Table 4 Main characteristics of included studies

Ruffini et al. [13]

Frontiers in Neuroscience

RCT

Effect of an OMT in healthy subjects compared to control group and sham therapy measured with variations of high-frequency (HF) parameter of HRV (2 × a week);

n = 66

Two therapies for 25 min (10 min evaluation; 15 min patient need-based OMT)

Group A: OMT + sham therapy

Group B: sham therapy + OMT

Group C: 2× no intervention

Statistic sign. difference in the groups in HF (primary outcome measure p < 0.001) and HRV outcome measures.

No difference in sham therapy and in Group C with no intervention

Fornari [14]

JAOA

Randomized pilot study

To explore the modulating effect of cranial OMT on healthy young men on autonomic neural regulation measured with HRV and to verify its ability to influence the activity of the hypothalamic–pituitary–adrenocortical axis (measured with saliva samples)

n  = 20

Immediate cranial OMT after an acute 5-min mental stress episode for the intervention group; control group received sham therapy with light touch

Statistic sign. reduction of chronotrop effect with OMT after an acute stressor (t = − 2.9, p < 0.05) and modulation of sympathovagal balance towards sympathetic activity (t = − 2.8, p < 0.05); lower cortisol level after acute mental stressor in intervention group (t = − 2.3, p < 0.05)

La Touche et al. [19]

The Clinical Journal of Pain

RCT

The aims were to investigate the effects of an anterior-posterior upper cervical mobilization on pain modulation in craniofacial and cervical regions and its influence on the sympathetic nervous system

n  = 32

Anterior–posterior mobilization (C0–C3) with 0.5 Hz, 3 intervals with 2 min each, 30-s pause in between;

Control group received sham therapy

Increased pressure pain thresholds in the craniofacial and cervical regions in intervention group (p < 0.001), and decrease in pain intensity in the intervention group compared with placebo (p < 0.001). A change in the sympathetic nervous system is due to pain relief

Petersen et al. [26]

Physiotherapy Theory and Practice

RCT

The aim of this study was to evaluate the effect of a commonly utilised cervical mobilization technique on sympathetic function in the upper limb of normal pain-free volunteers

n  = 16

Each participant was in the intervention, control and placebo group.

Duration: 3 times 1 min on the vertebra C5 (grade III)

The mobilization (grade III) with healthy subjects stimulates the periphery sympathetic nervous system and increases the skin conductance (50–60%) (p < 0.05); no statistical change in skin temperature (p = 0.10)

Jowsey and Perry [28]

Manual Therapy

RCT

This study investigated whether a grade III posterior-anterior rotator joint mobilization technique applied on T4 vertebra at a frequency of 0.5 Hz had demonstrably greater effects than placebo intervention on skin conductance in the hands of healthy subjects

n  = 36

Intervertebral grade III p/a rotator mobilization 3 × 1 min

A grade III p/a rotator mobilization technique shows a side-specific increase in the sympathetic activity in the right hand (F = 4.888, df = 35, p = 0.034).

Giles et al. [29]

The Journal of Alternative and Complementary Medicine

Randomized cross-over design

The study was designed to determine the acute effect of upper cervical spine manipulation (soft tissue techniques and sub occipital decompression) in healthy subjects on the ANS measured by HRV

n  = 19

Each participant acts as its own intervention, control and placebo group; Duration of therapy: 15 min

The results show a modulation in the parasympathetic HRV measurements and a shift to sympathovagal balance.

Increase in the SDNN interval (p < 0.01); increase in the HF in spectral power (p = 0.03)

Decrease in LF/HF ratio (p = 0.01)

Scoppa et al. [15]

Acta Medica Mediterranea

Randomized pilot study

The purpose of this pilot study with healthy subjects was twofold:

Compare different OMTs that supposedly interact either with ortho- or para-sympathetic branches of the ANS

Ascertain whether there is a relationship between autonomic Balance and Quiet Upright Stance Balance

n  = 51

randomized to different groups

HVLAT on the dorsal spine or CV4 technique (10 min);

Time measurement: immediate after OMT, after 20 min, after 100 min, after 280 min; balance test with each measurement

Immediate reduction in ANS after HVLAT. After CV technique delayed response in the ANS. Both treatments have an influence on the quiet upright stance balance

Purdy et al. [30]

JAOA

Randomized Cross-over design

Evaluation of the effect of a soft tissue technique in the suboccipital region measured by blood flow in the finger as a marker for the sympathetic nervous system change

n  = 25

Each subject was in intervention (A) and sham (B) group. 120-s treatment either A or B; 10-min Pause, then the other treatment

All groups had sign. changes in the measurement with OMT. As a conclusion, there is a sign. reduction in the sympathetic nervous system activity in group A (change in X: p = 0.01, Y: p < 0.001) and B (change in X: p = 0.0014, Y: p = < 0.0001). No change was with subjects who felt uncomfortable with the treatment

Milnes and Moran [16]

International Journal of Osteopathic Medicine

Pilot study

The aim of this study was to investigate the physiological effects in healthy subjects resulting from the administration of a single cranial technique (CV4) compared with simple touch

n  = 10

Design with repeated measurements; Each subject acts in intervention and placebo group. 5-min touch only (placebo), CV4 treatment according to patients’ need

No statistic difference is shown in skin temperature and HRV with ANOVA

Constant breath frequency in all 5 phases MW: 14.12 (SD 3.2)

Concluding to the results, there is only a minimal physiological effect with a CV4 technique on the ANS. There might be “responder” and “non-responder” for cranial OMT.

Shi et al. [17]

JAOA

randomized Cross-over design

The aim of this study is to examine the effects of cranial OMT on cerebral tissue oxygen saturation (SctO2) and the ANS in healthy adults

n  = 21

Each subject acts in intervention and placebo group. 2 cranial OMT techniques (augmentation and suppression) each for 4 min

Statistical sign. reduction of the SctO2 during OMT (left: p = 0.026, right: p = 0.007) suppression technique and through this a balance in the ANS. No effects with augmentation or placebo.

Decrease in LF and increase in HF (p = 0.05)

Cardoso-de-Mello-e-Mello-Ribeiro [18]

Evidence-Based Complementary and Alternative Medicine

RCT

This study aimed at evaluating the effects of a CV4 compression technique on the ANS

n  = 40

Intervention group received CV4 technique for 10 min; placebo group: bilateral non-therapeutic contact on the occipital bone for 10 min

CV4 compression technique seems not to have any effect in plasmatic catecholamine levels, blood pressure or heart rate. No sign. change in the comparison of pre- or post-intervention results in all study groups (p < 0.01)

Curi et al. [8]

Journal of Bodywork and Movement Therapies

RCT

The aim of this study was to compare blood pressure and HRV amongst hypertensive stage I (HT) and normotensive (NT) individuals who were submitted to cranial CV4 technique

n  = 30

CV4 technique was applied to both groups. Measurements were taken immediate after technique, 5, 10 and 15 min after intervention

Blood pressure reduction in HT group, statistical sign. changes in sympathovagal tension after 15 min (measured with SDNN: p = 0.01) in both groups. RMSSD measure changes in the HT group pre- and post-intervention (p = 0.01)

The data showed a change in the sympathovagal balance.

Chiu and Wright [27]

Manual Therapy

RCT

The aim of this study was to compare the effects of different rates of application of two different rates (2 Hz or 0.5 Hz) of a C5 grade III central posterior–anterior mobilization technique on skin conductance and skin temperature on sympathetic function in normal pain-free volunteers

n  = 16

Treatment applied on 3 successive days. Randomized intervention group 1 (2 Hz) or intervention group 2 (0.5 Hz) or placebo each for 1 min

There is a sign. change in the SC between group 1 and 2 and a sign. effect in the ST in all 3 groups.

The mobilization grade III with 2 Hz shows an increase in SC (50–60%) and an increase in efferent sympathetic activity.

Roy et al. [20]

Journal of Manipulative and Physiological Therapeutics

RCT

The purpose of this study was to examine the HRV in the presence of absence of pain in the lower back, whilst receiving one chiropractic treatment at L5 from either a manually assisted mechanical force (Activator) or a traditional HVLAT

n  = 51

Intervention group 1: thrust with Activator, sham group 1: contact only with Activator, Intervention group 2: HVLAT on L5 (subject with pain), sham group 2: only lumbar roll position, no thrust;

Control group: no intervention

In all groups except in the control group, the HRV was decreased.

There is a change in the parasympathetic activity after a HVLAT or Activator technique in the lumbar region. Group differences in HRV modulation depend on subjects with or without pain

Win et al. [21]

Journal of Chiropractic Medicine

RCT

The aims of this study were to examine ANS response by HRV hemodynamic parameters and numeric pain scale when either upper (C1 and C2) or lower (C6 and C7) cervical segments were manipulated in healthy subjects or in patients with acute neck pain

n  = 30

Week 1: data collection; Week 2: randomized to upper or lower cervical intervention; Week 3: other missing cervical intervention

According to the statistical changes in HRV parameters, there is a change in the parasympathetic system after intervention of the upper cervical spine (increase in SDNN: p = 0.02) and a change in the sympathetic system after invention in the lower cervical spine (decrease in systolic BP p = 0.002). A dominant parasympathetic activity is shown in patients with acute neck pain in the upper and lower cervical spine.

Zhang et al. [27]

Journal of Manipulative and Physiological Therapeutics

Clinical multi-centre study

The purpose of this study is to investigate the effect of a 4-week chiropractic care in a multiclinic setting on ANS activities using HRV with patients suffering from lumbar or neck pain or headache

Data collection from 96 therapists;

n  = 539

Intervention: in 4 weeks, 1 chiropractic treatment once a week; placebo: no intervention

Statistic sign. change in HRV (SDNN, VLF, total power, LF: P < 0.05) after 1 chiropractic treatment. After 4 weeks, there is also a change in HRV due to a change in ANS activity.

Budgell and Hirano [31]

Autonomic Neuroscience

Randomized Cross-over design

Effects of a cervical HVLAT technique (C1–C2) on HRV in healthy subjects with a 1-week pause in between intervention and placebo

n  = 25

Randomized allocation in which week intervention or placebo takes place

Intervention group showed a sign. change in HRV parameters (absolute LF: p = 0.916, normal LF: p = 0.0061, LF/HF ratio: p = 0.0037) which may reflect a shift in balance between sympathetic and parasympathetic output to the heart.

Younes et al. [23]

Chiropractic & Manual Therapies

RCT

The study aimed to quantify the effect of an OMT at patients with acute back pain on the parasympathetic autonomic control measured with HRV, baroreflex, systolic blood pressure

n  = 22

45-min intervention: HVLAT, lumbar mobilization, deep massage, Strain–Counterstrain techniques, MET, ischaemic pressure massage. 2 times (1st and 7th day)

Sign. increase in IG: RMSSD (p = 0.003), HF (p = 0.005)

Baroreflex sensitivity in HF-band higher in IG than in CG (p < 0.001)

A vagal modulation of the HRV in the intervention group took place.

Welch and Boone [6]

Journal of Chiropractic Medicine

CCT

The aim of this study was to measure the effect of a cervical or thoracic HVLAT technique in healthy subjects on the ANS measured with blood pressure, pulse rate and HRV

n  = 40

2 times HVLAT intervention (cervical and thoracic spine)

A sign. parasympathetic activity after cervical HVLAT (decrease of diastolic BP: P = 0.038, moderate clinical effect (0.50), increase in pulse rate: P = 0.044) and a sign. sympathetic activity after thoracic HVALT intervention.

Unfortunately, HRV was measured only with few patients.

Fukada et al. [24]

Alternative Therapies

Cross-over design

Investigation of cerebral metabolic changes after a chiropractic spinal manipulation in subjects with cervical pain and neck stiffness measured with FDG-PET

n  = 15

Intervention group: cervical manipulation with Activator and PET scan, placebo: group PET scan only.

There is a sympathetic relaxation and pain reduction after spinal manipulation because of a change in the cerebral glucose metabolism (P < 0.001)

Henderson et al. [7]

JAOA

Randomized pilot study

Effects of a rib raise technique on the ANS and the hypothalamic–pituitary–adrenal axis with healthy subjects measured with salivary flow rate, Alpha amylase activity and cortisol level

n  = 23

Intervention or sham therapy

Rib raise technique decreases the sympathetic activity (immediate reduction in salivary alpha amylase activity (p = 0.014) and 10 min after (p = 0.008)), but there is no influence on the hypothalamic–pituitary–adrenal axis because there is no change in parasympathetic activity.

Gibbons et al. [32]

Journal of Manipulative and Physiological Therapeutics

Randomized pilot study

The aim of this study was to investigate a HVLAT technique in the cervical spine (C1 + C2) and their effects on the ANS measured by ELPCT (edge light pupil cycle time) in healthy subjects

n  = 13

Randomized assignment if HVLAT rotator component was to the right or left. No control group

Sign. change in ELPCT before and after HVLAT in both eyes (p = 0.002)

There is a change in the ANS after HVLAT technique in the cervical spine because the ELPCT is mediated through the ANS.

Driscoll and Hall [25]

Journal of Manipulative and Physiological Therapeutics

Single case study

The aim of this study was to evaluate if there is a change in the ANS and cardiovascular system after chiropractic HVLAT technique in the symptomatic regions of the spine measured with blood pressure, pulse rate and ECG

n  = 1

10 treatments in 5 weeks

There was a change in parasympathetic and sympathetic HRV measures in different treatments. No sign. change in the measurements of the diastolic and systolic blood pressure.