp down, via circle electrodes on the mastoid processes using a DC stimulator (PHYSIOMED ELEKTROMEDIZIN AG, 91220 Schnaittach, type vocastim Nr VSM-0203507 gb, Germany). Participants will perform an individual threshold detection task prior to the experiment. During this task, a current, increasing in 0.10-mA steps from 0–5 mA (duration 1 second, rest 3 seconds), will be applied, and patients will be asked to report when they start to feel dizzy and sense head movement to one side. Thereby, patients’ thresholds will be determined in terms of GVS amplitude. The polarity of the stimulus will be randomized across trials. The current will increase to the threshold value and will be stabilized for the remaining time. The stimulation will be applied for 10 minutes while the patients’ eyes are closed. Subjects will sit upright in a chair, with their feet on the ground, shoulder-width apart, their knees bent at a 90° angle, and their heads in a neutral position. The maximum amplitude of direct current during the 6 weeks will be limited to below 5 mA to ensure safety. GVS will be performed three sessions per week for 6 weeks.

CPT

Patients will be trained to perform three categorized proprioception exercises as reported (Revel et al., 1991, 1994; Falla et al., 2004; Pettorossi and Schieppati, 2014). Cervical proprioception exercises will include head relocation, oculomotor exercise, and eye-head coordination.

For head relocation exercises, patients will sit in a chair, with a laser pointer attached to a helmet at the apex of their head. A target will be placed at the eye level on a wall 90 cm away. This will be defined as the neutral head position. Patients then will return their head to the neutral head position after active neck movements, first with eyes open using feedback from laser attached to the head and then with eyes closed. All active movements of the spine of the neck (flexion, extension, rotation, lateral flexion) will be performed.

Oculomotor exercises program will perform through two stages. First, eyes will follow a target located at a comfortable distance with the head stationary. Second, head will move with visual fixation on a target (i.e., gaze stability).

Eye-head coordination exercises will be started initially by moving the eyes and head to the same side, both left and right. After that, patients will follow a target with the eyes first, then with the head, keeping them focus on the target. This exercise will be performed with eye movement first and then head movement to look between two targets positioned horizontally or vertically, and finally, the eyes and head will rotate in opposite directions, both left and right. All these exercises will progress by increasing the speed and range of motion of the target and with patients in a standing position.

Patients will receive six physiotherapist-supervised sessions during a 6-week study period by the same physical therapist. All patients will receive a daily exercise and will be asked to practice twice per day for a 6-week study period. They will be instructed to perform their exercise in the same way that they will be trained during their supervised sessions. The exercise session at home takes no longer than 20 minutes per day and no provocation of pain will be permitted.

Primary outcome measures

PPT evaluation

PPT will be evaluated bilaterally at cervical muscle sites, including the upper trapezius (UT) and suboccipital (SO) muscles, using a digital algometer (Commander, JTECH Medical INDUSTRIES, 7633 S Main St, Midvale, UT 84047, USA) with a flat circular compression tip (1 cm2). The algometer probe tip will be applied perpendicularly to the skin at a rate of 3 N/s. Three tests will be conducted on each site with a 30-second rest between tests. A mean of three PPT measures will be used for analysis.

A familiarization phase will precede the formal measurements. During this phase, patients will be instructed regarding procedure, and the examiner will practice with them at a remote site (forearm). Subjects will be trained to indicate the moment when pressure changed to pain, corresponding to the definition of the PPT.

Participants will sit for testing of the UT and SO sites. To ensure consistent application of the pressure algometer, two markers will be placed on each site. For the UT site, the markers will be on the midpoint between the C7 vertebra and on the acromion along the UT muscle belly. For the SO site, markers will be placed on the right and left articular pillars between C1 and C2 (approximately 1 cm lateral and above the spinous process of C2). Participants will be informed that the evaluation will be used to determine their pain thresholds, not their pain tolerance; therefore, they will be asked to inform the therapist as soon as they first feel pain.

Pressure algometry is a valid and reliable method to measure PPT (Vanderweeen et al., 1996), with studies showing good repeatability of measurements on the neck muscles (intra-correlation coefficient 0.78–0.93) (Ylinen et al., 2007).

Pain

The participants’ subjective feelings of pain will be measured using a 10-cm VAS, anchored with “no pain” and “the worst pain imaginable”. Participants will be asked to mark along the 10-cm line the point that best represents their current painful symptoms. The VAS will be administered at baseline, after the first treatment session, and at the end of the 6th week (after session 18) when the intervention will be completed.

The VAS is a commonly used measure in similar studies and has been assessed as having a moderate to good level of reliability, particularly when assessing severe pain (Murphy et al., 1987; Scudds, 2001).

Joint position sense

Joint position sense will be evaluated using the JPE test, which is considered the primary measure of neck proprioception and has been commonly used as an outcome measure in patients with CNP (Revel et al., 1991). The general assumption has been that poor performance on this test reflects abnormal neck afferent input (Revel et al., 1991).

A laser pointer will be fixed on the top of a helmet that participants will wear during measurements; participants will sit in a standard chair placed 90 cm away from a wall, where the target (a sheet of A3 millimetric paper) will be fixed.

The movements to be used in the JPE test are right and left rotation of the neck, and extension. Before beginning the test, participants will rest their heads in a neutral position, which will be marked on the target (where the light of the laser pointer falls on the sheet of paper). From this position, participants will be asked to rotate their heads to the left or right, to move their heads backward from a flexed position in their pain-free range, and then to return to the initial neutral position, which will be marked again on the target. Between trials, the examiner will manually adjust the participant's head to match the original starting position, giving no feedback on accuracy. Each participant will perform 3 trials of each movement. Additionally, one familiarization trial will be conducted before measurements are taken.

The laser method has a good test-retest reliability and strong correlation with an ultrasound technique (Roren, 2009).

Secondary outcome measures

Disability and health-related quality of life

The NDI and the SF-12 will be used as secondary outcome measures. To date, the NDI has been the most extensively used questionnaire in clinical trials and prognosis studies. The NDI has also been used to assess subjective symptoms and disability in activities of daily living associated with neck pain.

The NDI consists of 10 six-part questions, in the following sections: section 1, pain intensity; section 2, personal care; section 3, lifting; section 4, work; section 5, headaches; section 6, concentration; section 7, sleeping; section 8, driving; section 9: reading; and section 10, recreation. Each question has 6 choices, reflecting a range from “no disability” to “severe disability” (0–5). Individual questions will be summed to scores out of 50, where higher numbers represent worse morbidity. The final scores will be calculated by summing all scores and will be presented in the form of a percentage from 0 to 100%, depending on the number of questions answered by the subjects. The Iranian version of the NDI questionnaire will be used to assess disability related to neck pain. The questionnaire has good short-term repeatability and internal consistency (Mousavi et al., 2007).

The SF-12 was developed as a shorter, more practical version of the SF-36 questionnaire to permit its application in large health studies, with focus on overall physical and mental health outcomes. The SF-12 includes 12 questions and 8 scales. Studies using the SF-12 have verified the questionnaire as a valid and reliable measure for evaluating overall community health status (Andrews, 2002). The Iranian version of the SF-12, whose reliability and validity was assessed (Montazeri et al., 2009), will be used in this study.

Data collection and management

The patient pain intensity will be marked on a 10-cm line. Joint position error will be collected from marked points on A3 millimetric paper. PPT records will be written on paper. The data will be statistically analyzed by statisticians.

Statistical analysis

Sample size

The sample size will be determined based on a study by Izquierdo et al. (2016), which evaluated the effect of a cervical exercise program on PPT patients’ self-reported levels of pain, disability, and PPT. Izquierdo et al. calculated the sample size for their study and reported that, for a statistical power of 0.80 and an α level of 0.05, a total sample size of 24 patients was required, with 12 patients for each group. Therefore, in this study, 60 participants will be divided into five groups: four experimental groups (12 patients with CNP in each group) and one healthy group (12 asymptomatic participants). Participants will be recruited via advertisements and referrals from two neurosurgeons in Tehran.

Analysis

A statistician from the University of Social Welfare and Rehabilitation Sciences (Tehran, Iran) who is blind to allocation of groups will guide and assist with the statistical analyses. Statistical analyses will be conducted using SPSS version 21 (IBM Corp., Armonk, NY, USA), and results will be considered significant at the P < 0.05 level. Measurements will be taken at three time points: baseline (pre-intervention), immediately after the first treatment session (post-session 1) and the end of treatment session (post-session 18). Prior to statistical comparisons, all data will be examined for normal distribution using the Shapiro-Wilk test.

Healthy participants and patients’ PPT, JPE, pain intensity, disability, and health-related quality of life at baseline will be compared using the independent samples t-test for parametric and Wilcoxon test for nonparametric distribution. For comparison of the differences between and within groups, a mixed-model analysis of variance will be used.

Means and standard deviations will be shown for normally distributed dependent variables. An intention-to-treat analysis will be performed to analyse the effectiveness of the two interventions. Intention-to-treat analysis will involve participants who have received at least one treatment session. Baseline characteristics and primary and secondary outcomes will be analysed based on the intention-to-treat principle. For variables that do not conform to the assumption of normality, the analysis will be performed using the Mann-Whitney U test.

Patient safety

Any adverse effects, such unintended symptoms including dizziness, vertigo, and headache, will be monitored, although the interventions that will be used in this study are safe. All research protocols, safety, and adverse effects will be reviewed by the investigation group. The trial will be stopped if there are concerns for patient safety.

Controlling bias

To minimize bias, randomization, concealed allocation, specific inclusion and exclusion criteria, patient blinding, blind data analysis, and intention-to-treat analysis will be used. It is not possible to blind the physiotherapists performing the interventions.

Monitoring

Trial progression will be reported to the ethical committee every 6 months. The trial will be supervised by an independent monitoring board that is not involved in the design of the trial or in the recruitment of patients.

The researchers should provide costs of treatment and financial compensation for subjects suffering damage associated with the trial.

Ethics and dissemination

This study protocol has been approved by the ethics review board of Iran University of Medical Sciences, with permission number IR.IUMS.REC 1395.9211342210 (Additional file 1) [SUPPORTING:1] and adheres to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines (Chan et al., 2013) for protocol reporting (Additional file 2) [SUPPORTING:2]. The study will be performed in accordance with the Declaration of Helsinki. Written informed consent (Additional file 3) [SUPPORTING:3] will be obtained from participants before data collection commences.

The results of this trial will be published in peer-reviewed scientific journals and presented at relevant academic conferences.

 Discussion



This study will be the first to assess the effectiveness of Galvanic Vestibular Stimulation compared with that of Cervical Proprioception Training in patients with CNP. In previous research, CPT has been found to improve proprioception and joint position accuracy (Izquierdo et al., 2016), but there is little research investigating the effect of GVS on proprioception and pain in CNP patients. Thus, this study will compare the efficacy between GVS and CPT. Given the connection of the vestibular system to many brain areas and the various resulting roles, the findings regarding the effects of GVS obtained in this study may provide evidence for GVS improving proprioception disturbances and pain in CNP patients. By revealing whether GVS or CPT has more positive effects, this study could enable practitioners to make better clinical decisions in CNP.

In addition, if a therapeutic effect of the vestibular system activation associates with proprioception training, it may also prove clinically helpful in reducing CNP.

Trial limitations

With the absence of research-related facilitators of study recruitment (e.g., research assistant facilitated recruitment), there may be high rates of missing data, and completer rates may be smaller than those in typical efficacy trials.

 Trial Status



Subject recruitment is ongoing.

Additional files

Additional file 1: Ethical approval documentation.

Additional file 2: SPIRIT 2013 checklist.

Additional file 3: Model consent form.

Author contributions

Study design: SHF, MA, IET, HM; methodological considerations: SHF, MA, HM; statistical analysis: ASJ; manuscript drafting: SHF. All authors contributed to manuscript writing and approved the final manuscript.

Conflicts of interest

The authors declare that they have no competing interests.

Financial support

This study received no specific grant from any funding agency.

Institutional review board statement

This study protocol has been approved by the ethics review board of Iran University of Medical Sciences, with permission number IR.IUMS.REC 1395.9211342210. The study will be performed in accordance with the Declaration of Helsinki, and informed consent will be collected from each participant prior to enrollment.

Declaration of participant consent

The authors certify that they will obtain all appropriate participant consent forms. In the forms, the participants will give their consent for their images and other clinical information to be reported in the journal. The participants understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Reporting statement

This study follows the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for protocol reporting.

Biostatistics statement

The statistical methods of this study were reviewed by the biostatistician of School of Rehabilitation Sciences, Iran University of Medical Sciences, Iran.

Copyright license agreement

The Copyright License Agreement has been signed by all authors before publication.

Data sharing statement

Results will be disseminated through presentations at scientific conferences and/or by publication in a peer-reviewed journal. Individual participant data will not be available. However, the study protocol and informed consent form will be made available following article publication to investigators.

Plagiarism check

Checked twice by iThenticate.

Peer review

Externally peer reviewed.

Open access statement

This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

C-Editor: Zhao M; S-Editor: Li CH; L-Editor: Song LP; T-Editor: Jia Y[35]

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