Research Review By Dr. Brynne Stainsby©


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Date Posted:

November 2019

Study Title:

Neurophysiological effects of high velocity and low amplitude spinal manipulation in symptomatic and asymptomatic humans
A systematic literature review


Wirth B, Gassner A, de Bruin ED et al.

Author's Affiliations:

Integrative Spinal Research Group, Department of Chiropractic Medicine, University Hospital Balgrist, Zurich, Switzerland; Health Sciences and Technology, Institute of Human Movement Sciences and Sport, ETH Zurich, Zurich, Switzerland; Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden; Intervention and Implementation Research for Worker Health, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Physiotherapy and Occupational Therapy Research Center, Directorate of Research and Education, University Hospital Zurich, Zurich, Switzerland.

Publication Information:

Spine 2019; 44(15): E914-E926.

Background Information:

Spinal manipulative therapy is the application of a high velocity, low amplitude thrust (HVLA-SMT), frequently used for the management of acute or chronic mechanical low back and neck pain or disc herniation with radiculopathy (1-3). Although its effectiveness in decreasing pain and disability has been found similar to analgesics, physical therapies and exercises, the mechanism(s) of action are not yet well understood (4-8).

Studies have suggested the mechanical input of HVLA-SMT primarily affects afferent neurons in the paraspinal tissues (9, 10) and triggers neurophysiological responses in the peripheral and central nervous systems, leading to pain inhibition (11, 12). Other studies have suggested HVLA-SMT may increase pain-pressure thresholds (13) and result in changes in Substance-P, neurotensin, oxytocin, interleukin and cortisol levels (14).

The aim of this systematic review was to summarize the current state of the literature regarding the neurophysiological effects of HVLA-SMT in asymptomatic and symptomatic humans.

Pertinent Results:

  • A total of 2532 titles and abstracts were screened for eligibility and 65 potentially relevant articles were identified for full-text screening.
  • Ultimately, 18 studies were found to be of at least moderate quality.
  • The average quality of selected studies was 17.6/24, with a range of 15-22.
Autonomic Nervous System:

Twelve studies examined the effects of HVLA-SMT on the autonomic nervous system (ANS). Blood pressure (15-19), electrocardiographic (ECG) parameters (17, 18), oxygen saturation (14, 17, 18), heart rate (17-20), heart rate variability (14, 19, 21, 22), pupil diameter (23) and skin conductance (24, 25) were used as outcome measures. Pertinent results from this work was summarized as follows:
  • For blood pressure, one study reported a significant reduction in systolic blood pressure after HVLA-SMT to the lower or upper cervical spine in normotensive adults with acute neck pain (19). No other study found an effect on blood pressure (15-18).
  • Two studies found no effect of upper thoracic HVLA-SMT on heart rate or ECG parameters (17, 18), nor did cervical HVLA-SMT affect heart rate in patients with acute neck pain (19). In patients with rotator cuff pathology, no difference was found on heart rate or respiratory rate between HVLA-SMT and sham (20).
  • Two studies examined the effects of HVLA-SMT on heart rate variability and reported an increase in low frequency (LF) and decrease in high frequency (HF) components after upper thoracic (21) or lower cervical (19) manipulation. Two other studies, however, found no significant effect of thoracic (26) or lumbar (22) HVLA-SMT on the LF/HF ratio.
  • In two studies, skin conductance in the lower limb increased after lumbar HVLA-SMT in healthy participants (30) and in patients with LBP of less than 12 weeks’ duration (25).
  • When measuring oxygen saturation in normotensive (17) and hypertensive (18) participants, no effect of upper thoracic HVLA-SMT was observed. Additionally, there was no significant difference in the level of oxygenated haemoglobin after HVLA-SMT or sham manipulation in healthy young men (14).
  • Pupil diameter did not change in patients with chronic neck pain after HVLA-SMT to the thoracic spine (23).
Spinal Reflexes:
  • Two studies examined the effects of HVLA-SMT on the H-reflex (27, 28). One study reported a substantial decrease in the H-reflex amplitude (27), while the other observed a decrease of non-normalized H-reflex amplitude in approximately one-third of the population (28).
  • One study reported a significantly increased conduction velocity of the T-reflex (tendon reflex) after HVLA-SMT but no change after sham manipulation (29).
  • Two studies examined the effects of lumbar HVLA-SMT on ‘dysfunctional segments’ (as assessed during physical exam), and results suggest minimal to no effect (30, 31). Neither study included a healthy control group, so it is unknown if there would be different responses in symptomatic participants compared to asymptomatic.
Changes Related to Alterations in Pain Intensity:

Six studies examined the effects of HVLA-SMT in neck or low back pain patients; however, only two reported on changes in pain intensity following HVLA-SMT (19, 23):
  • One study reported a significant reduction in acute neck pain intensity after HVLA-SMT, however, did not correlate this improvement with to the neurophysiological parameters studied (19).
  • Another study reported a significant reduction in pain intensity after HVLA-SMT, but did not find a difference between the intervention and sham manipulation, nor did the authors comment on a correlation between pain intensity and pupil diameter (23).

Clinical Application & Conclusions:

This review suggests the ANS is likely to be affected by HVLA-SMT, as demonstrated by changes in heart rate variability and skin conductance. It is noteworthy that it appears healthy and symptomatic subjects may respond differently; perhaps based on the baseline values of neurophysiological outcome measures or the responses of the nervous system to treatment. More work to date has included healthy subjects, so we need more research in this area on clinical populations.

Currently, the relationship between pain perception and neurophysiologic effects is not well understood in the context of HVLA-SMT. Understanding the neurophysiologic mechanisms of HVLA-SMT may help clinicians individualize treatment approaches, however, further research is required to clarify these concepts and related clinical decisions.

Study Methods:

  • A systematic search strategy was developed by three authors using the PICO (patient/problem, intervention, comparison/control, outcome) framework.
  • The systematic literature search of seven databases was performed by an experienced, professional medical librarian from inception to July 19, 2018.
  • The review was restricted to English and German-language studies that focused on the effects of HVLA-SMT to the spine in humans over 18. Studies that compared the effects of HVLA-SMT in combination with mobilization or other techniques were excluded. Studies using subjective measures, biochemical or biomechanical outcome measures were also not included.
  • Two authors screened the abstracts on basis of title, content and keywords for eligibility.
  • Two authors independently assessed study quality using a purpose-adjusted checklist of 24 items, 10 of which were related to the quality of reporting, two to external validity, seven to internal validity (bias), four to internal validity (confounding/selection bias), and one item to power (26). Uncontrolled trials and studies of poor methodological quality were excluded after quality assessment (32), and only studies scoring 60% or greater were included in this review.
  • One reviewer extracted data from included studies and built evidence tables. A second reviewer confirmed the data. Levels of evidence were determined according to the Oxford Center for Evidence-Based Medicine (33).
  • An effect was defined as “at least two studies showing a significantly greater effect (in the same direction) of HVLA-SMT compared with the control intervention on a particular neural subsystem”.

Study Strengths / Weaknesses:

  • The research question was clear and they employed a thorough and systematic search.
  • Independent screening of titles and abstracts, and full texts was conducted.
  • Only those trials assessed as being of at least moderate quality were included.
  • Assessment of risk of bias was performed with a validated set of criteria, although it is unclear if this scale was relevant for nonpharmacological studies.
  • Two authors independently extracted the data from the included articles.
  • The level of evidence for each study was reported.
  • The primary limitation of this study relates more to the quality of the body of evidence than the methodology of the review itself.
  • Although the authors used a validated tool to assess risk of bias, it may have been more appropriate to use a more widely utilized checklist with criteria focused on nonpharmacological studies.
  • The heterogeneity of the study populations limits the broad conclusions that can be drawn.

Additional References:

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  2. Chou R, Deyo R, Friedly J, et al. Nonpharmacologic therapies for low back pain: a systematic review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med 2017; 166: 493–505.
  3. Wong JJ, Cote P, Sutton DA, et al. Clinical practice guidelines for the noninvasive management of low back pain: a systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration. Eur J Pain 2017; 21: 201–216.
  4. Assendelft WJ, Morton SC, Yu EI, et al. Spinal manipulative therapy for low back pain. A meta-analysis of effectiveness relative to other therapies. Ann Intern Med 2003; 138: 871–881.
  5. Merepeza A. Effects of spinal manipulation versus therapeutic exercise on adults with chronic low back pain: a literature review. J Can Chiropr Assoc 2014; 58: 456–466.
  6. Paige NM, Miake-Lye IM, Booth MS, et al. Association of spinal manipulative therapy with clinical benefit and harm for acute low back pain: systematic review and meta-analysis. JAMA 2017; 317: 1451–1460.
  7. Rubinstein SM, Terwee CB, Assendelft WJ, et al. Spinal manipulative therapy for acute low back pain: an update of the Cochrane review. Spine 2013; 38: E158–177.
  8. Rubinstein SM, Terwee CB, Assendelft WJ, et al. Spinal manipulative therapy for acute low back pain: an update of the Cochrane review. Spine 2011; 36: E825–846.
  9. Pickar JG. Neurophysiological effects of spinal manipulation. Spine J 2002; 2: 357–371.
  10. Pickar JG, Bolton PS. Spinal manipulative therapy and somatosensory activation. J Electromyogr Kinesiol 2012; 22: 785–794.
  11. Bialosky JE, Beneciuk JM, Bishop MD, et al. Unraveling the mechanisms of manual therapy: modeling an approach. J Orthop Sports Phys Ther 2017; 48: 8–18.
  12. Bialosky JE, Bishop MD, Price DD, et al. The mechanisms of manual therapy in the treatment of musculoskeletal pain: a comprehensive model. Man Ther 2009; 14: 531–538.
  13. Coronado RA, Gay CW, Bialosky JE, et al. Changes in pain sensitivity following spinal manipulation: a systematic review and meta-analysis. J Electromyogr Kinesiol 2012; 22: 752–767.
  14. Kovanur-Sampath K, Mani R, Cotter J, et al. Changes in biochemical markers following spinal manipulation-a systematic review and meta-analysis. Musculoskelet Sci Pract 2017; 29: 120–131.
  15. Goertz CM, Salsbury SA, Vining RD, et al. Effect of spinal manipulation of upper cervical vertebrae on blood pressure: results of a pilot sham-controlled trial. J Manipulative Physiol Ther 2016; 39: 369–380.
  16. Morgan JP, Dickey JL, Hunt HH, et al. A controlled trial of spinal manipulation in the management of hypertension. J Am Osteopath Assoc 1985; 85: 308–313.
  17. Ward J, Coats J, Tyer K, et al. Immediate effects of anterior upper thoracic spine manipulation on cardiovascular response. J Manipulative Physiol Ther 2013; 36: 101–110.
  18. Ward J, Tyer K, Coats J, et al. Immediate effects of upper thoracic spine manipulation on hypertensive individuals. J Man Manip Ther 2015; 23: 43–50.
  19. Win NN, Jorgensen AMS, Chen YS, et al. 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.
  20. da Silva AC, Marques CMG, Marques JLB. Influence of spinal manipulation on autonomic modulation and heart rate in patients with rotator cuff tendinopathy. J Chiropr Med 2018; 17: 82–89.
  21. Budgell B, Polus B. The effects of thoracic manipulation on heart rate variability: a controlled crossover trial. J Manipulative Physiol Ther 2006; 29: 603–610.
  22. de Bruin ED, Hartmann A, Uebelhart D, et al. Wearable systems for monitoring mobility-related activities in older people: a systematic review. Clin Rehabil 2008; 22: 878–895.
  23. Sillevis R, Cleland J, Hellman M, et al. Immediate effects of a thoracic spine thrust manipulation on the autonomic nervous system: a randomized clinical trial. J Man Manip Ther 2010; 18: 181–190.
  24. Perry J, Green A, Singh S, et al. A preliminary investigation into the magnitude of effect of lumbar extension exercises and a segmental rotatory manipulation on sympathetic nervous system activity. Man Ther 2011; 16: 190–5.
  25. Perry J, Green A, Singh S, et al. A randomised, independent groups study investigating the sympathetic nervous system responses to two manual therapy treatments in patients with LBP. Man Ther 2015; 20: 861–867.
  26. Sampath KK, Botnmark E, Mani R, et al. Neuroendocrine response following a thoracic spinal manipulation in healthy men. J Orthop Sports Phys Ther 2017; 47: 617–627.
  27. Fryer G, Pearce AJ. The effect of lumbosacral manipulation on corticospinal and spinal reflex excitability on asymptomatic participants. J Manipulative Physiol Ther 2012; 35: 86–93.
  28. Groisman S, Silva L, Rocha N, et al. H-reflex responses to highvelocity low-amplitude manipulation in asymptomatic adults. Int J Osteopathic Med 2014; 17: 160–166.
  29. Voerman GE, Gregoric M, Hermens HJ. Neurophysiological methods for the assessment of spasticity: the Hoffmann reflex, the tendon reflex, and the stretch reflex. Disabil Rehabil 2005; 27: 33–68.
  30. Goertz CM, Xia T, Long CR, et al. Effects of spinal manipulation on sensorimotor function in low back pain patients—a randomized controlled trial. Man Ther 2016; 21: 183–190.
  31. Learman KE, Myers JB, Lephart SM, et al. Effects of spinal manipulation on trunk proprioception in subjects with chronic low back pain during symptom remission. J Manipulative Physiol Ther 2009; 32: 118–126.
  32. Evans D. Hierarchy of evidence: a framework for ranking evidence evaluating healthcare interventions. J Clin Nurs 2003; 12: 77–84.
  33. Levels of Evidence. 2009; Available from: 2009/06/oxford-centre-evidence-based-medicine-levels-evidencemarch- 2009/. Accessed October 27, 2018.