Research Review By Dr. Jeff Muir©


Download MP3

Date Posted:

October 2019

Study Title:

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


Picchiottino M, Leboeuf-Yde C, Gagey O & Hallman DM

Author's Affiliations:

CIAMS, Université Paris-Sud, Université Paris-Saclay, Orsay Cedex, France; CIAMS, Université d’Orléans, Orléans, France; Institut Franco-européen de Chiropraxie (IFEC), Ivry-sur-Seine, France; Institute for Regional Health Research, University of Southern Denmark, Odense, Denmark; Centre for Musculoskeletal Research, Department of Occupational and Public Health Sciences, University of Gävle, Sweden.

Publication Information:

Chiropractic & Manual Therapies 2019; 27: 17.

Background Information:

Despite their continued and broad use to treat musculoskeletal conditions, the mechanisms of action of joint manipulative therapies (JMT) remain unknown. Research into biomechanical (1-3) and neurophysiological (2) mechanisms have yielded incomplete answers, as has initial research into the effect of JMT on the autonomic nervous system (ANS) (4-6). Effects on the ANS such as somato-autonomic reflex modulation (7) have been proposed as potential mechanisms. Indeed, the chiropractic profession initially professed to “normalize” autonomic activity as an explanation for the treatment effect of high-velocity spinal manipulation. The true mechanism of effect, however, remains elusive.

Several literature reviews (4-6) have attempted to systematically review and meta-analyze results from studies investigating the mechanism of JMT, although they are limited by methodological concerns, including design and study quality, study quality assessment, limitations in treatment scope and the lack of a standard control intervention.

As such, the goal of this study was review and critique the existing literature and compare the acute changes in ANS markers between patients receiving JMT on spinal or peripheral joints with those undergoing a sham treatment.

Pertinent Results:

Study Characteristics:
29 studies met the inclusion criteria, after initial screening of 2267 studies. Interventions included mobilizations (n = 16 studies), ‘atypical’ mobilization (n = 1), sustained natural apophyseal glides (SNAGs) (n = 5) and high-velocity, low-amplitude thrust manipulation (HVLA) (n = 7). Treatment was generally localized to the spine, with 2 studies additionally including peripheral joint treatment.

Risk of Bias Assessment:
Risk of bias was unclear in all but 4 eligible studies, based largely on uncertainty regarding blinding of participants, the data extraction process and blinding of statisticians. With respect to specifics, 2 studies (both on mobilization) were determined to have low risk of bias while 3 (2 of which were on HVLA spinal manipulation) were deemed to have a high risk of bias.

Overall Technical Quality:
Technical quality was judged to be acceptable in 25/29 studies. The remaining studies (2 on mobilization, 2 on manipulation) were deemed to be technically deficient, based on a low technical score.

Sham Procedures:
25/29 studies defined a sham intervention as an “inactive” manual contact (i.e. no movement). 2/29 studies used a sham treatment mechanically similar to the intervention; 1/29 used a sham similar to the true intervention with less pressure and 1/29 did not describe the sham intervention.

Effect of Interventions

1. Mobilization vs. sham
  • Outcome – Skin Conductance: Moderate evidence (10 studies) suggests that treatment causes a bilateral increase in skin sympathetic nerve activity. Data pooled from 3 studies indicate significant increases over sham (mean difference 13.75, 95% CI 1.36 to 26.14, I2 = 51%, random effect, p = 0.03; 3 studies, 96 subjects) between baseline and intervention period and between baseline and the post-intervention period (mean difference 9.34, 95% CI 2.85 to 15.83, I2 = 0%, p = 0.005; 3 studies, 96 subjects).
  • Outcome: Skin Temperature: Very low quality evidence (8 studies) indicates no effect on skin sympathetic nerve activity or skin temperature. No pooling of data was possible.
  • Outcome – Skin Blood Flow: Very low quality evidence (2 studies) suggest no effect on blood flow (1 study in fact found dual effects in opposite directions [increase and decrease]).
  • Outcome – Heart Rate: Very low quality evidence (5 studies) found no effect on heart rate (beats per minute) during the intervention (mean difference −0.83 bpm, 95% CI -5.47 to 3.81, I2 = 0%, p = 0.73; 83 subjects, 2 studies) and the immediate post-intervention period (mean difference − 1.23 bpm, 95% CI -4.47 to 2.02, I2 = 0%, p = 0.46, 121 subjects). 2 other studies found a significant increase in heart rate between baseline and intervention period, while 1 study reported a significant increase in the post-intervention period.
  • Outcome – Blood Pressure: Very low quality evidence (5 studies) indicates no effect on systolic blood pressure during the intervention period (mean difference − 2.02 mmHg, 95% CI -6.96 to 2.92, I2 = 31%, p = 0.42, 83 subjects) and the post-intervention period (mean difference − 1.02 mmHg, 95% CI -5.77 to 3.72, I2 = 0%, p = 0.67, 83 subjects). No effect was noted on diastolic blood pressure during either period (mean difference − 0.07 mmHg, 95% CI -3.09 to 2.94, I2 = 0%, p = 0.96, 83 subjects; mean difference 0.32 mmHg, 95% CI -2.49 to 3.14, I2 = 0%, p = 0.82, 83 subjects). One study noted no effect on arterial blood pressure; 2 studies noted significantly increased systolic blood pressure compared to sham (no pooled analysis).
  • Outcome – Heart Rate Variability: Low quality evidence (1 study) indicates no effect on heart rate variability.
  • Outcome – Respiratory Rate: Very low quality evidence (3 studies) indicates a significant increase in respiratory rate compared to sham. No pooled analysis was possible.
2. Atypical mobilization technique vs. sham
  • Outcome – Alpha amylase activity: Very low quality evidence (1 study) indicates a significant decrease in sympathetic activity in the salivary glands within 10 minutes of treatment.
3. Spinal SNAGs/mobilization with movement vs. sham
  • Outcome – Skin Conductance: Low quality evidence (4 studies) indicates no effect on skin conductance in the intervention period or post-intervention period. Pooled analysis (2 studies) found no effect in the intervention (mean difference 4.62, CI 95% -2.31 to 11.55, I2 = 0%, p = 0.19, 2 studies, 60 subjects) or post-intervention (mean difference 3.99, CI 95% -3.47 to 11.44, I2 = 0%, p = 0.29, 2 studies, 60 subjects) periods.
  • Outcome – Skin Temperature: Very low quality evidence (2 studies) indicates no effect on skin temperature. No pooled analysis was possible.
3.1. Peripheral SNAGs/mobilization with movement vs. sham
  • Outcome – Skin Conductance: Very low quality evidence (1 study) suggests a significant increase in skin conductance compared with sham.
  • Outcomes – Skin Temperature, Blood Flow: Very low quality evidence (1 study) indicates a significant increase or decrease in skin temperature and blood flow compared to sham.
  • Outcomes – Heart Rate/Blood Pressure: Very low quality evidence (1 study) suggest an increase in heart rate and blood pressure when compared with sham.
4. HVLA vs. sham
  • Outcome – Heart Rate Variability: Low quality evidence (4 studies) indicated no effect on heart rate variability.
  • Outcome – Heart Rate: Very low quality evidence (3 studies) found no effect on heart rate immediately after treatment (mean difference − 1.67 bpm, 95% CI -5.33 to 1.98, I2 = 1%, p = 0.37, 3 studies).
  • Outcome – Blood Pressure: Very low quality evidence (1 study) found no effect on blood pressure immediately, 10 min and 24 hr after treatment.
  • Outcome: Pupil Diameter: Low quality evidence (1 study) found no acute effect on pupillary control within 5 min of treatment.
  • Outcome – Plasma concentrations of epinephrine and norepinephrine: Low quality evidence (1 study) found no effect on sympathoadrenal activity.
  • Outcome – Oxy-hemoglobin concentration: Very low quality evidence (1 study) found no effect on muscle sympathetic nerve activity immediately, 5 min or 30 mins after treatment.

Clinical Application & Conclusions:

The authors conclude that one type of joint manipulative therapy – mobilizations with oscillatory movements – probably produce effects on skin sympathetic nerve activity. This finding, however, has limited clinical relevance. The remaining interventions (SNAGs, HVLA) have no acute effect on the studied markers of ANS activity. They suggest that future research consider findings over longer follow-up periods and in patients with chronic pain. It is worth remembering that this study included ONLY studies that employed a sham control comparison. This is the best way to study these effects, but as a result some papers wouldn’t have made ‘the cut’.

EDITOR’S COMMENT: This is an area where unfortunately, the claims of some practitioners are outpacing our science. This relationship is interesting and the fact is, some clinical outcomes cannot be explained at this point via the existing research. There is much more work to do and I think this will be a burgeoning area in coming years as research techniques and technology advance. The main thing to address, in my opinion, is the length of treatment intervention in these studies – many of the papers in this area employ only one, or just a few, treatments. This isn’t necessarily reflective of our normal interactions with patients. Changes in the ANS likely take time to manifest and then logically would take time to reverse. We simply need more research in this area to come up with some better answers!

Study Methods:

Several databases were searched: PubMed, the Cochrane library, PsycINFO, PEDro, EMBASE, and Medline from inception until December 2017. The search was updated until July 2018 with PubMed, the Cochrane library, EMBASE, and Medline.

Eligibility Criteria:
  • Randomized studies assessing effect of JMT on ANS markers
  • JMT applied manually
  • Outcomes measured at baseline and repeated during/after intervention
  • ANS markers included: skin conductance, heart rate variability, heart rate, blood pressure, biochemical markers, pupil diameter, skin blood flow, skin temperature, respiratory rate
Data Extraction:
2 authors independently screened relevant articles. Articles were categorized based on the treatment intervention: HVLA, mobilizations, peripheral treatment.

Methodological Quality:
Articles were assessed based on the following criteria:
  1. Risk of bias, using the criteria of the Cochrane Handbook for Systematic Reviews of Interventions (8);
  2. Technical quality, using an author-developed measurement tool based on treatment intervention, treatment provider, outcomes, data acquisition plan, data cleaning and sample size calculations; and
  3. Quality of evidence summary, based on the GRADE approach (8).
Data Synthesis and Analysis:
Between group/intervention differences were determined for each outcome. When possible, data was pooled for meta-analysis, using standard meta-analytic tests for heterogeneity (Q-value and I2 statistic).

Study Strengths / Weaknesses:

  • Very strong, comprehensive search criteria.
  • Inclusion of only randomized, sham-controlled studies (which are considered the best method to study these effects).
  • Technical study quality assessment was included
  • Quality assessment was conducted using the GRADE approach.
  • Low study methodological quality of the body of research that exists to date.
  • Heterogeneity regarding study populations, interventions and treatment regimens, which did not allow for broad application of meta-analytic techniques.
  • Unclear risk of bias in the majority of studies.

Additional References:

  1. Branney J, Breen AC. Does inter-vertebral range of motion increase after spinal manipulation? A prospective cohort study. Chiropr Man Therap 2014; 22(1): 24.
  2. Nougarou F, Pagé I, Loranger M, Dugas C, Descarreaux M. Neuromechanical response to spinal manipulation therapy: effects of a constant rate of force application. BMC Complement Altern Med 2016; 16(1): 161.
  3. Funabashi M, Nougarou F, Descarreaux M, Prasad N, Kawchuk GN. Does the application site of spinal manipulative therapy alter spinal tissues loading? Spine J 2018; 18(6): 1041–52.
  4. Chu J, Allen DD, Pawlowsky S, Smoot B. Peripheral response to cervical or thoracic spinal manual therapy: an evidence-based review with meta analysis. J Man Manip Ther 2014; 22(4): 220–9.
  5. Kingston L, Claydon L, Tumilty S. The effects of spinal mobilizations on the sympathetic nervous system: a systematic review. Man Ther 2014; 19(4): 281–7.
  6. Amoroso Borges BL, Bortolazzo GL, Neto HP. Effects of spinal manipulation and myofascial techniques on heart rate variability: a systematic review. J Bodywork Mov Ther 2018; 22(1): 203–8.
  7. Sato A. Neural mechanisms of autonomic responses elicited by somatic sensory stimulation. Neurosci Behav Physiol 1997; 27(5): 610–21.
  8. Higgins JPT GSe. Cochrane handbook for systematic reviews of interventions version 5.1.0 [updated march 2011]. The Cochrane Collaboration. 2011. Available from