The Effect of Spinal Manipulative Therapy on Heart Rate Variability and Pain, and the Predictive Value of Conditioned Pain Modulation
Phase: NA
Conditions: Neck Pain
Sponsor: Karolinska Institutet

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The effect of Spinal Manipulative Therapy 
on Heart Rate Variability and pain in 
patients with chronic neck pain: A 
Randomized Controlled trial  
 
Anders Galaasen Bakken  
Intervention & Implementation Research for Worker Health         
Institute of Environmental Medicine                     
Nobels väg 13                                                                    
S- 171 77 Stockholm    
    
Iben Axén  
Intervention & Implementation Research for Worker Health         
Institute of Environmental Medicine                     
Nobels väg 13                                                                    
S- 171 77 Stockholm       
 
Andreas Eklund  
Intervention & Implementation Research for Worker Health         
Institute of Environmental Medicine                     
Nobels väg 13                                                                    
S- 171 77 Stockholm       
 
Søren O’Neill 
University of Southern Denmark 
Campusvej 55 
DK- 5230 Odense 
 
 
Clinical Trials Identifier: NCT03576846 
 
 

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Abstract  
Background 
Recent experimental research has suggested that Spinal Manipulative Therapy (SMT) may reduce pain 
through modulation of the ascending pain signals and/or the central pain regulating mechanisms. 
People with persistent neck pain (NP) have also been found to have disturbances in Autonomic Nervous 
System (ANS) regulation. A common way to study ANS is to measure heart rate variability (HRV). It is not 
known if deviations in HRV are related to changes in pain perception or to the treatment response to 
SMT.  
Commonly, an individual in pain will experience pain reduction when exposed to a second pain stimulus, 
a mechanism known as Conditioning Pain Modulation (CPM). Patients with persistent pain have been 
found to have a reduced CPM reaction. It is not known if this is predictive of treatment response to SMT. 
The aim of the study is to examine the effects of SMT on HRV and pain and to test if a CPM test can be 
used to predict treatment response, in a population of patients with recurrent and persistent NP. 
Method/Design 
A multicentre randomized controlled clinical trial will be carried out in multidisciplinary primary care 
clinics. This setting is chosen to minimize bias resulting from patient preference to treatment modality 
and provider. 
The subjects are either self-referred or referred from other health care practitioners locally. The 
treatment modalities are two well-known interventions for NP; SMT and stretching exercises compared 
to stretching exercises alone. 
The subjective pain experience will be investigated by assessing pain intensity and the affective quality 
of pain. HRV will be measured using a portable heart monitor and CPM will be measured with a 
standardized cold-pressor-test. Measurements will be performed at baseline, prior to the third 
treatment and after the fourth treatment.  
Discussion 
The study will utilize normal clinical procedures, which should aid transferability and external validity of 
the results. The study will provide knowledge regarding the underlying mechanisms of the effects of 
SMT. Furthermore, the study will examine if a CPM test is predictive of treatment outcome in a 
population of patients with recurrent and persistent NP. 
Trial registration 
Clinical Trials: NCT 03576846, Registered 3. July 2018. 
https://clinicaltrials.gov/ct2/show/NCT03576846?cond=neck+pain&cntry=SE&city=Stockholm&rank=2 
Keywords 
Pain, Heart Rate Variability, Conditioned Pain Modulation, SMT, Chiropractic, Neck Pain 

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Background 
Musculoskeletal pain is a global burden due to a high prevalence and substantial costs worldwide (1). 
The most common conditions are low back pain (LBP) and neck pain (NP) (2). Despite years of research, 
diagnosing LBP and NP is still difficult, and up to 90 % of the cases are termed “non-specific”. This often 
results in treatments that are based on untested theories, e.g. theories of spinal dysfunction, instability 
or muscle weakness, but also on the preference of the healthcare provider and patient. Ideally, the 
diagnosis should rest upon an understanding of the pain mechanism (3), but due to the “non-specific” 
diagnosis of LBP and NP, a therapist will often not be able to select the most appropriate treatment for 
the individual patient. This may be the explanation for the moderate treatment effect sizes for most 
available treatments, potentially wasting resources and failing to improve patients’ health (4). 
Chiropractic care including Spinal Manipulative Therapy (SMT) has been found to be a safe, effective, 
and cost-effective non-invasive treatment for some types of spinal pain (5-7). SMT has both local and 
regional pain-reducing effects (8), as well as central nervous system effects such as a general reduction 
of pain sensitivity (9).  
SMT is thought to decrease pain by mechanically affecting muscular and joint function, i.e. normalising 
muscle tone and improving joint mobility. However, recent experimental research has suggested that 
SMT may also be influencing the incoming/ascending pain signals (local nociceptive input affecting 
dorsal horn excitability or temporal summation) and/or the excitability of the central pain regulating 
mechanisms (9, 10). A systematic review concluded that short-term sympathetic up-regulation can be 
found with SMT, regardless of the spinal area being treated (11). This raises the question of whether the 
pain reducing effect of SMT is associated with a modulation of autonomic nervous system (ANS) activity. 
Differences in ANS activity have been found between healthy controls and people with NP (12). In 
healthy individuals, acute pain results in an increased sympathetic response and often an increase in 
pain threshold induced by descending inhibition. However, in patients with chronic pain, it appears that 
persistent sympathetic activation could lead to hyperalgesia due to a decrease in descending inhibition 
(12). Further, in a recent study, chronic pain was reduced after treatment aimed at normalizing the ANS 
through biofeedback (12). This indicates a bidirectional relationship; ANS not only reacts to pain but pain 
is modulated by ANS activity. Furthermore, two studies (13, 14) (without control groups) have shown an 
association between positive treatment effects on pain and an increased Heart Rate Variability (HRV). 
HRV is mainly considered a proxy for ANS regulation, as it will depend on the balance in the autonomic 
system. 
Stretching is used both as a passive treatment intervention and as active home exercises for several 
conditions relating to the musculoskeletal system. The rationale behind stretching is to improve range of 
motion, reduce pain and perceived stiffness (15). The effect of stretching exercises in combination with 
other treatment modalities has been found to be a decrease in pain and disability in patients with NP (4, 
16). 
As mentioned above, chiropractic treatment is considered non-invasive and safe (5-7). Common benign 
and short-lasting reactions to SMT are mild to moderate increases in pain in the area of treatment often 

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coupled with fatigue (17), considered “normal reactions”. It has been shown that a normal reaction to 
treatment is a predictor for a good outcome (18), but the mechanism behind this is not known and 
appears not to have been previously studied or described in the literature. It may be hypothesized that 
the mechanisms behind normal reactions following SMT may also be explained by ANS reactions. 
The research in the area so far suffers from some limitations: Small group-sizes, possible patient bias  
(positive expectations) towards the therapist and treatment method, short follow-up time and lack of a 
reasonable comparator treatment. A randomized design with a standardised control treatment would 
distinguish treatment effects from contextual effects. In order to study the neurological effect of SMT 
and stretching exercises compared to stretching alone in patients with persistent and recurrent NP in a 
clinical setting, a sufficiently large sample and a randomized design should be used. In order to study 
long term HRV responses, measurements over 2 weeks will be conducted. 
Interestingly, when exposed to pain, a different noxious (painful) stimulus can be used as a conditioning 
(inhibitory/facilitatory) stimulus. The normal reaction is reduction in pain perception known as ‘pain 
inhibits pain’ or inhibitory conditioned pain modification (CPM). In patients with chronic pain, a reduced 
CPM response prevents the normal reaction to a painful stimulus to occur, and patients will not 
experience the normal “pain-inhibits-pain” reaction (19). 
In the study, a tool previously described in the literature (20) will be used to test the CPM response. The 
aim is to study if patients with reduced CPM prior to starting treatment will respond differently to a 
series of chiropractic treatments than patients with functioning CMP, i.e. to study if a test for CPM and 
its’ results can be used as a predictor of treatment outcome. Cold Pressor Test (CPT) is known to be a 
safe testing method with minimal adverse reactions (21). 
 
Method/Design 
Study aim 
The study aim is to determine the effects of a treatment series consisting of stretching and SMT on HRV 
and pain in a clinical setting in a population of patients with recurrent or persistent NP. A secondary aim 
is to test CPM as a predictor of treatment outcome. 
Setting 
This multicentre randomized controlled clinical trial will be carried out in multidisciplinary primary care 
clinics where physiotherapists and chiropractors are consulted for musculoskeletal pain. These types of 
clinics are selected to minimize bias from patients having expectations towards a specific treatment 
modality. 
A total of 6 clinics will take part in this study, and each clinic will include 20 subjects, resulting in 120 
subjects in total, 60 in each treatment arm. 
Two research trained clinicians will conduct all the measurements. 
The treatments (both intervention and control) will be delivered by clinicians (licenced chiropractors) in 
the participating clinics. 

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Eligibility criteria 
Inclusion criteria: minimum 18 years old, able to read and understand Swedish. The presence of 
recurrent (at least one previous episode) and persistent (duration more than 6 months) NP, and no 
chiropractic treatment during the previous 3 months. This interval was chosen as research have shown 
that similar treatments seem to have little effect beyond three months (22). 
Exclusion criteria: conditions or medications that will affect the HRV measurements such as 
cardiovascular disease, hypertension, diabetes, pregnancy, obesity (BMI >30), currently using pain-
reducing medication on a daily basis, steroids, beta-blockers or antidepressants. All contraindications to 
SMT, i.e. anything that could seriously aggravate the pain (e.g. inflammatory conditions) or be indicative 
of cerebrovascular injuries (previous drop attacks or a recent episode of a new headache or dizziness) 
will exclude the patient from the study. 
Procedure (Please see flow chart, fig. 1. and 2.) 
The clinics’ receptionists will schedule potentially eligible patients for the study visit in the study. A 
standardized form with inclusion/exclusion criteria will be used to assess eligibility. Logistical details of 
this recruitment stage will be adapted to individual clinic routines. 
If eligible and willing to participate, subjects will return on a later day, the study visit. They will be 
informed about the aim of the study and about the study procedures by a research assistant, sign an 
informed consent form and have their baseline measurements taken. Then, they will be randomized to 
one of the treatment arms and treated accordingly.  On the day of the study visit, the participants will 
refrain from caffeine, nicotine, alcohol, pain medication and from performing strenuous exercise. 
A standardized protocol is followed on the day of the study visit: After consenting to participate, the 
subjects will start by filling out baseline questionnaires for demographic information. They will also 
answer questions concerning their NP (duration, episodes, intensity and frequency) as well as questions 
regarding pain levels and the affective quality of pain using the NRS-11 scale (23, 24), STarT Back (25, 26) 
and the short-form McGill Pain Questionnaire (27, 28). Pain will be measured as average pain over the 
last 24 hours.  
The equipment used to measure HRV is called FirstBeat (https://www.firstbeat.com/sv/). It is applied by 
the research clinician, and the participants will rest quietly for 5 minutes with the equipment attached 
before baseline resting values are ascertained over a period of 5 minutes. Finally, CPM will be tested 
with a structured CPM test (29). This test includes mechanical pressure point intensity and a cold 
pressor test (20). When the patients leave, the HRV-equipment will still be attached to their chest, so 
that a continuous measurement can be done during the day and the following night, to record HRV 
through the deepest sleep.  
After the measurements, study subjects are randomized into one of the two treatment arms. Their 
allocated clinician will conduct a standard anamnesis and examination procedure including neuro-
orthopaedic tests to further assess exclusion criteria. The treatment protocol is then initiated according 
to allocation. All subjects will be scheduled to a treatment series consisting of 4 visits over 2 weeks. 

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Data on normal treatment reactions (tiredness/fatigue and pain/tenderness) are collected the day after 
the first treatment using SMS (https://www.sms-track.com/) to ascertain the type and level of reactions 
to the interventions (30, 31). 
Before the subjects’ third treatment, a second measurement of HRV and CPM will be conducted, and 
measurements of pain will be ascertained, using the standardized protocol used at the initial visit. 
Before the patients’ fifth treatment, or at least two days after the fourth visit, the final measurements 
will be conducted, this time the HRV-equipment will be taken off directly after the measurement. Again, 
the standard questionnaire measuring pain will be answered. 
After the study period (4 visits), the clinicians are free to select any other treatment modality for the 
patients. However, patients will be monitored with questionnaires every other week (via email) 
regarding their affective quality of pain and pain levels for 2 months after their final measurement at the 
clinic. The clinicians will also report what treatment modalities were used after the initial two weeks of 
the study. 
Patients who do not complete the full treatment plan will be asked to complete all measurements in 
order to study attrition and to complete a drop-out analysis.  
 
 
Figure 1. Flow chart of the study procedure  

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Randomization procedure 
Consecutively numbered opaque envelopes containing group allocation are created off-site at the 
research centre by a statistician. A 1:1 allocation ratio in randomly permuted blocks of different sizes 
according to a randomization schedule is used. SPSS v20 is used to generate the randomization code. 
The envelopes are opened consecutively by the treating clinician. 
Blinding 
The subjects will be unaware of what treatment the other group is receiving, as they will be told that the 
study is testing two different treatment modalities with similar clinical benefit to examine the effect 
over two weeks on physiological parameters and pain. Subjects in both treatment arms should feel that 
complying with their treatment plan during two weeks is a necessity for their improvement. 
It will not be possible to blind the clinicians performing the treatments. The research clinicians who will 
collect the data in the experiment will be blinded to the treatment allocation. The statistical analysis will 
be performed with the treatment allocation blinded. 
Sample size 
In a recent study that examined the reliability of HRV measures, the sample size was estimated to 20 
subjects in each group to detect a mean HRV change of 20%, and 20-50 subjects in each group to detect 
Figure 2. Spirit figure  

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a change of 10% (32). 10-20% difference has been considered to be clinically important (32). Also, a 
difference of 10-30% in resting HRV has been found between pain free subjects and subjects with work 
related NP (33). This value has also been used by other researchers investigating changes in HRV from 
manual treatment (34). With a significance level of 5%, it was estimated that 60 subjects were needed in 
each treatment arm to reach a power of 80%. A high number of dropouts is not expected in this study as 
it is conducted using an effective practise-based research network with established and tested routines 
developed to minimize the burden on participating patients. 
 
Treatment arms 
SMT in this study is defined both as a High-Velocity-Low -Amplitude (HVLA) thrust applied to the target 
joint, and also spinal mobilization (MOB) where the application of manual force to the spinal joints is 
within the passive range of joint motion and does not involve a thrust (35). This can include a variety of 
techniques targeting spinal joints. The type of techniques applied will be decided upon and described by 
the participating clinicians (chiropractors), and both SMT and MOB will be considered manual 
treatments as they have been found to have similar effects on several pain parameters in a recent 
multicentre study (36). This also provides the possibility for the chiropractor to adapt the force applied 
to the individual patient, which is normally done in the clinical encounter. 
The common modality used in both treatment arms is a program of home stretching exercises. Both 
groups will receive both verbal and written instructions describing the home stretching exercises that 
have been recommended as a low-cost first instance intervention for NP (additional file no.1) (16). 
Patients will be instructed to keep an exercise diary to monitor their exercise frequency (additional file 
no.1) (16). 
The same clinician will be performing all the treatments for each subject under his or her care (entire 
treatment plan and both modalities), to ensure consistency of the treatments across the study. 
The testing of HRV and CPM will be conducted by the two research clinicians, to ensure consistent high 
quality throughout the study. The two research clinicians will meet several times in advance of the study 
to test and calibrate the examination procedures and their communication with the study subjects. 
 
Outcome measures 
Experimental measures 
HRV, the variation in beat-to-beat heart rate, is an indicator of parasympathetic and sympathetic 
modulation of the heart rhythm. Deviations in HRV have been found in patients with both acute and 
chronic pain. Patients with various chronic pain conditions show reduced parasympathetic activity at 
rest, the proposed mechanism behind central sensitisation (37). Thus, vagus activity, assessed through 
HRV, is suggested to correlate with pain severity and could possibly be used as a proxy for treatment 
efficacy in patients with chronic pain (37). There are some studies showing that SMT influence HRV, but 
the quality is questioned (38). 

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CPM consists of the evaluation of a painful test stimulus followed by a second evaluation either at the 
same time as a distant, painful conditioning stimulus (parallel stimuli) or in series after the painful 
conditioning stimulus has been withdrawn (sequential stimuli) (19). CMP is a well-known concept in 
modern medicine, particularly when it comes to prediction of post-operative pain (39). It has been  
suggested that a dysfunctional CPM response can be a pathogenic factor in the development of chronic 
pain, but also that a dysfunctional CPM response can be the result of chronic pain, hence a possible bi-
directional relationship (40).  
There is a growing body of evidence suggesting that CPM may be an important biomarker of chronic 
pain and a predictor of treatment response (19). One may suggest that in patients with chronic pain and 
a dysfunctional CPM response, treatments with approaches that address the central nervous system 
mechanisms (e.g., pharmacological and cognitive) could be the first choice of treatment. Patients with 
chronic pain that demonstrate a dysfunctional CPM might also be particularly sensitive to interventions 
that help to reduce specific local nociceptive input (eg, physical medicine and manual treatment). 
However, standardization of CPM testing is lacking (29). 
Our study will use a structured CPM testing protocol to examine if the CPM responses are predictive of 
treatment outcomes after SMT and stretching exercises. 
Patient- reported outcome measures: 
Secondary measurements such as disability, quality of life and the subjective experience of chronic pain 
will also be evaluated, as this is important when considering chronic pain (41). These will be collected 
using the standard instruments described below: 
The neck disability index is an instrument designed to measure disability, and has been shown to be 
reliable and valid in Swedish (42). 
Pain intensity is measured with a validated NRS-11 scale where the subjects grades their perceived pain 
level using the anchors “no pain” and “worst possible pain”(23, 24). 
Measures of self-rated health is assessed by EQ-5D, a translated (Swedish) and validated questionnaire 
with five domains and three answer options in each (43, 44). 
To assess the affective quality of pain, the Swedish version of the short-form McGill pain questionnaire-2 
will be used. This is a validated questionnaire (27, 28) used in clinical trials designed to measure the 
subjective pain experience. 
These questionnaires will be given at baseline, and again at the 2nd and 3rd measurements.  In addition, 
they will be administered every other week the following 2 months after the study period has ended. 
Pain intensity (NRS-11) (23, 24) will be collected daily during the two week study period using text-
messages (SMS) and every other week the following 2 months using emailed questionnaires. 
The most common side-effects following SMT are local tenderness and tiredness of a short duration 
(17). In this study, the reactions to both treatment arms will be monitored using SMS sent to the 
participants one day after the first treatment.  

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Time line 
The data collection is expected to commence in January 2019 and to be finished within 12 months. 
Analysis 
Intention to treat analysis will be applied.  
Baseline variables might have direct effects on the outcomes and indirect effects via the mediating 
variables. To analyse the data, we therefore plan to use path analysis models with one or more 
mediators. As a complement, univariate multiple regression analysis (one outcome) and/or multivariate 
multiple regression analysis (more than one outcome) are planned.  
 
Possible interaction effects on the outcomes will be checked for. If they are statistically significant, 
group analyses will be considered. 
 
Ethical aspects 
SMT is applied clinically in musculoskeletal health care and has been examined in a variety of research 
studies. Serious complications are very rare (45, 46). The present study examines two commonly used 
treatment protocols in a clinical environment, which means that the subjects will not be subjected to a 
treatment that they would not normally receive when consulting for care. All test methods are well-
established procedures commonly used in research practice. If a subject experience an unexpected 
reaction to treatment or testing procedure, the subject will be taken out from the study by the research 
assistant, and undertake an individual treatment plan.  
 
The clinicians (chiropractors) who performs the treatments all have an academic degree, are licensed by 
the Swedish National Board of Health and Welfare (the national Patient Safety Act applies) and has a 
personal liability insurance through their professional federation (https://www.lkr.se/) (Nordic Insur-
ances). Thus, the subjects are insured in case of adverse events from treatment.  
 
When screening for eligibility, both written and verbal information about the purpose of the study, 
treatments, measurements and SMS procedures will be provided. At the study visit the patient will have 
an opportunity to ask the research clinician relevant questions, but will also be provided with a tele-
phone number where a part of the research group not involved in the data collection can answer all the 
questions they may have. All study subjects will sign informed consent forms before entering the trial. 

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Upon registration in the study, each subject will receive a subject identification number (ID), replacing 
personal identity number and name, which all measurement data and patient reported data will be 
linked to. The key that match the subject ID with personal identity number and name will be securely 
stored in a locked fireproof cabinet at Karolinska Institutet in accordance with the National Board of 
Health and Welfare's requirements for storage of journal documents.  
 
During the data collection, data are recorded and processed by the research clinicians, and all entries in 
the databases are recorded using the subject ID only. During the analyses, data will be completely 
anonymised and only the involved researchers will have access to the data, which will be stored 
electronically at Karolinska Institutet in accordance with local rules and European GDPR regulations. 
 
All reporting will be done at the group level without the possibility of identifying any individual study 
subjects. The results of the study will be published in open access journals, and will be communicated 
through several professional channels nationally and internationally. 
 
Central ethical approval has been confirmed from the Regional Ethical Review Board in Stockholm (ref 
approval no. 2018/2137-31) and has approved participation of all individual centres in the trial. 
 
Discussion 
The pain-reducing effects of SMT on certain spinal pain conditions are well established, as are the 
normal reactions to such treatment (5-7). However, the mechanisms behind these effects are not well 
understood, although it is hypothesized that the pain-reducing effects could be mediated through the 
ANS (12). Therefore, the study of HRV responses to SMT as part of a short treatment plan and its 
relation to pain sensitivity and normal reactions to treatment will advance the knowledge regarding the 
mechanisms involved in the specific effects of SMT. 
The development of CPM as a clinical prediction tool could potentially inform clinicians on what to 
expect in terms of treatment response concerning stretching and manual treatment. The knowledge 
gathered will inform future clinical studies regarding useful outcome measures, minimally clinically 
relevant change values, and necessary sample sizes in this type of research. 
There are some challenges to consider with the current design: The data collection demands effective 
recruitment to ensure sufficient number of subjects to adequately power the trial. As mentioned, the 
study will utilize an existing practise-based research network, where chiropractors have participated and 
successfully recruited patients in previous studies, thus we believe that it is feasible to include the 
required number of subjects. 
Based on previous experience with multi-centre clinical trials, procedures are in place to minimize the 
burden on the subjects in the study. However, attrition is to be expected to some degree. Reminder-

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functions in the email and text-message measurement protocols have been included, some of which are 
automatic, but some will require monitoring and individual follow up. As subjects deal with only one 
research clinician and one treating clinician, we believe that the personal contact will be optimal, thus 
reducing attrition. 
The testing methods require a highly structured testing protocol as the testing equipment is highly 
sensitive. However, we believe that this is achievable considering the experience of the research group 
members. 
A pilot study will be conducted prior to commencing the full-scale study. If procedures, recruiting or 
monitoring are found to be unfeasible, relevant changes to the protocol will be made. The record at 
Clinical Trials will be revised accordingly, the funder will be notified, and a study protocol update will be 
submitted as an erratum. 
Trial status 
Patient recruitment will begin in January 2019, and is expected to be completed by December 2019. 
 
Abbreviations 
NP: Neck Pain 
NRS-11: Numerical rating scale (11 steps, 0–10) 
ANS: Autonomic Nervous System 
SMT: Spinal Manipulative Therapy 
CMP: Conditioned Pain Modulation 
HRV: Heart Rate Variability 
HVLA: High Velocity, Low Amplitude 
MOB: Spinal Mobilization 
 
Declerations 
 
Ethics approval and consent to participate 
All study subjects will sign informed consent forms before entering the trial. 
Availability of data and material 

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All collected data will be stored for at least 10 years and can only be identified by code number. Only 
researchers who are directly involved in the project will have access to the material. Anonymized 
information may be shared with other researchers upon request, pending ethical approval.  
 
 
Competing interests 
None of the authors have any competing interests to disclose. None of the funding bodies are involved 
in or have influence over the design of the study, the interpretation of the results, or the decision to 
publish the results. 
 
 
Trial modifications 
Will be recorded in clinicaltrials.gov 
 
Authors’ contributions 
AB, IA and AE instigated this study, drafted the first version of the manuscript and are part of the project 
management group. IA and AE were involved in the management and supervision of the trial. SO’N is 
involved in the project design and testing protocol. All authors have been involved in the planning and 
design of the study as well as critical revision and intellectual improvement of the manuscript. All 
authors have read and approved the final manuscript. 
 
Authors’ information 
AB is a part-time clinically active chiropractor in private practice and is a PhD student at Karolinska 
Institutet funded by the Institute for Chiropractic and Neuro-musculoskeletal Research (IKoN). 
IA is an associate professor in musculoskeletal health at Karolinska Institutet, and research leader of the 
Norwegian Chiropractic Research Foundation (ELIB) 
AE is a part-time clinically active chiropractor in private practice and has a post-doctoral position at 
Karolinska Institutet funded by the European Centre for Chiropractic Research Excellence (ECCRE) and 
Karolinska Institutet. 
SO’N is employed as an associate clinical professor at IRS, University of Southern Denmark and also 
works as a Chiropractor at the Spine Centre of Southern Denmark, Lillebaelt Hospital. He is funded partly 
by a tenure position (Uni. Southern Denmark), partly by external post-doc grants. 
 
Acknowledgements 

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We have received valuable input into the study design from Mathieu Picchiottino, DC, MSc (Master of 
Science), PhD student., Margaux Honoré, DC, MSc (Master of Science), PhD student., Charlotte Leboeuf-
Yde, MPH, PhD, Professor., Audun Stubhaug MD, DMedSci., Professor, David Hallman, PhD. and Jan 
Hagberg PhD, statistician 
 
Consent for publication 
Not applicable 
 
Data monitoring  
Participants are not exposed to any excess risk because of participating in this trial. We did therefore not 
deem it necessary to have a data monitoring committee or an external audit.  
 
Funding 
The study is funded by the Institute of Chiropractic and Neuro-musculoskeletal Research (IKON in 
Swedish). The funding body had no influence over the design of the study, and will not have any 
influence over the data-collection, analysis or reporting of results.  
Contact information:  
IKON, LKR Service AB, c/o Företagarna, S- 106 67 Stockholm 
070-6891179. Forskningsfonden@lkr.se 
 
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