Effectiveness of an osteopathic treatment on the autonomic nervous system: a systematic review of the literature

Objective The objective of this systematic review was to evaluate the effectiveness of an osteopathic treatment on the autonomic nervous system (ANS). For this purpose, published primary studies were analysed and critically evaluated. Method To generate this review, 15 electronic databases were systematically searched for studies. Randomized clinical controlled trials (RCT) and clinical controlled trials (CCT) are included in the review and evaluated with appropriate assessment tools (Downs and Black Checklist and the checklist from Kienle and Kiene). Results 23 published studies (10 RCT, 1 clinic multi-centre study, 1 CCT, 5 randomized cross-over studies, 5 randomized pilot studies and 1 single case study) are included in this review. The studies were evaluated with the assessment tools according to their quality. 3 studies are graded as high quality, 11 as moderate and 8 as low-quality studies. Conclusion The included published studies represent a good level of evidence. Due to a small number of subjects and no follow-ups, the methodological quality is rated as moderate. A significant change on the ANS was shown in studies including High-Velocity Low-Amplitude Techniques (HVLAT). No statement could be drawn in studies in which they used cranial osteopathic techniques due to the lack of methodological quality. A significant change on the ANS is shown in the treatment of the suboccipital region. In studies which evaluated the effectiveness of mobilization in the cervical and thoracic region, no statement could be displayed due to a low level of evidence. None of the findings in these studies have given statements if ANS activation takes place in the sympathetic or parasympathetic system.


Background
The osteopathic health care with its philosophy and principles of practice is a holistic, person-centred treatment concept with body structure (anatomy) and body function (physiology) as a unit [1].
The osteopathic treatment principles are integrated in the five osteopathic treatment models which are categorized as followed: postural-biomechanical model, respiratory-circulatory model, bioenergetic-metabolic model, biopsychosocial model and neurologic-anatomic model [2].
The treatment of the autonomic nervous system (ANS) is an important sequence of the treatment procedures as it is involved in the regulation of the homoeostasis of the body functions, e.g. cardiovascular system, blood pressure, temperature [3]. Therefore, a good function of the innervations from the 1st centre of the ANS to the target organ is required [3]. Imbalances between the sympathetic and parasympathetic over a longer period of time can lead to various symptoms in the body. It has an influence on, e.g. the vasoconstriction of the blood vessels in the gastro-intestinal region, vasodilatation in the skeletal muscles, low or high heart rate, changes in the secretion of glands, changes in the bronchial muscles and glands which can be revealed by the body as a malfunction of an organ [4].
A wide variety of manual treatment techniques is used by osteopaths to improve the physiological functions in the body and to regain homoeostasis which has been altered by somatic dysfunction [5]. Osteopathic manipulation techniques are defined as followed: thrust manipulation techniques (High-Velocity Low-Amplitude Thrust), soft tissue techniques (myofascial release techniques), Counterstrain techniques, Balanced Ligamentous Tension and Ligamentous Articular Strain techniques, visceral techniques, osteopathic craniosacral techniques [1].
Welch and Boone [6] reported in their study in 2008 that cervical and thoracic manipulation techniques influence the activity of the ANS. A rib raise technique, which Henderson et al. [7] discovered in their study, also has an influence on the ANS activity. Other osteopathic treatment techniques such as craniosacral compression techniques on the fourth ventricle of the brain also show a change in the ANS activity which Curi et al. [8] studied in 2017.
Unfortunately, the number of studies done in this field displays indifferent results in the change of the ANS activity.
The aim of the current review is to evaluate with the existing literature, if an osteopathic treatment affects the autonomic nervous system and if a certain treatment in different body regions has an effect on the sympathetic or parasympathetic nervous system and can lead to changes in different malfunctions in the body system as mentioned above. Study search was restricted by language barriers (only English, German) due to the writer's language limitations.

Methods and materials
A comprehensive search of the existing literature was undertaken to identify published original research examining the effectiveness of treatments to the ANS. In accordance with the PRISMA statement, the review techniques in this study followed their standards [9]. The included studies for this review were carried out from researchers all over the world, e.g. Australia, Brazil, Canada, France, Italy, Japan, Malaysia, New Zealand, Spain, UK, USA.

Inclusion criteria
There were no time limits set for the research of the literature.

Types of studies
The present systematic review included randomized clinical controlled trials (RCT), clinical controlled trials (CCT), single case studies, multi-centre studies, pilot studies and observational studies.
Types of interventions All studies in the field of osteopathic manipulative treatments (OMT), physiotherapy, chiropractic, manual medicine were included in the search strategy. Some treatment techniques in these professional groups overlap, which is why they were all included in the search.

Exclusion criteria
Articles were excluded if they were not written in English or German, did not present original empirical data or only an abstract was available or if they only represented active physiotherapy in the study. Also excluded were articles in which OMT was combined with other therapy forms. Conference proceedings, editorials, letters or seminar dossiers were excluded too.

Outcomes
The primary outcome was to estimate the efficacy or effectiveness of an osteopathic treatment on the ANS. As a second outcome, the effect of treatment techniques in different body regions for sympathetic and parasympathetic nervous system was evaluated. Any kind of an adverse event was a second outcome.
The following search terms, defined by MeSH (Medical subject headings), were used: osteopathic medicine (OM), autonomic nervous system (ANS), parasympathetic nervous system (PNS), sympathetic nervous system (SNS), musculoskeletal manipulations, chiropractic, therapy/therapeutic use, manual therapy, mobilization. The search was supplemented by a manual search in the reference list for all relevant studies that were not listed when searching the electronic databases and by citation tracking of the identified trials. The author of this review systematically  screened the titles and abstracts of the results from the  search strategy (1st selection). Potential studies were read in full text and once more evaluated for the inclusion in the current review (2nd selection).

Study selection
Data extraction Data were extracted by the author of the current review. For the purpose of this review, the information extracted from the included papers were author, source, and design, characteristics of the participants/aim of the study, sample, intervention, and summary of findings.
Dealing with missing data If the article did not contain sufficient information or was not completed, the authors were contacted for additional information or the full article.
Quality assessment The summary of results was reported following the PRISMA statement [9].
The quality of evidence for each outcome in the included studies was assessed using the Downs and Black scale [10] for RCT, non-RCT studies, and for the single case studies, the checklist from Kienle and Kiene was used [11].
The Downs and Black scale is based on a checklist of 27 items and has been found to be valid for critically evaluating RCT and non-RCT studies [10]. The checklist included four categories for evaluation: reporting, external validity, internal validity/bias, internal validity/confounding. The Downs and Black scale specifies 4 levels of quality using this scoring system which is categorized as followed in Table 1: strong, moderate, limited or poor quality [12].
The checklist from Kienle and Kiene was developed to evaluate the methodological quality of single case studies, case series [11]. It consists of 11 items which are scored with zero or one point. The quality index of the scoring system is categorized with good, moderate or poor as shown in Table 2.

Included studies
Electronic search identified 2166 papers (see Fig. 1). In the first selection process after screening title and abstracts, 114 studies were left (1st selection, including duplicates). In the next step, 73 duplicates were removed. After reading the full text of 41 papers and applying the predefined inclusion criteria, 23 articles were left for the qualitative analysing (2nd selection).

Excluded studies
In the first selection process, 73 duplicates were excluded and from the 41 papers read in full text, 18 were excluded for various reasons.
The results of the quality of the included studies scaled with the Downs and Black checklist are listed in Table 3. The single case study [25], evaluated with the checklist from Kienle and Kiene [11], scored 7 points and the result on the quality index was moderate.
The studied population ranged in size from 1 in the single case study [25] and 10 in a pilot study [16] to 539 in a clinical multi-centre study [22]. Treatment  A wide range of measurements can be used to demonstrate changes in the ANS through heart rate variability (HRV) [14,15,23] (quantitative marker for changes in the vegetative nervous system [33]), heart frequency, blood pressure [23], breathing rate [17], edge light pupil effect [32], distal skin conductance/skin temperature [20,21,25], and also through changes in the immune [24] and endocrine system [6,7].
The participants in the study groups were healthy adults or patients with pain in the body region that was tested in the study.
The subject groups in the included articles for this review were very heterogeneous and therefore, no statistical analysis of the study results was possible in this review. Table 4 provides a summary of the characteristics of each study, including treatment sessions and interventions.

Discussion
The general quality of the selected articles was good including a lot of RCTs. This is why the author concluded that overall there is a positive result towards the question if an osteopathic treatment can influence the ANS.
As the treatment techniques and the treated body regions in the included studies vary a lot, the included studies were summarized in groups for the discussion. Therefore, the heterogeneity of the articles does not allow for a statistical analysis.

High-velocity low-amplitude techniques (HVLAT) in the cervical spine
Six included articles [6,21,22,24,31,32] investigated the effects of HVLAT techniques in the cervical spine on the ANS. Techniques in the upper and lower cervical spine in one article [21], which is categorized as strong in the Downs and Black checklist [10] and including 30 subjects show statistical changes in the ANS. Findings in another article [31] are that techniques in the upper cervical region on 25 healthy subjects expose significant changes in the ANS. In a randomized cross-over design study [24], which was assessed in limited methodological quality, changes were measured in the ANS through sympathetic relaxation. Inconsistent results are shown in one article [6], because their measurement tool varies (HRV, blood pressure, pulse rate). Only 7 out of 40 were measured with HRV, which qualifies as the gold standard. Their results show an increased parasympathetic activity in cervical techniques and sympathetic in thoracic techniques. In the randomized pilot study [32], changes in the ANS through techniques in the upper cervical region on 13 subjects were measured by use of the edge light pupil cycle time. This study points at a low level of evidence and was categorized as limited in their methodological quality. In a multisite clinical study [22], 539 subjects with cervical and lumbar pain and headache were measured with HRV after a HVLAT technique in the pain region. Despite a moderate categorization in the methodological quality, there are significant changes in the ANS measured.
Although the studies were limited regarding number of subjects, methodological quality and level of evidence, there is a significant change in the ANS in all publications. Almost all used HRV as a measurement instrument. No valid statement is possible if sympathetic or parasympathetic is more influenced by HVLAT techniques in the upper or lower cervical spine.

HVLAT in the lumbar region
2 studies included [20,23] investigated the effects of HVLAT techniques in the lumbar spine. In one study        [23], the effect with 22 subjects with acute low back pain was measured through a significant change in the modulation of the ANS. In another article [20] with a good level of evidence and a moderate categorization in the methodological quality, the effect of a HVLAT technique on L5 shows a significant change in the parasympathetic activity.
In addition in a single case study [25], there were also changes in the ANS after using a HVLAT technique on the lumbar spine.
In an article [8], they measured changes by means of HRV and blood pressure in 30 subjects, half of them were normotensive and the other half hypertensive, with a cranial technique named CV4. The results showed a significant change in the parasympathetic activity. No follow-up was taken and no conclusion for a parasympathetic long-term effect with hypertension is possible. In one RCT [18], they compared the effect of a cranial CV4 technique and a placebo in 40 subjects. Measurement is taken with plasmatic catecholamine levels, blood pressure and heart rate. No effects related to the intervention were found. Another study [17] measured the effect of a cranial osteopathic technique by the use of HRV and cerebral tissue oxygen saturation in healthy subjects. The results show an effect in both measurement tools and therefore changes in the ANS. In an article [30] with 25 subjects, they measured the blood flow in the finger after a gentle soft tissue manipulation in the suboccipital region. Results show a slight reduction of the sympathetic activity. The level of evidence is low and the methodological quality is moderate, so the results have to be interpreted with care. In a randomized cross-over design [29], it was studied if a so-called suboccipital decompression and a soft tissue technique in this region on 19 subjects influence the parasympathethic system and the N. Vagus measured by HRV. Results show a significant change in the ANS. The methodological quality is limited and the number of participants is small which lowers the evaluation. In a pilot study [14], 20 subjects were treated with craniosacral techniques after an acute stressor. Changes were measured by HRV and cortisol level samples in saliva. The results show a reduction on the ANS and a prevention of the increase in the cortisol level. A pilot study [16] compared the effects of a craniosacral CV4 technique and a placebo therapy. The results on 10 subjects showed a very low impact on the ANS. In a pilot study [15] it was measured, if a HVLAT in the thoracic spine region or a craniosacrale CV4 technique shows more changes in the ANS. The results show that a CV4 technique influences sympathovagal balance and the HVLAT reduces the sympathetic system.
According to all the results in these studies, there is a tendency to a positive change in the ANS. A significant change was not reported. Only techniques in the suboccipital region showed significant changes in the ANS.

Mobilization techniques in the thoracic and cervical spine
In 4 studies [19,[26][27][28], the influence of mobilization techniques in thoracic or cervical spine areas on the ANS measured through changes in the upper extremity was examined. Results of this investigations show that there is an alteration in the vegetative nervous system. No valid statement is possible if it is in the 1st, 2nd, or 3rd centre of the ANS. An RCT study [19] measured the effect of an anterior/posterior mobilization of the upper cervical spine on the pain reduction in the craniofascial region and on the TMD. The pain reduction is related to changes in the sympathetic nervous system. The study has a good level of evidence. In another RCT [28], they investigated the effect of a posterior/anterior rotation mobilization in the thoracic spine. Significant changes in the sympathetic nervous system were measured in the hands. The level of evidence of this study is good and the methodological quality was rated moderate. In one article [26], they measured the effect of mobilization of the vertebra C5 on the sympathetic function of the upper extremity. The results show a significant increase in the skin conductance. The results are limited as the methodological quality is poor and the number of probands is only 16. The effect of posterior/anterior mobilization in the cervical spine with 0.5 Hz or 2 Hz on the sympathetic function of the upper extremity was investigated in an RCT [27]. The result shows a change in the skin conductance which means an increase in the efferent sympathetic activity. Considering the outcomes of the study, it has to be said that the results of the measurement parameters are very inconsistent.
Two [7,13] additional studies, which were not summarized in one of the groups above, are discussed in the following text paragraph.
In an RCT [13], they investigated the effect of an osteopathic treatment on 66 subjects with placebo and control group measured by HRV. Results show a statistical significant change in the ANS.
In a randomized pilot study [7], the effect of a rib raise technique on the ANS and the hypothalamicpituitary-adrenal axis using non-invasive biomarkers was investigated. The results suggest that there is a