RCC Research Bulletins

10th March 2021: Global summit on the efficacy and effectiveness of spinal manipulative therapy for the prevention and treatment of non-musculoskeletal disorders

This recent systematic review investigated the clinical outcomes of SMT, and by implication the notional theory of the mechanism of action of SMT, in non-MSK conditions. The authors made the assumption that this theory was likely to be the same irrespective of the nature of the non-MSK condition and, therefore, that the evidence from clinical studies for different non-MSK conditions could be collated in the final analysis.

Study summary

The study took SMT as including spinal manipulation, mobilisation or traction and addressed two research questions:

  • Compared to sham or placebo interventions, is SMT efficacious for the prevention or management of non-MSK conditions?
  • Compared to other interventions (including sham intervention when delivered in a pragmatic plan of management or no intervention), is SMT effective in the prevention or management of non-MSK conditions?

Strict eligibility criteria included RCT design, and SMT isolated as a single intervention in the treatment arm and not part of multimodal care. The latter criterion was essential to enable investigation of the notional mechanism of SMT action in managing non-MSK conditions. This meant that only 16 RCTs were included in the systematic review, and because trials were further required to meet high or acceptable standards of methodological quality, which was stringently determined, it was considered that the findings of only 6 RCTs constituted the body of evidence across a range of non-MSK conditions, that included:

  • Infantile colic (1 study)
  • Childhood asthma (1 study)
  • Hypertension (2 studies)
  • Primary dysmenorrhoea (1 study)
  • Migraine (1 study)

When the findings of these 6 trials were considered, the authors found no evidence of an effect of SMT for the prevention or management of non-MSK disorders.  This consistent finding across multiple studies lead to the conclusion that the current best evidence does not support SMT  as an intervention for non-MSK conditions and challenged the theory that treating spinal dysfunctions with SMT can influence organs and their function.

Commentary points

This expertly conducted study followed a rigorous and transparent process to address its research questions. There are however some limitations in what can be inferred from its findings:

Evidence for management of individual non-MSK conditions

This study did not have a stated aim to evaluate the efficacy or effectiveness of SMT on any individual non-MSK condition, yet did draw conclusions about these. The best available evidence for most of the individual conditions highlighted consisted of only 1 RCT and, based upon such a limited quantity of evidence, conclusions regarding individual conditions are therefore less certain and more susceptible to being changed should new evidence emerge.

A reductionist approach

The effect of SMT was evaluated in isolation from the more usual clinical approach that utilises a package of care and so may not reflect the way patients are actually managed in a clinical setting. Additional interventions that may be included and contextual effects can have significant effects on patient outcomes.

Absence of evidence is not evidence of no effect

The authors’ conclusion that there is no evidence of an effect of SMT in the management of non-MSK conditions may well be valid, but another, more cautious interpretation would be that, currently, there is an absence of acceptable quality evidence.

Future research

The authors recognised the limitations of their study and call for further research. To be included in an updated systematic review such as this would require new, high quality RCTs investigating SMT as an isolated intervention. However, the limitation of such studies is that they may bear little resemblance to the management of conditions in the real world of clinical practice, where a package of care approach is utilised. While high methodological quality is paramount, research that is clinically relevant, inclusive and can be applied to clinical practice is also needed to usefully inform evidence-based care. PDF

23 March 2020: Spinal manipulation and the immune system

The question of whether spinal manipulation has an effect on the immune system has been the subject of a small number of studies identified by three reviews across the subject [1,2,3].

Studies investigating the effects of spinal manipulation on immunoregulatory cells and molecules

Four primary studies have investigated the effects, in healthy individuals, of spinal manipulation, compared with sham or comparison interventions, on cells and secreted molecules with roles in immunoregulatory function (Substance P, regulatory T cells, interleukin-2, interleukin-2 regulated antibodies and Tumour Necrosis Factor (TNF)). These cellular/molecular responses were measured in isolated in vitro systems [4-7]. The studies reported some effects, however these were contradictory, and it is not known what clinical relevance, if any, these effects have (see explanation below).

A further RCT investigated responses in HIV positive patients to upper cervical adjustments. This study had ten patients, equally divided between treatment and the control groups. No significant difference in blood CD4 cell counts were observed in the treatment group compared to the control group [8].

The difficulty in interpreting reported in vitro cellular/molecular responses are clearly demonstrated by the findings for altered TNF in two studies. One study (with no control group) found increased TNF levels after SMT [9], however another reported decreased TNF levels measured at a different time point [5].

Immune cellular/molecular responses are highly complex, differing over time and having different and sometimes opposing effects in physiological (healthy function) versus pathological states [10]. In the case of TNF, increased levels can have putatively beneficial effects on the activation of regulatory T cells. However, its effects can also be detrimental; TNF is a pro-inflammatory cytokine that causes apoptosis in tumour/cancer cells [10]. This clearly illustrates the fact that in vitro findings cannot be extrapolated to clinical effects.

There have been no reported systematic evaluations of the quality of any of the studies described above.

Clinical trials of pro-immune effects of spinal manipulation

There is no available evidence from clinical trials investigating effectiveness of spinal manipulation on improving patients’ immunity to contracting infectious disease.

Two studies that have been widely quoted as providing evidence of such effects either cannot be found [11] or constituted narrative accounts of historic events over 100 years ago that cannot be corroborated [12]. Thus, there is no available scientific evidence that would permit valid claims to be made for spinal manipulation conferring or enhancing immunity.

Key point summary

  • There are no clinical trials of the effectiveness of SMT on enhancing immunity to infectious diseases
  • 3 out of 4 studies report various cellular/molecular responses to SMT in vitro, however these are contradictory and offer no evidence of an overall likely pro-immune, clinically-relevant effect in patients
  • There has been no systematic appraisal of the quality of the studies in this field
  • There is no evidence that would reach the threshold of the Advertising Standard Agency (ASA) for enabling claims to be made for effectiveness of spinal manipulation on immunity


  1. Bolton PS, Budgell B (2012) Visceral responses to spinal manipulation. J Electromyogr Kinesiol 22(5): p. 777-84.
  2. Colombi A, Testa M (2019) The effects induced by spinal manipulative therapy on the immune andendocrine systems. Medicina 53:448. doi 10.3390/medicina55080448. Medicina 53:448, DOI: 10.3390/medicina55080448.
  3. World Federation of Chiropractic (2020) The Effect of Spinal Adjustment / Manipulation on Immunity and the Immune System: A Rapid Review of Relevant Literature.
  4. Brennan PC et al (1991) Enhanced phagocytic cell respiratory burst induced by spinal manipulation: potential role of substance P. J Manipulative Physiol Ther 14(7): p. 399-408.
  5. Teodorczyk-Injeyan JA et al (2006) Spinal manipulative therapy reduces inflammatory cytokines but not substance P production in normal subjects. J Manipulative Physiol Ther. 29(1): p. 14-21.
  6. Teodorczyk-Injeyan JA et al (2008) Enhancement of in vitro interleukin-2 production in normal subjects following a single spinal manipulative treatment. Chiropr Osteopat 16: p. 5.
  7. Teodorczyk-Injeyan JA et al (2010) Interleukin 2-regulated in vitro antibody production following a single spinal manipulative treatment in normal subjects. Chiropr Osteopat 18: p. 26.
  8. Selano J et al (1994) Effects of Specific Upper Cervical Adjustments on the CD4 Counts of HIV Positive Patients. Chiropractic Research Journal 3(1): p. 32-39.
  9. Brennan PC et al (1992) Enhanced neutrophil respiratory burst as a biological marker for manipulation forces: duration of the effect and association with substance P and tumor necrosis factor. J Manipulative Physiol Ther 15(2): p. 83-9.
  10. Zhang L, Yao CH (2016) The Physiological Role of Tumor Necrosis Factor in Human Immunity and Its Potential Implications in Spinal Manipulative Therapy: A Narrative Literature Review. J Chiropr Med 15(3): p. 190-6.
  11. Pero R (1989) “Medical Researcher Excited By CBSRF Project Results.” The Chiropractic Journal, August 1989; 32.
  12. Smith RK (1920) One hundred thousand cases of influenza with a death rate of one-fortieth of that officially reported under conventional medical treatment [reprint of J Am Osteopath Assoc. 19:172-175]. J Am Osteopath Assoc. 2000; 100: 320-323.

Comparative effectiveness of spinal manipulation for sciatica

In 2006, Santilli et al reported that, compared with sham manipulation, active spinal manipulation is more effective at six months at relieving local or radiating pain in people with acute back pain and sciatica with disc protrusion. A recent network meta-analysis of the many different treatment strategies (Lewis et al, 2015) has now concluded that spinal manipulation is one of a number of interventions that provides significant improvement for sciatica compared to inactive control or conservative therapy. The other effective interventions include acupuncture, non-opioid analgesia, epidural injections and surgery. Note that an earlier cohort study demonstrated similar clinical effectiveness and a cost benefit of employing spinal manipulation as opposed to nerve root injections for patients with symptomatic MRI-confirmed lumbar disc herniation (Peterson et al, 2013).


Lewis RA et al (2015) Comparative clinical effectiveness of management strategies for sciatica: systematic review and network meta-analyses. The Spine Journal 15, 1461–1477.

Peterson C et al (2013) Symptomatic magnetic resonance imaging-confirmed lumbar disc herniation patients: A comparative effectiveness prospective observational study of 2 age- and sex-matched cohorts treated with either high-velocity, low-amplitude spinal manipulative therapy or imaging-guided lumbar nerve root injections. Journal of Manipulative and Physiological Therapeutics219, 36(4), 218-225.

Santilli V et al (2006) Chiropractic manipulation in the treatment of acute back pain and sciatica with disc protrusion: a randomized double-blind clinical trial of active and simulated spinal manipulations. The Spine Journal 6, 131–137.

Cost effectiveness of manual therapy

A systematic review of the cost-effectiveness of manual therapy for musculoskeletal pain, funded by the Royal College of Chiropractors, was recently published in the Journal of Manipulative and Physiological Therapeutics. The conclusions of the review were positive for the cost-effectiveness of manual therapy approaches to management of low back and shoulder pain, but found inconsistent results for management of neck pain. The full article can be read here.

Cost-effectiveness studies evaluate only the direct costs of provision of the care received and the review highlights some limitations in the available evidence, including the fact that more extensive economic evaluations (that would include the longer term costs and/or savings in healthcare) have not been conducted. Consequently the RCC recognises economic evaluation studies as one of the research priorities for chiropractic.

This study was part of the wide-ranging independent evaluation of manual therapy that the RCC commissioned to be conducted by Warwick Evidence, a research group that have been involved in clinical guideline development for NICE. An earlier publication in Chiropractic and Manual Therapies (Clar et al, 2014) reported some of the findings of their review of the clinical effectiveness of manual therapy approaches for different conditions. The full report produced by Warwick Evidence can be found here (Sutcliffe et al, 2012).

Cervical Artery Dissection and Cervical Spinal Manipulation

The RCC’s Research Committee has highlighted a recent review article from the American Heart Association Stroke Council (Biller et al, 2014) that provides a scientific statement for healthcare professionals of the current state of evidence on the diagnosis and management of vertebral and carotid artery dissections and of their statistical association with cervical manipulative therapy.

The article, published in Stroke, was produced by a multidisciplinary writing group that included a chiropractor. The article, which can be accessed in full here makes important reading for any chiropractor as it provides the most up to date evidence summary for cervical artery dissections, that includes:

  • The incidence, aetiology and pathology of cervical artery dissections
  • A comprehensive list of risk factors that should be considered during pre-treatment screening
  • Characterisations of the signs and symptoms that may be present in a patient in whom either a vertebral or a carotid artery dissection is underway
  • Information on diagnosis and investigations
  • Information on medical management, clinical outcomes and prognosis

In relation to the association between cervical manipulative therapy and cervical artery dissection, it is acknowledged that this may be performed by chiropractors, osteopaths, physical therapists or allopathic medical professionals. Evidence relating to the biomechanics of cervical manipulation and possible mechanisms of cervical artery dissections is reviewed. The article critically reviews the findings of case-control studies, concluding that:

  • A few studies suggest an association between cervical manipulative therapy and cervical artery dissection, but did not distinguish whether thrust techniques were involved.
  • The best available evidence suggests cervical artery dissection, particularly vertebral artery dissection, may be of a low incidence but could be a serious complication of cervical manipulative therapy
  • A single study reported a similar association of vertebral artery dissection with chiropractic visits as with primary care physician visits, thus the association may not be causal
  • Increased education of providers of cervical manipulative therapy may be warranted to improve diagnosis of cervical artery dissection
  • Patients with neck pain should be informed of the potential risks and benefits of receiving cervical manipulative therapy and practitioners should carefully consider cervical artery dissection prior to performing cervical manipulation