Abstract
Background:
Spine pain conditions, such as low back pain (LBP) and neck pain, are prevalent musculoskeletal disorders. The autonomic nervous system (ANS) has been implicated as a potential contributor to pain. However, research investigating the impact of physiotherapy interventions on ANS function in patients with spinal pain disorders remains limited.
Objective:
This review aims to examine the influence of physiotherapy interventions on the ANS in patients with spinal pain conditions.
Methods:
A comprehensive literature search was conducted in PubMed, CINAHL, Web of Science, Ovid, and the Cochrane Controlled Trials Register to identify eligible randomized clinical trials. For meta-analysis, a random-effects model was used to compare the effects of physiotherapy interventions on ANS outcomes to comparison interventions.
Results:
A total of 16 studies were included in the systematic review, of which 11 were eligible for meta-analysis. Nine studies focused on participants with LBP, while seven studies focused on neck pain. The included studies investigated a variety of physiotherapy interventions compared to various control interventions. The meta-analysis revealed no statistically significant difference in ANS-related parameters between physiotherapy and comparison groups for LBP (pooled standardized mean difference [SMD] = 0.12; 95% CI: −0.10, 0.32; I2 = 55%) or neck pain (SMD = 0.09; 95% CI: – 0.29, 0.46; I2 = 74%).
Conclusions:
This systematic review and meta-analysis found no evidence that physiotherapy interventions induce ANS modulation compared to other interventions.
Funding:
None
Registration:
PROSPERO (registration no.: CRD42023460760)
Keywords: Heart rate variability, low back pain, neck pain, parasympathetic, physical therapy, sympathetic
INTRODUCTION
The autonomic nervous system (ANS) is intricately involved in pain modulation, influencing both peripheral and central nervous system responses to noxious stimuli. Nociceptive pathways, which transmit pain signals, interact with ANS mechanisms.[1] Notably, brain regions such as the anterior cingulate cortex and periaqueductal gray, implicated in both autonomic regulation and pain processing, underscore the overlap between these systems.[2] Heart rate variability (HRV), a measure of autonomic function, exhibits changes during pain experiences that correlate with altered functional connectivity in these brain regions.[2] This complex interplay between the ANS and pain processing highlights its potential as a target for innovative pain management strategies. The risk of spine pain is influenced by a combination of physical, socioeconomic, general health, and psychological factors, which are often interconnected.[3] The diversity of treatment options reflects the varied underlying pain mechanisms, including nociceptive, neuropathic, and autonomic pain.[4] Understanding these mechanisms is essential for developing effective pain management strategies.[5]
Physiotherapy plays a vital role in the management of chronic spine pain to alleviate symptoms and improve quality of life.[5] A meta-regression analysis found that exercise modulates ANS and HRV in healthy adults and patients with stroke, hypertension, and diabetes mellites, both during and after physical activity.[6] Few clinical studies have also examined the effect of different physiotherapy techniques on the function of ANS in patients with musculoskeletal conditions.[7,8,9] Manual therapy targets neurophysiological pathways by modulating afferent signaling to the central autonomic network,[10] while exercise interventions stimulate vagal activation to restore parasympathetic tone.[11] Furthermore, physiotherapy integrates stress-regulation strategies, such as controlled breathing, to refine autonomic responsiveness.[12] Within this integrated framework, HRV serves a dual role: it functions as a mechanistic mediator of immediate autonomic shifts and as a biomarker of recovery, indexing the systemic adaptations associated with pain reduction and functional improvement.[13]
Spinal pain syndromes, particularly low back pain (LBP), are a significant global concern. A 2023 study estimated that approximately 619 million people worldwide experience LBP at any given time. Despite the high prevalence and impact, managing spinal pain syndromes remains challenging in terms of their diagnosis and treatment.[14] Developing more effective and targeted treatments for spinal pain, particularly chronic, is essential. To our knowledge, no systematic review has examined the impact of physiotherapy interventions on autonomic pain mechanisms in individuals with spinal conditions. This systematic review aimed to investigate the effects of physiotherapy on the function of ANS in patients with spinal pain disorders.
METHODS
Protocol and registration
This review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines.[15] The protocol was registered on the PROSPERO (registration no.: CRD42023460760).
Search strategy
Two reviewers (H.A.A. and H.A.) searched multiple electronic databases, including PubMed, CINAHL, Web of Science, Ovid, and the Cochrane Controlled Trials Register from inception to the date of last search (i.e. November 16, 2024). The reviewers developed a focused research question using the PICO framework. Keywords were meticulously identified and categorized into four distinct groups. The first group was spine pain conditions, such as neck pain, thoracic pain, and LBP. The second group was physiotherapy interventions, such as manual therapy, electrotherapy, and therapeutic exercises. The third group was HRV parameters, which reflect ANS measures [Supplementary Table 1], including parasympathetic and sympathetic nervous system function.[16] The fourth group was focused on the comparison with the intervention, the effect of any conservative treatment or sham. A librarian was consulted to refine the keyword search strategy, ensuring effective use of wildcard and truncation symbols to maximize the breadth and precision of the literature search [Supplementary Table 2]. Additionally, a manual search of reference lists from relevant studies was conducted to identify any additional studies that may not have been indexed in the electronic databases.
Supplementary Table 1.
Parameters of heart rate variability
| Parameters | Explanation |
|---|---|
| HR | Heart rate. It is the number of times the heart beats per minute. It indicates overall cardiovascular health and fitness level |
| RMSSD | Root mean square of successive differences. It is a measure of short-term variability in HR, indicating parasympathetic activity. It is used to assess PNS activity |
| TP | Total power. It is the total variance in HRV over a specific period, reflecting overall autonomic activity. It indicates the total ANS activity |
| LF | Low frequency. It is a component of HRV associated with both sympathetic and parasympathetic activity, typically measured in the 0.04–0.15 Hz range. It reflects a mix of sympathetic and parasympathetic influence on HR |
| HF | High frequency. It is a component of HRV primarily associated with parasympathetic activity, typically measured in the 0.15–0.4 Hz range. It indicates PNS activity |
| LF/HF Ratio | Low frequency to high frequency ratio. It is the ratio of LF to HF, indicating the balance between the two branches of ANS. It is used to assess the balance between SNS and PNS activity; a higher ratio typically indicates a shift toward sympathetic dominance (stress/arousal), whereas a lower ratio suggests parasympathetic dominance (recovery/rest) |
| RR | Duration between two consecutive heartbeats. It is the time interval between two successive R-waves in the electrocardiogram. It indicates HRV and rhythm regularity |
| VLF | Very low frequency. It is a component of HRV associated with long-term regulatory mechanisms, typically measured in the 0.0033–0.04 Hz range. It reflects long-term autonomic regulation and other physiological processes |
| Nn50 | Number of times per hour that the difference between two consecutive RR intervals exceeds 50 ms. It is a count of the number of successive RR intervals that differ by more than 50 ms. It is used to assess PNS activity |
| Pnn50 | Percentage of adjacent RR intervals with differences above 50 ms between them. It is the proportion of successive RR intervals that differ by more than 50 ms, expressed as a percentage. It indicates PNS activity |
| LF norm | Low frequency normalized unit. It is the LF power normalized to total power minus VLF power, indicating the relative balance of LF power. It is used to assess relative SNS |
| HF norm | High frequency normalized unit. It is the HF power normalized to total power minus VLF power, indicating the relative balance of HF power. It is used to assess relative PNS activity |
| SDNN | Standard deviation of average normal to normal RR intervals. It is a measure of overall HRV, reflecting both sympathetic and parasympathetic influences. It indicates overall ANS activity |
HF – High frequency; HF norm – High frequency normalized unit; HR – Heart rate; LF – Low frequency; LF/HF ratio – Low frequency to high frequency ratio; LF norm – Low frequency normalized unit; RR – duration between two consecutive heartbeats; RMSSD – Root mean square of successive differences; SDNN – Standard deviation of average normal to normal RR intervals; TP – Total power; Nn50 – number of times per hour that the difference between two consecutives RR intervals exceeds 50 ms; Pnn50 – Percentage of adjacent RR intervals with differences above 50 ms between them; VLF – Very low frequency; HRV – Heart rate variability, ANS: Autonomic nervous system, PNS: Peripheral nervous system
Supplementary Table 2.
Search strategy for PubMed
| Search ID | Search terms |
|---|---|
| 1 | Physiotherapy OR physical therapy OR modalities OR exercise OR training OR massage OR manual therapy OR mobilization OR mobilisation OR manipulation OR myofascial release OR electric stimulation OR TENS OR transcutaneous electrical nerve stimulation OR short wave OR shock wave OR ESWT OR breathing exercise OR ultrasound OR laser OR Interferential OR vagus nerve OR tape |
| 2 | Spine OR cervicogenic headache OR cervical OR neck OR thoracic OR lumbar OR back OR pelvic OR sacroiliac OR spondylolisthesis OR spondylosis OR spondylitis OR backache OR dorsalgia |
| 3 | Heart rate variability OR heart rate modulation OR heart rate biomarkers OR heart rate markers OR autonomic nervous system OR autonomic function OR autonomic activity OR autonomic response OR autonomic effect OR autonomic modulation OR sympathetic OR parasympathetic |
| 4 | 1 AND 2 AND 3 |
| 5 | limit 4 to (English language and humans) |
Study selection
Initially, both reviewers (H.A.A. and H.A) screened the studies and removed duplicates using the Covidence platform (Veritas Health Innovation Ltd, Melbourne, 2018). Subsequent eligibility screening of titles, abstract, and full-text articles was carried out independently by both reviewers. The search was limited to peer-reviewed randomized clinical trials (RCTs), published in English. Included studies involved participants aged ≥18 years, who were diagnosed with any pain condition in any region of the spine (cervical, thoracic, lumbar, or sacroiliac). The interventions of interest were any physiotherapy-related techniques. The comparisons were any intervention. The outcome measure was HRV. Excluded studies were those classified as grey literature, conference abstracts, reviews, and those lacking full-text availability. Additionally, studies involving participants with spinal cord injury were excluded. Any disagreements or discrepancies among the two reviewers were resolved through discussion and consensus. In cases where consensus could not be reached, a third senior reviewer (A.M.A.) was consulted to mediate and provide a final decision.
Risk of bias assessment
The PEDro scale, a valid and reliable tool for assessing methodological quality and risk of bias of clinical trials,[17,18] was employed in this review. This 11-item scale assigns scores ranging from 0 to 10, with higher scores indicating superior methodological quality. Scores were classified into four categories: poor (1 to 3), fair (4 to 5), good (6 to 8), and excellent (9 to 10).[18] The included studies were independently assessed by H.A.A. and H.A. Any discrepancies in scoring were resolved through discussion or, if necessary, by consultation with a third senior reviewer (A.M.A.).
Evidence certainty assessment (GRADE)
Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework.[19] Outcomes derived from randomized controlled trials initially started at high certainty and were downgraded based on risk of bias, inconsistency, indirectness, imprecision, and publication bias. Risk of bias was considered according to methodological limitations of contributing studies, informed by PEDro scores, and downgrading was applied when such limitations were judged likely to influence the pooled estimate. Heterogeneity was assessed using the I² statistic, while imprecision was evaluated based on confidence interval (CI) width and total sample size. Final certainty ratings were classified as high, moderate, low, or very low.
Data extraction
The principal reviewer (H.A.A.) extracted the following data from each included study: authors and year, sample size, sex, age, HRV duration, study duration, intervention groups, outcome measures, and results. The second reviewer (H.A.) independently reviewed the extracted data to ensure accuracy. In cases where relevant outcomes were incompletely reported, the authors of the original studies were contacted to request the missing information. Data were synthesized using a qualitative/narrative approach.
Data synthesis
Quantitative data analysis was performed using Review Manager (version 5.4, Cochrane Collaboration, 2020).[20] Meta-analysis was conducted to calculate the pooled standardized mean difference (SMD) with 95% CIs for the included studies. The data included in the meta-analyses were restricted to each HRV-related parameter with a minimum of two studies. Heterogeneity across trials was assessed using the I2 statistic. A random-effects model was used because of the presence of moderate to substantial statistical heterogeneity (I2 > 50%), the small number of studies, and the conceptual differences in interventions across trials.[21] Subgroup analyses were conducted to separately explore the effects of interventions on LBP and neck pain. Statistical significance was set at P < 0.05.
RESULTS
Study selection
The PRISMA flow chart is presented in Figure 1. The initial database search yielded 3911 records. After removing duplicates and screening abstracts for relevance, 27 full-text articles were retrieved. Sixteen studies met the inclusion criteria and were included in the review and analysis.
Figure 1.
PRISMA flow chart of the study selection
Study characteristics
The included studies were published between 2008 and 2021. Nine studies evaluated the impact of physiotherapy on HRV in individuals with LBP, while seven studies focused on neck pain. The sample size of the included studies ranged from 20 to 123 participants. The follow-up period reported in the studies varied widely, ranging from 1 week to 21.5 months. Table 1 provides a detailed summary of the characteristics of the included studies.
Table 1.
Characteristics of the included studies (n=16)
| Author, year | Spinal condition | Sample size | Sex | Mean age (mean±SD) | HRV duration (recorder) | Study duration |
|---|---|---|---|---|---|---|
| Buttagat et al., 2011[30] | Back pain |
n: 36 EG: 18 CG: 18 |
80% male | EG: 22.9±3.4 CG: 22.3±2.6 |
10 min (ECG) | 7 months |
| Díaz-Sáez et al., 2021[32] | Chronic LBP |
n: 60 EG 1: 15 EG 2: 15 CG 1: 15 CG 2: 15 |
53.3% female | EG 1: 39.0±14.2 EG 2: 36.2±13.0 CG 1: 41.0±13.4 CG 2: 35.9±14.1 |
NR (MC-3MY, MC-5D and MC-6SY sensors) | 7 months |
| Espejo-Antúnez et al., 2021[7] | Chronic LBP |
n: 49 EG: 25 CG: 24 |
100% male | EG: 37.0±16.6 CG: 40.0±15.0 |
30 min (Firstbeat Bodyguard) | NR |
| Galaasen Bakken et al., 2021[8] | Chronic neck pain |
n: 123 EG: 62 CG: 61 |
55.7% female | EG: 57.0±14.0 CG: 58.0±13.7 |
5 min (First Beat ECG) | 16 months |
| Hu et al., 2021[9] | Chronic LBP |
n: 100 EG: 46 CG: 36 |
54% female | EG: 50.8±15.3 CG: 48.9±14.3 |
NR (ZSY-1 HR Variation Detector) | 6 months |
| La Touche et al., 2013[24] | Cervico-craniofacial pain |
n: 32 EG: 16 CG: 16 |
65.6% female | EG: 33.2±9.5 CG: 34.6±7.8 |
10 min (I-330-C2 + 6-channel biofeedback system) | 17 months |
| Matsubara et al., 2011[33] | Chronic neck pain |
n: 33 EG 1: 11 EG 2: 11 CG: 11 |
100% female | EG1: 35.5±6.4 EG2: 37.2±7.0 CG: 34.8±4.0 |
10 min (ECG) | NR |
| Morikawa et al., 2017[31] | Chronic neck pain |
n: 21 EG: 11 CG:10 |
100% female | EG: 23.8±0.9 CG: 23.0±1.0 |
NR (V5 chest leads ECG) | NR |
| Roy et al., 2009[25] | Acute LBP |
n: 20 EG: 10 CG: 10 |
60% female | EG: 35.7±11.7 CG: 44.7±9.8 |
5 min (Suunto watch, model T6) | 4 months |
| Shiro et al. 2012[22] | Chronic neck and shoulder pain |
n: 30 EG: 14 CG: 12 |
100% female | EG: 29.5±4.1 CG: 28.7±4.6 |
5 min (potable ECG) | NR |
| Telles et al., 2016[34] | Chronic LBP |
n: 45 EG: 21 CG: 21 |
51.1 male | EG: 34.6±6.5 CG: 36.6±6.0 |
5 min (ECG) | 8 months |
| Win et al., 2015[28] | Acute neck pain |
n: 20 EG: 10 CG: 10 |
55% male | EG: 20±2.0 CG: 21±1.0 |
5 min (First Beat) | 1 week |
| Younes et al., 2017[23] | Acute LBP |
n: 22 EG: 10 CG: 7 |
100% male | EG: 31±9.0 CG: 28±7.0 |
7 min (ECG) | 1 week |
| Yung et al., 2020[26] | Neck pain |
n: 43 EG: 22 CG: 21 |
53.5% female | EG: 29±9.1 CG: 30.4±9.6 |
NR (OMRON HEM-790IT) | 21.5 months |
| Zavarize et al., 2016[29] | LBP |
n: 21 EG: 10 CG: 11 |
81% female | EG: 47.3±NR CG: 46.8±NR |
5 min (Polar Pro-Trainer 5) | 5 weeks |
| Zhang et al., 2008[27] | Acute LBP |
n: 36 EG: 18 CG:18 |
69.4% male |
n: 34±NR EG: NR CG: NR |
NR (Biocom) | 4 weeks |
LBP – Low back pain; EG – Experimental group; CG – Comparison group; NR – Not reported; ECG – Electrocardiography; HRV – Heart rate variability
Risk of bias assessment
The mean PEDro score of all RCTs was 5.8 of 10, ranging from 3 to 9. Figure 2 presents a detailed overview of the risk of bias assessment for all included studies. While all studies, except one,[22] reported random allocation of participants, only four studies[8,23,24,25] reported participant blinding. Additionally, only one study[26] reported therapist blinding. All studies, except three trials,[27,28,29] reported both point estimates and measures of variability, as well as between-group comparisons. Eight studies showed a lower risk of bias (score ≥6),[7,8,9,23,24,26,30,31] whereas eight studies demonstrated a higher risk of bias (score <6).[22,25,27,28,29,32,33,34]
Figure 2.
Risk of bias assessment
Meta-analysis
A meta-analysis was conducted to assess the impact of HRV in 11 studies[7,8,9,24,25,26,27,28,29,30,34] after excluding 5 studies[22,23,31,32,33] due to insufficiently reported statistical data. Subgroup analyses were conducted on a minimum of two studies that included similar HRV parameters for both LBP[7,9,23,25,27,29,30,32,34] and neck pain.[8,22,24,26,28,31,33]
Nine studies assessed HRV-related changes in individuals with mechanical non-specific acute and chronic LBP.[7,9,23,25,27,29,30,32,34] However, two studies[23,32] were excluded from the meta-analysis due to a lack of reported statistical values. Seven studies assessed HRV-related changes in individuals with mechanical non-specific acute and chronic neck pain.[8,22,24,26,28,31,33] However, three studies[22,31,33] were excluded from meta-analysis due to a lack of reported statistical values.
HRV changes in LBP
The experimental groups received various physiotherapy interventions, including exercise, manual therapy, motor imagery, virtual games, dry needling, and electro-thermal modalities. Comparison groups received sham treatments, standard care, or observation only. The HRV parameters used as outcome were heart rate (HR), root mean square of successive differences (RMSSD), total power (TP), low frequency (LF), high frequency (HF), low frequency to high frequency ratio (LF/HF ratio), duration between two consecutive heartbeats (RR), very low frequency (VLF), number of times per hour that the difference between two consecutive RR intervals exceed 50 ms (Nn50), percentage of adjacent RR intervals with differences >50 ms (Pnn50), low frequency normalized unit (LF norm), high frequency normalized unit (HF norm), and standard deviation of average normal to normal RR intervals (SDNN). However, only seven HRV parameters (HR, RMSSD, LF/HF ratio, TP, VLF, LF norm, and HF norm) were analyzed in at least two studies. The measure endpoints of HRV parameters were immediate,[7,25,29,30,32] 1 week,[23] 4 weeks,[27] 12 weeks,[34] and 24 weeks.[9]
Within-group improvements were observed in the experimental group in the TP, LF, HF, LF/HF ratio, HR, RMSSD, LF norm, HF norm, and Pnn50. For the comparison group, improvements were observed in the LF/HF ratio and HR [Table 2]. For between-group analysis, the pooled effect size analysis across the seven studies revealed no statistically significant differences between both groups for any of the HRV measures (HR SMD [95% CI]): −0.06 bpm [−0.69, 0.57]; RMSSD: 0.60 ms [−0.04, 1.23]; LF/HF ratio: −0.13 [−0.50, 0.24]; TP: 0.30 ms2 [−0.50, 1.09]; VLF: −0.24 ms2 [−0.77,0.28]; LF norm: −0.12 nu [−0.63, 0.38]; and HF norm: 0.28 nu [– 0.12, 0.68]). The total pooled effect size was 0.12 [−0.10, 0.32] [Figure 3].
Table 2.
Results of the studies that investigated low back pain
| Author, year | Experimental group | Comparison group | Measurement time | Outcome measures | Within-group difference | Between-groups difference | |
|---|---|---|---|---|---|---|---|
| Buttagat et al., 2011[30] | Traditional Thai massage for 30 min | Rest on bed | Immediate | TP LF HF LF/HF |
EG TP: ↑ LF: ↑ HF: ↑ LF/HF: ↓ |
CG TP: ↑* LF: ↑* HF: ↓* LF/HF: ↑ |
TP: Significant difference favoring EG LF: No difference HF: Significant difference favoring EG LF/HF: Significant difference favoring EG |
| Díaz-Sáez et al., 2021[32] | Motor imagery | Action observation | Immediate | HR | EG HR: ↑ |
CG HR: ↑ |
HR: No difference |
| Espejo-Antúnez et al., 2021[7] | Interferential current therapy + home exercises | Sham interferential current therapy + home exercises | Immediate | HR RMSSD |
EG HR: ↓ RMSSD: ↑ |
CG HR: ↓ RMSSD: ↑* |
HR: No difference RMSSD: Significant difference favoring EG |
| Hu et al., 2021[9] | Silver needle therapy + physiotherapy (polarized light and ultrasonic) | Physiotherapy (polarized light and ultrasonic) | 6 months | LF/HF | EG LF/HF: ↑* |
CG LF/HF: ↑* |
LF/HF: No difference |
| Roy et al., 2009[25] | Thrust manipulation to lumbar spine | 5 s of pressure to lumbar spine | Immediate | RR VLF HF norm LF/HF |
Not reported | RR: No difference VLF: Significant difference favoring EG HF: Significant difference favoring EG LF/HF: No difference |
|
| Telles et al., 2016[34] | Yoga | Standard care (analgesics and NSAIDs) | 3 months | RR RMSSD Nn50 Pnn50 LF/HF LF norm HF norm |
EG RR: ↑* RMSSD: ↑* Nn50: ↑* Pnn50: ↑ LF/HF: ↓* LF norm: ↓ HF norm: ↑ |
CG RR: ↓* RMSSD: ↓* Nn50: ↓* Pnn50: ↓* LF/HF: ↑* LF norm: ↑* HF norm: ↓* |
All parameters: No difference |
| Younes et al., 2017[23] | Manipulation to lumbar spine | Sham manipulation | 1 week | RR RMSSD LF/HF |
Not reported | RR: No difference RMSSD: Significant difference favoring EG LF/HF: No difference |
|
| Zavarize et al., 2016[29] | Physiotherapy (shortwaves and therapeutic exercises) + virtual games | Physiotherapy (shortwaves and therapeutic exercises) | Immediate | RMSSD Pnn50 | EG RMSSD: ↓ Pnn50: ↓ |
CG RMSSD: ↑* Pnn50: ↑* |
Not reported |
| Zhang et al., 2008[27] | Manual adjustments + Biofreeze | Manual adjustments | 4 weeks | HR SDNN RMSSD TP VLF LF norm HF norm |
EG HR: ↑* SDNN: ↑* RMSSD: ↑* TP: ↑* VLF: ↑* LF norm: ↓* HF norm: ↑* |
CG HR: ↑* SDNN: ↓* RMSSD: ↓* TP: ↓* VLF: ↓* LF norm: ↓* HF norm: ↑* |
Not reported |
All changes were statistically significant (P<0.05) except for those parameters with an asterisk (*), which showed no significant difference. CG – Comparison group; EG – Experimental group; HF – High frequency; HF norm – High frequency normalized unit; HR – Heart rate; LF – Low frequency; LF/HF ratio – Low frequency to high frequency ratio; LF norm – Low frequency normalized unit; Nn50 – number of times per hour that the difference between two consecutives RR intervals exceeds 50 ms; Pnn50 – Percentage of adjacent RR intervals with differences above 50 ms between them; RR – duration between two consecutive heartbeats; RMSSD – Root mean square of successive differences; SDNN – Standard deviation of average normal to normal RR intervals; TP – Total power; VLF – Very low frequency; ↑ – Increase; ↓ – Decrease; NASIDs – Nonsteroidal anti-inflammatory drugs
Figure 3.
Forest plot of the meta-analysis of heart rate variability parameters for low back pain. HR – Heart rate; RMSSD – Root mean square of successive differences; LF/HF ratio – Low frequency to high frequency ratio; VLF – Very low frequency; LF norm – Low frequency normalized unit; HF norm – High frequency normalized unit
HRV changes in neck pain
The experimental group received various forms of manual therapy, except for one study that used isometric exercise. Comparison groups received sham treatment, exercise, different types of manual therapy, no intervention, or asymptomatic individuals. The HRV parameters used as outcomes were RR, RMSSD, SDNN, LF, HF, LF/HF ratio, TP, HR, LF norm, and HF norm. However, only four HRV parameters (HR, RR, SDNN, and LF/HF ratio) were analyzed in at least two studies. All HRV parameters were measured immediately,[22,24,26,28,31,33] except for one study[8] that assessed outcomes at 2-week intervals.
Within-group improvements were observed in the experimental group in the HR, HF, SDNN, LF norm, HF norm, and LF/HF ratio. For the comparison group, improvements were observed in the LF/HF ratio, LF norm, and HF norm [Table 3]. The pooled effect size analysis across the four studies revealed no statistically significant differences between both groups in any of the HRV measures (HR SMD [95% CI]): 0.57 bpm [−0.33,1.47]; RR: −0.04 ms [−0.74, 0.65]; SDNN: 0.17 ms [−0.79, 1.12]; and LF/HF ratio: −0.63 [−2.20, 0.93]). The total pooled effect size was 0.09 (−0.29, 0.46) [Figure 4].
Table 3.
Results of the studies investigated neck pain
| Author | Experimental group | Comparison group | Measurement time | Outcome measures | Within-group difference | Between-group difference | |
|---|---|---|---|---|---|---|---|
| Galaasen Bakken et al., 2021[8] | Spinal manipulative therapy + home stretching exercises | Home stretching exercises alone | Two weeks | RR RMSSD SDNN LF HF LF/HF TP |
EG RR: ↓* RMSSD: ↓* SDNN: ↓* LF: ↓* HF: ↓* LF/HF: ↑* TP: ↓* |
CG RR: ↓* RMSSD: ↓* SDNN: ↓* LF: ↓* HF: ↓* LF/HF: No change TP: ↓* |
All parameters: No difference |
| La Touche et al., 2013[24] | Anterior-posterior upper cervical mobilization | Sham mobilization | Immediate | HR | EG HR: ↑* |
CG HR: ↓* |
HR: Significant difference favoring EG |
| Matsubara et al., 2011[33] | EG1: Acupressure on local acupuncture points EG2: Acupressure on distal acupuncture points |
No stimuli | Immediate | HR LF HF LF/HF |
EG1 HR: ↓ LF: ↑* HF: ↑ LF/HF: ↓* EG2 HR: ↓* LF: ↓* HF: ↓* LF/HF: ↑* |
CG HR: ↓* LF: ↑* HF: ↑* LF/HF: ↑* |
Not reported |
| Morikawa et al., 2017[31] | Compression on myofascial trigger points | Compression on nonmyofascial trigger points | Immediate | HR LF HF LF/HF |
Not reported | HR: No difference LF: Significant difference favoring EG HF: Significant difference favoring EG LF/HF: Significant difference favoring EG |
|
| Shiro et al., 2012[22] | Trapezius isometric exercises in patients | Trapezius isometric exercises in asymptomatic participants | Immediate | LF/HF | EG LF/HF: ↑* |
CG LF/HF: ↑ |
Not reported |
| Win et al., 2015[28] | Cervical manipulation for neck pain patient | Cervical manipulation for asymptomatic participants | Immediate | HR SDNN LF norm HF norm LF/HF |
EG Upper cervical HR: ↓* SDNN: ↑ LF norm: ↓ HF norm: ↑ LF/HF: ↓ Lower cervical HR: ↑* SDNN: ↑ LF norm: ↓ HF norm: ↑ LF/HF: ↓ |
CG Upper cervical HR: No change SDNN: ↑ LF norm: ↓ HF norm: ↑ LF/HF: ↓ Lower cervical HR: ↓* SDNN: ↓* LF norm: ↑ HF norm: ↓ LF/HF: ↑ |
Not reported |
| Yung et al., 2020[26] | Anerio-posterior nonthrust manipulation | Transverse/lateral nonthrust manipulation | Immediate | HR | EG HR: ↑* |
CG HR: ↑* |
HR: No difference |
All changes were statistically significant (P<0.05) except for those parameters with an asterisk (*), which showed no significant difference. CG – Comparison group; EG – Experimental group; HF – High frequency; HF norm – High frequency normalized unit; HR – Heart rate; LF – Low frequency; LF/HF ratio – Low frequency to high frequency ratio; LF norm – Low frequency normalized unit; RR – duration between two consecutive heartbeats; RMSSD – Root mean square of successive differences; SDNN – Standard deviation of average normal to normal RR intervals; TP – Total power; ↑ – Increase; ↓ – Decrease
Figure 4.
Forest plot of the meta-analysis of heart rate variability parameters for neck pain. HR – Heart rate; RR – Duration between two consecutive heartbeats; SDNN – Standard deviation of average normal to normal RR intervals; LF/HF ratio – Low frequency to high frequency ratio
GRADE framework for evidence certainly
Certainty of evidence using the GRADE approach for HRV outcomes ranged from moderate to very low across the back and neck meta-analysis. The back-related outcomes, RMSSD demonstrated low-certainty evidence of a potential improvement following experimental interventions, while HR, TP, VLF, and normalized frequency-domain measures showed low-certainty evidence of no clear between-group differences, largely due to imprecision and, in some outcomes, substantial heterogeneity. The LF/HF ratio exhibited moderate certainty, with no clear effect observed [Table 4]. Neck-related outcomes, HR, RR interval, and SDNN were supported by low-certainty evidence, whereas the LF/HF ratio demonstrated very low-certainty evidence, primarily due to considerable inconsistency and methodological limitations across included trials [Table 5].
Table 4.
Grading of Recommendations Assessment, Development and Evaluation summary of findings for back pain-related outcomes
| Outcomes | Studies (n) | SMD (95% CI) | I2 (%) | Certainty (GRADE) | Reason for downgrading |
|---|---|---|---|---|---|
| HR | 2 RCTs (85) | −0.06 (−0.69 to 0.57) | 53 | Low | Inconsistency (−1); Imprecision (−1) |
| RMSSD (ms) | 4 RCTs (151) | 0.60 (−0.04 to 1.23) | 71 | Low | Inconsistency (−1); Imprecision (−1) |
| LF/HF ratio | 4 RCTs (201) | −0.13 (−0.50 to 0.24) | 30 | Moderate | Imprecision (−1) |
| Total Power | 2 RCTs (72) | 0.30 (−0.50 to 1.09) | 65 | Low | Inconsistency (−1); Imprecision (−1) |
| VLF (ms2) | 2 RCTs (56) | −0.24 (−0.77 to 0.28) | 0 | Low | Imprecision (−2) |
| LF (Normalized) (ms2) | 3 RCTs (101) | −0.12 (−0.63 to 0.38) | 0 | Low | Imprecision (−1); Risk of bias (−1) |
| HF (Normalized) (ms2) | 3 RCTs (101) | 0.28 (−0.12 to 0.68) | 0 | Low | Imprecision (−1); Risk of bias (−1) |
GRADE – Grading of Recommendations Assessment, Development and Evaluation; CI – Confidence interval; HF – High-frequency power; I2 – Heterogeneity statistic; LF – Low-frequency power; RCT – Randomized controlled trial; RMSSD – Root mean square of successive differences; SMD – Standardized mean difference; VLF – Very low-frequency power; HR –Heart rate
Table 5.
Grading of Recommendations Assessment, Development and Evaluation summary of findings for neck pain-related outcomes
| Outcomes | Studies (n) | SMD (95% CI) | I2 (%) | Certainty (GRADE) | Reason for downgrading |
|---|---|---|---|---|---|
| HR | 3 RCTs (95) | 0.57 (−0.33 to 1.47) | 77 | Low | Inconsistency (−1); Imprecision (−1) |
| RR interval (ms) | 2 RCTs (155) | −0.04 (−0.74 to 0.65) | 69 | Low | Inconsistency (−1); Imprecision (−1) |
| SDNN | 2 RCTs (143) | 0.17 (−0.79 to 1.12) | 75 | Low | Inconsistency (−1); Imprecision (−1) |
| LF/HF ratio (ms2) | 2 RCTs (143) | −0.63 (−2.20 to 0.93) | 88 | Very low | Inconsistency (−2); Imprecision (−1) |
CI – Confidence interval; HF – High-frequency power; I2 – Heterogeneity statistic; LF – Low-frequency power; SMD – Standardized mean difference; RCT – Randomized controlled trial; SDNN – Standard deviation of normal-to-normal intervals; RR – RR interval, GRADE – Grading of Recommendations Assessment, Development and Evaluation
DISCUSSION
This systematic review aimed to assess the impact of physiotherapy interventions on ANS function, specifically HRV, in patients with neck pain and LBP. Meta-analysis of the included studies revealed no statistically significant differences in HRV parameters between the experimental and comparison groups. The HRV parameters were HR, RMMSD, LF/HF ratio, TP, VLF, RR, SDNN, LF norm, and HF norm.
Previous studies investigated the efficacy of physiotherapy interventions on ANS modulation. For instance, a systematic review of 29 studies investigated the influence of joint manipulative techniques, applied to either the spine or peripheral joints, on markers of ANS activities, namely, skin conductance, skin temperature, skin blood flow, HR, blood pressure, HRV, pupil diameter, plasma concentrations of norepinephrine, and oxy-hemoglobin.[35] Of the 29, 23 studies used healthy participants, while 6 studies included symptomatic patients (two studies included patients with neck pain, two with lateral epicondylalgia, one with LBP, and one with craniofacial). The finding revealed a probable immediate and short-term increase in skin sympathetic activity following oscillatory joint mobilization. Spinal mobilization with movement and spinal manipulation techniques did not demonstrate any changes in any markers of ANS activity.[35] Other systematic reviews on the effects of exercise interventions on HRV and cardiovascular health parameters were conducted on healthy adults. For example, endurance, coordination, and/or resistance training resulted in improvement in HRV parameters in healthy young, middle-aged,[36] and older adults aged ≥60 years.[37]
Our systematic review indicates that physiotherapy interventions do not exert a uniform influence on autonomic function, reflecting significant clinical and methodological heterogeneity. The inclusion of diverse interventions, ranging from cortical-level motor imagery to peripheral stimuli like dry needling, suggests that disparate physiological pathways, such as top–down modulation versus somato-autonomic reflexes, were engaged across studies. Furthermore, the pooling of acute and chronic pain conditions likely diluted the findings, given that baseline autonomic states and baroreflex sensitivity differ fundamentally between these populations. These factors, alongside inconsistent HRV acquisition protocols (e.g., recording duration and positioning), contribute to the variance in the pooled SMD and preclude a singular, definitive interpretation of the results.
The observed inconsistency may stem from the indirect nature of the physiotherapy interventions analyzed. Unlike vagus nerve stimulation (VNS) or targeted breathing exercises, which directly engage autonomic pathways,[38,39] the techniques in this review rely on secondary responses to musculoskeletal stimuli. For instance, VNS delivers electrical impulses that directly activate the vagal afferents to modulate heart rate,[38] while slow-breathing techniques specifically enhance baroreflex sensitivity to elevate vagal tone.[39] Because the included RCTs did not utilize these “vagal-specific” protocols, our results likely reflect the more subtle or variable autonomic modulation inherent in conventional physiotherapy. This distinction is critical: it suggests that while physiotherapy may influence the ANS, its effect size is highly contingent on specific study parameters, unlike the more robust effects seen in direct autonomic interventions.
Strengths and limitations
The current review has several strengths. To our knowledge, it is the first review summarizing the effects of physiotherapy on ANS function in spinal pain. The meta-analysis provides a quantitative view of the results, an increase in statistical power, and a resolution of uncertainty when studies disagree. However, this review has a few limitations. First, the literature search was limited to English studies, and thus may have missed articles in other languages. Another limitation was that our search was restricted to HRV parameters. Other indices such as baroreflex sensitivity, blood pressure, and skin conductance factors can be considered as indicators of the function of the ANS.
CONCLUSION
This systematic review and meta-analysis found no consistent differences in HRV parameters between physiotherapy interventions and comparative approaches. This finding may be because of variable intervention intensities, inconsistent patient adherence, and heterogeneous HRV measurement protocols. Furthermore, limited parasympathetic responsiveness in chronic populations may lower the measurable effects of treatment. These findings underscore the complexity of autonomic modulation within physiotherapy. To establish more definitive evidence, future research should utilize longitudinal designs with larger cohorts and standardized protocols. Additionally, studies should identify responsive patient subgroups and explore targeted interventions such as vagus nerve stimulation or specialized breathing exercises.
Peer review
This article was peer-reviewed by two independent and anonymous reviewers.
Data availability statement
All data generated or analyzed for the meta-analysis are included in this published article.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
REFERENCES
- 1.Dmitry K, Dermot M. The role of autonomic nervous system in pain chronicity. In: María Elena HA, Gonzalo Emiliano AA, editors. Topics in Autonomic Nervous System. Ch. 3. Rijeka: IntechOpen; 2023. [Google Scholar]
- 2.Hohenschurz-Schmidt DJ, Calcagnini G, Dipasquale O, Jackson JB, Medina S, O’Daly O, et al. Linking pain sensation to the autonomic nervous system: The role of the anterior cingulate and periaqueductal gray resting-state networks. Front Neurosci. 2020;14:147. doi: 10.3389/fnins.2020.00147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Minghelli B. Musculoskeletal spine pain in adolescents: Epidemiology of non-specific neck and low back pain and risk factors. J Orthop Sci. 2020;25:776–80. doi: 10.1016/j.jos.2019.10.008. [DOI] [PubMed] [Google Scholar]
- 4.Hallman DM, Lyskov E. Autonomic Regulation in Musculoskeletal Pain. In: Ghosh S, editor. Pain in Perspective. Rijeka: IntechOpen; 2012. Chapter 3. [Google Scholar]
- 5.Trulsson Schouenborg A, Rivano Fischer M, Bondesson E, Jöud A. Physiotherapist-led rehabilitation for patients with chronic musculoskeletal pain: Interventions and promising long-term outcomes. BMC Musculoskelet Disord. 2021;22:910. doi: 10.1186/s12891-021-04780-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Chiang JK, Lin YC, Hung TY, Kao HH, Kao YH. The impact on autonomic nervous system activity during and following exercise in adults: A meta-regression study and trial sequential analysis. Medicina (Kaunas) 2024;60:1223. doi: 10.3390/medicina60081223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Espejo-Antúnez L, Fernández-Morales C, Cardero-Durán ML, Toledo-Marhuenda JV, Díaz-Mancha JA, Albornoz-Cabello M. Detection of changes on parameters related to heart rate variability after applying current interferential therapy in subjects with non-specific low back pain. Diagnostics (Basel) 2021;11:2175. doi: 10.3390/diagnostics11122175. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Galaasen Bakken A, Eklund A, Hallman DM, Axén I. The effect of spinal manipulative therapy and home stretching exercises on heart rate variability in patients with persistent or recurrent neck pain: A randomized controlled trial. Chiropr Man Therap. 2021;29:48. doi: 10.1186/s12998-021-00406-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Hu X, Dong S, Zhang B, Wang X, Yin Y, Liu C, et al. Efficacy of silver needle therapy for the treatment of chronic nonspecific low back pain: A prospective, single-center, randomized, parallel-controlled clinical trial. Trials. 2021;22:75. doi: 10.1186/s13063-021-05040-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Keter DL, Bialosky JE, Brochetti K, Courtney CA, Funabashi M, Karas S, et al. The mechanisms of manual therapy: A living review of systematic, narrative, and scoping reviews. PLoS One. 2025;20:e0319586. doi: 10.1371/journal.pone.0319586. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Gourine AV, Ackland GL. Cardiac vagus and exercise. Physiology (Bethesda) 2019;34:71–80. doi: 10.1152/physiol.00041.2018. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Espejo-Antúnez L, Fernández-Morales C, Hernández-Sánchez S, Cardero-Durán ML, Toledo-Marhuenda JV, Albornoz-Cabello M. The impact on the stress-associated autonomic response of physiotherapy students receiving interferential current in an electrotherapy training session. Int J Environ Res Public Health. 2022;19:13348. doi: 10.3390/ijerph192013348. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Daibes M, Almarie B, Andrade MF, Vidigal GP, Aranis N, Gianlorenco A, et al. Do pain and autonomic regulation share a common central compensatory pathway? A meta-analysis of HRV metrics in pain trials. NeuroSci. 2025;6:62. doi: 10.3390/neurosci6030062. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.GBD 2021 Low Back Pain Collaborators. Global, regional, and national burden of low back pain, 1990-2020, its attributable risk factors, and projections to 2050: A systematic analysis of the Global Burden of Disease Study 2021. Lancet Rheumatol. 2023;5:e316–29. doi: 10.1016/S2665-9913(23)00098-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi: 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health. 2017;5:258. doi: 10.3389/fpubh.2017.00258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.de Morton NA. The PEDro scale is a valid measure of the methodological quality of clinical trials: A demographic study. Aust J Physiother. 2009;55:129–33. doi: 10.1016/s0004-9514(09)70043-1. [DOI] [PubMed] [Google Scholar]
- 18.Cashin AG, McAuley JH. Clinimetrics: Physiotherapy evidence database (PEDro) scale. J Physiother. 2020;66:59. doi: 10.1016/j.jphys.2019.08.005. [DOI] [PubMed] [Google Scholar]
- 19.Guyatt GH, Oxman AD, Vist GE, Kunz R, Falck-Ytter Y, Alonso-Coello P, et al. GRADE: An emerging consensus on rating quality of evidence and strength of recommendations. BMJ. 2008;336:924–6. doi: 10.1136/bmj.39489.470347.AD. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Nordic Cochrane Centre TCC. Review Manager (RevMan) Copenhagen, Denmark. 2014 [Google Scholar]
- 21.Stogiannis D, Siannis F, Androulakis E. Heterogeneity in meta-analysis: A comprehensive overview. Int J Biostat. 2024;20:169–99. doi: 10.1515/ijb-2022-0070. [DOI] [PubMed] [Google Scholar]
- 22.Shiro Y, Arai YC, Matsubara T, Isogai S, Ushida T. Effect of muscle load tasks with maximal isometric contractions on oxygenation of the trapezius muscle and sympathetic nervous activity in females with chronic neck and shoulder pain. BMC Musculoskelet Disord. 2012;13:146. doi: 10.1186/1471-2474-13-146. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Younes M, Nowakowski K, Didier-Laurent B, Gombert M, Cottin F. Effect of spinal manipulative treatment on cardiovascular autonomic control in patients with acute low back pain. Chiropr Man Therap. 2017;25:33. doi: 10.1186/s12998-017-0167-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.La Touche R, París-Alemany A, Mannheimer JS, Angulo-Díaz-Parreño S, Bishop MD, Lopéz-Valverde-Centeno A, et al. Does mobilization of the upper cervical spine affect pain sensitivity and autonomic nervous system function in patients with cervico-craniofacial pain? A randomized-controlled trial. Clin J Pain. 2013;29:205–15. doi: 10.1097/AJP.0b013e318250f3cd. [DOI] [PubMed] [Google Scholar]
- 25.Roy RA, Boucher JP, Comtois AS. Heart rate variability modulation after manipulation in pain-free patients versus patients in pain. J Manipulative Physiol Ther. 2009;32:277–86. doi: 10.1016/j.jmpt.2009.03.003. [DOI] [PubMed] [Google Scholar]
- 26.Yung E, Oh C, Wong M, Grimes JK, Barton EM, Ali MI, et al. Non-thrust cervical manipulations reduce short-term pain and decrease systolic blood pressure during intervention in mechanical neck pain: A randomized clinical trial. J Man Manip Ther. 2020;28:82–93. doi: 10.1080/10669817.2019.1646985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Zhang J, Enix D, Snyder B, Giggey K, Tepe R. Effects of Biofreeze and chiropractic adjustments on acute low back pain: A pilot study. J Chiropr Med. 2008;7:59–65. doi: 10.1016/j.jcme.2008.02.004. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Win NN, Jorgensen AM, Chen YS, Haneline MT. Effects of upper and lower cervical spinal manipulative therapy on blood pressure and heart rate variability in volunteers and patients with neck pain: A randomized controlled, cross-over, preliminary study. J Chiropr Med. 2015;14:1–9. doi: 10.1016/j.jcm.2014.12.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Zavarize SF, Paschoal MA, Wechsler SM. Effects of physiotherapy associated to virtual games in pain perception and heart rate variability in cases of low back pain. Manual Ther Posturol Rehabil J. 2016;2016:1–7. [Google Scholar]
- 30.Buttagat V, Eungpinichpong W, Chatchawan U, Kharmwan S. The immediate effects of traditional Thai massage on heart rate variability and stress-related parameters in patients with back pain associated with myofascial trigger points. J Bodyw Mov Ther. 2011;15:15–23. doi: 10.1016/j.jbmt.2009.06.005. [DOI] [PubMed] [Google Scholar]
- 31.Morikawa Y, Takamoto K, Nishimaru H, Taguchi T, Urakawa S, Sakai S, et al. Compression at myofascial trigger point on chronic neck pain provides pain relief through the prefrontal cortex and autonomic nervous system: A pilot study. Front Neurosci. 2017;11:186. doi: 10.3389/fnins.2017.00186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Díaz-Sáez MC, La Touche R, Cuenca-Martínez F. Comparative analysis of the autonomic nervous system response during movement representation in healthy individuals and patients with chronic low back pain: A prospective cohort study. Somatosens Mot Res. 2021;38:68–76. doi: 10.1080/08990220.2020.1845137. [DOI] [PubMed] [Google Scholar]
- 33.Matsubara T, Arai YC, Shiro Y, Shimo K, Nishihara M, Sato J, et al. Comparative effects of acupressure at local and distal acupuncture points on pain conditions and autonomic function in females with chronic neck pain. Evid Based Complement Alternat Med. 2011;2011:543291. doi: 10.1155/2011/543291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.Telles S, Sharma SK, Gupta RK, Bhardwaj AK, Balkrishna A. Heart rate variability in chronic low back pain patients randomized to yoga or standard care. BMC Complement Altern Med. 2016;16:279. doi: 10.1186/s12906-016-1271-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Picchiottino M, Leboeuf-Yde C, Gagey O, Hallman DM. The acute effects of joint manipulative techniques on markers of autonomic nervous system activity: A systematic review and meta-analysis of randomized sham-controlled trials. Chiropr Man Therap. 2019;27:17. doi: 10.1186/s12998-019-0235-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Grässler B, Thielmann B, Böckelmann I, Hökelmann A. Effects of different training interventions on heart rate variability and cardiovascular health and risk factors in young and middle-aged adults: A systematic review. Front Physiol. 2021;12:657274. doi: 10.3389/fphys.2021.657274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Grässler B, Thielmann B, Böckelmann I, Hökelmann A. Effects of different exercise interventions on heart rate variability and cardiovascular health factors in older adults: A systematic review. Eur Rev Aging Phys Act. 2021;18:24. doi: 10.1186/s11556-021-00278-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Austelle CW, Cox SS, Wills KE, Badran BW. Vagus nerve stimulation (VNS): Recent advances and future directions. Clin Auton Res. 2024;34:529–47. doi: 10.1007/s10286-024-01065-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Zaccaro A, Piarulli A, Laurino M, Garbella E, Menicucci D, Neri B, et al. How breath-control can change your life: A systematic review on psycho-physiological correlates of slow breathing. Front Hum Neurosci. 2018;12:353. doi: 10.3389/fnhum.2018.00353. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
All data generated or analyzed for the meta-analysis are included in this published article.