Background and Objective: Heart rate variability (HRV) as an index of the autonomic nervous system appears to be related to reactivity to experimental pain stimuli. HRV could better explain the contributions of sympathetic and parasympathetic activity response to nociceptive stimulation. The aim of this study was to systematically review and synthesize the current evidence on HRV in relation to the experience of pain in experimental tasks. Databases and Data Treatment: Studies indexed in the PubMed, PsycINFO, MEDLINE, WebOfScience, and Scopus databases were reviewed for eligibility. Studies on the autonomic response (i.e., HRV) to experimentally induced pain in healthy adults were included. Different methods of pain induction were considered (e.g., thermal, pressure, and electrical). Data were synthesized considering the association between HRV and both pain induction and subjective measures of pain. Results: Seventy-one studies were included. The results underline significant change in both the sympathetic and parasympathetic autonomic nervous systems during the painful stimulation independent of the pain induction method. The autonomic reaction to pain could be affected by several factors, such as sex, age, body mass index, breathing patterns, the intensity of the stimulation, and the affective state. Moreover, an association between the autonomic nervous system and the subjective experience of pain was found. Higher parasympathetic activity was associated with better self-regulation capacities and, accordingly, a higher pain inhibition capacity. Conclusions: HRV appears to be a helpful marker to evaluate nociceptive response in experimentally induced pain. Future studies are also needed in clinical samples to understand better the interindividual changes of autonomic response due to pain stimuli.

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Heart Rate Variability and Pain: A Systematic Review

BACKGROUND CONTEXT Mobilization and manipulation therapies are widely used to benefit patients with chronic low back pain. However, questions remain about their efficacy, dosing, safety, and how these approaches compare with other therapies. PURPOSE The present study aims to determine the efficacy, effectiveness, and safety of various mobilization and manipulation therapies for treatment of chronic low back pain. STUDY DESIGN/SETTING This is a systematic literature review and meta-analysis. OUTCOME MEASURES The present study measures self-reported pain, function, health-related quality of life, and adverse events. METHODS We identified studies by searching multiple electronic databases from January 2000 to March 2017, examining reference lists, and communicating with experts. We selected randomized controlled trials comparing manipulation or mobilization therapies with sham, no treatment, other active therapies, and multimodal therapeutic approaches. We assessed risk of bias using Scottish Intercollegiate Guidelines Network criteria. Where possible, we pooled data using random-effects meta-analysis. Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was applied to determine the confidence in effect estimates. This project is funded by the National Center for Complementary and Integrative Health under Award Number U19AT007912. RESULTS Fifty-one trials were included in the systematic review. Nine trials (1,176 patients) provided sufficient data and were judged similar enough to be pooled for meta-analysis. The standardized mean difference for a reduction of pain was SMD=−0.28, 95% confidence interval (CI) −0.47 to −0.09, p=.004; I2=57% after treatment; within seven trials (923 patients), the reduction in disability was SMD=−0.33, 95% CI −0.63 to −0.03, p=.03; I2=78% for manipulation or mobilization compared with other active therapies. Subgroup analyses showed that manipulation significantly reduced pain and disability, compared with other active comparators including exercise and physical therapy (SMD=−0.43, 95% CI −0.86 to 0.00; p=.05, I2=79%; SMD=−0.86, 95% CI −1.27 to −0.45; p<.0001, I2=46%). Mobilization interventions, compared with other active comparators including exercise regimens, significantly reduced pain (SMD=−0.20, 95% CI −0.35 to −0.04; p=.01; I2=0%) but not disability (SMD=−0.10, 95% CI −0.28 to 0.07; p=.25; I2=21%). Studies comparing manipulation or mobilization with sham or no treatment were too few or too heterogeneous to allow for pooling as were studies examining relationships between dose and outcomes. Few studies assessed health-related quality of life. Twenty-six of 51 trials were multimodal studies and narratively described. CONCLUSION There is moderate-quality evidence that manipulation and mobilization are likely to reduce pain and improve function for patients with chronic low back pain; manipulation appears to produce a larger effect than mobilization. Both therapies appear safe. Multimodal programs may be a promising option.

Manipulation and Mobilization for Treating Chronic Low Back Pain

Manipulation-induced hypoalgesia (MIH) represents reduced pain sensitivity following joint manipulation, and has been documented in various populations. It is unknown, however, whether MIH following high-velocity low-amplitude spinal manipulative therapy is a specific and clinically relevant treatment effect. This systematic critical review with meta-analysis investigated changes in quantitative sensory testing measures following high-velocity low-amplitude spinal manipulative therapy in musculoskeletal pain populations, in randomised controlled trials. Our objectives were to compare changes in quantitative sensory testing outcomes after spinal manipulative therapy vs. sham, control and active interventions, to estimate the magnitude of change over time, and to determine whether changes are systemic or not. Fifteen studies were included. Thirteen measured pressure pain threshold, and four of these were sham-controlled. Change in pressure pain threshold after spinal manipulative therapy compared to sham revealed no significant difference. Pressure pain threshold increased significantly over time after spinal manipulative therapy (0.32 kg/cm2, CI 0.22–0.42), which occurred systemically. There were too few studies comparing to other interventions or for other types of quantitative sensory testing to make robust conclusions about these. We found that systemic MIH (for pressure pain threshold) does occur in musculoskeletal pain populations, though there was low quality evidence of no significant difference compared to sham manipulation. Future research should focus on the clinical relevance of MIH, and different types of quantitative sensory tests. Prospectively registered with PROSPERO (registration CRD42016041963
 ).

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Manipulation-induced hypoalgesia in musculoskeletal pain populations: a systematic critical review and meta-analysis

Background Changes in quantitative sensory tests have been observed after spinal manipulative therapy (SMT), particularly in pressure pain thresholds (PPT) and temporal summation (TS). However, a recent systematic review comparing SMT to sham found no significant difference in PPT in patients with musculoskeletal pain. The sham-controlled studies were generally low quality, and conclusions about other quantitative sensory tests could not be made. Objectives We aimed to perform a sham-controlled study with the specific objective of investigating changes in PPT and TS short-term after lumbar SMT compared to sham manipulation in people with low back pain. Methods This was a double-blind randomised controlled trial comparing high-velocity low-amplitude lumbar SMT against sham manipulation in participants with low back pain. Primary outcome measures were PPT at the calf, lumbar spine and shoulder, and TS at the hands and feet. These were measured at baseline, then immediately, 15 min and 30 min post-intervention. Results Eighty participants (42 females) were included in the analyses (mean age 37 years), with 40 participants allocated to each intervention group. Significant between-group differences were only observed for calf PPT, which could be explained by a decrease in PPT (increased sensitivity) after SMT and an increase after sham. Feet TS decreased significantly over time after both SMT and sham, and any other changes over time were inconsistent. Conclusions Our results suggest that lumbar SMT does not have a short-term hypoalgesic effect, as measured with PPT and TS, when compared to sham manipulation in people with low back pain.

No difference in pressure pain threshold and temporal summation after lumbar spinal manipulation compared to sham: A randomised controlled trial in adults with low back pain.

A small proportion of chiropractors, osteopaths, and other manual medicine providers use spinal manipulative therapy (SMT) to manage non-musculoskeletal disorders. However, the efficacy and effectiveness of these interventions to prevent or treat non-musculoskeletal disorders remain controversial. We convened a Global Summit of international scientists to conduct a systematic review of the literature to determine the efficacy and effectiveness of SMT for the primary, secondary and tertiary prevention of non-musculoskeletal disorders. The Global Summit took place on September 14–15, 2019 in Toronto, Canada. It was attended by 50 researchers from 8 countries and 28 observers from 18 chiropractic organizations. At the summit, participants critically appraised the literature and synthesized the evidence. We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health, and the Index to Chiropractic Literature from inception to May 15, 2019 using subject headings specific to each database and free text words relevant to manipulation/manual therapy, effectiveness, prevention, treatment, and non-musculoskeletal disorders. Eligible for review were randomized controlled trials published in English. The methodological quality of eligible studies was assessed independently by reviewers using the Scottish Intercollegiate Guidelines Network (SIGN) criteria for randomized controlled trials. We synthesized the evidence from articles with high or acceptable methodological quality according to the Synthesis without Meta-Analysis (SWiM) Guideline. The final risk of bias and evidence tables were reviewed by researchers who attended the Global Summit and 75% (38/50) had to approve the content to reach consensus. We retrieved 4997 citations, removed 1123 duplicates and screened 3874 citations. Of those, the eligibility of 32 articles was evaluated at the Global Summit and 16 articles were included in our systematic review. Our synthesis included six randomized controlled trials with acceptable or high methodological quality (reported in seven articles). These trials investigated the efficacy or effectiveness of SMT for the management of infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. None of the trials evaluated the effectiveness of SMT in preventing the occurrence of non-musculoskeletal disorders. Consensus was reached on the content of all risk of bias and evidence tables. All randomized controlled trials with high or acceptable quality found that SMT was not superior to sham interventions for the treatment of these non-musculoskeletal disorders. Six of 50 participants (12%) in the Global Summit did not approve the final report. Our systematic review included six randomized clinical trials (534 participants) of acceptable or high quality investigating the efficacy or effectiveness of SMT for the treatment of non-musculoskeletal disorders. We found no evidence of an effect of SMT for the management of non-musculoskeletal disorders including infantile colic, childhood asthma, hypertension, primary dysmenorrhea, and migraine. This finding challenges the validity of the theory that treating spinal dysfunctions with SMT has a physiological effect on organs and their function. Governments, payers, regulators, educators, and clinicians should consider this evidence when developing policies about the use and reimbursement of SMT for non-musculoskeletal disorders.

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The global summit on the efficacy and effectiveness of spinal manipulative therapy for the prevention and treatment of non-musculoskeletal disorders: a systematic review of the literature

Spinal manipulation (SM) has been shown to have an effect on pain perception. More knowledge is needed on this phenomenon and it would be relevant to study its effect in asymptomatic subjects. To compare regional effect of SM on pressure pain threshold (PPT) vs. sham, inactive control, mobilisation, another SM, and some type of physical therapy. In addition, we reported the results for the three different spinal regions. A systematic search of literature was done using PubMed, Embase and Cochrane. Search terms were ((spinal manipulation) AND (experimental pain)); ((spinal manipulative therapy OR spinal manipulation) AND ((experimental pain OR quantitative sensory testing OR pressure pain threshold OR pain threshold)) (Final search: June 13th 2017). The inclusion criteria were SM performed anywhere in the spine; the use of PPT, PPT tested in an asymptomatic region and on the same day as the SM. Studies had to be experimental with at least one external or internal control group. Studies on only spinal motion or tenderness, other reviews, case reports, and less than 15 invited participants in each group were excluded. Evidence tables were constructed with information relevant to each research question and by spinal region. Results were reported in relation to statistical significance and were interpreted taking into account their quality. Only 12 articles of 946 were accepted. The quality of studies was generally good. In 8 sham controlled studies, a psychologically and physiologically “credible” sham was found in only 2 studies. A significant difference was noted between SM vs. Sham, and between SM and an inactive control. No significant difference in PPT was found between SM and another SM, mobilisation or some type of physical therapy. The cervical region more often obtained significant findings as compared to studies in the thoracic or lumbar regions. SM has an effect regionally on pressure pain threshold in asymptomatic subjects. The clinical significance of this must be quantified. More knowledge is needed in relation to the comparison of different spinal regions and different types of interventions.

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The regional effect of spinal manipulation on the pressure pain threshold in asymptomatic subjects: a systematic literature review

The autonomic nervous system interacts with the pain system. Knowledge on the effects of high velocity low amplitude spinal manipulations (SM) on autonomic activity and experimentally induced pain is limited. In particular, the effects of SM on autonomic activity and pain beyond the immediate post intervention period as well as the relationship between these two outcomes are understudied. Thus, new research is needed to provide further insight on this issue. The aim was to assess the effect of a single SM (i.e. SM vs. sham) on cardiovascular autonomic activity. Also, we assessed the relationship between cardiovascular autonomic activity and level of pain threshold after the interventions. We conducted a randomized, cross-over, sham-controlled trial on healthy first-year chiropractic students comprising two experimental sessions separated by 48 h. During each session, subjects received, in a random order, either a thoracic SM or a sham manipulation. Cardiovascular autonomic activity was assessed using heart rate and systolic blood pressure variabilities. Pain sensitivity was assessed using pressure pain threshold. Measurements were performed at baseline and repeated three times (every 12 min) during the post intervention period. Participants and outcome assessors were blinded. The effect of the SM was tested with linear mixed models. The relationship between autonomic outcomes and pressure pain threshold was tested with bivariate correlations. Fifty-one participants were included, forty-one were finally analyzed. We found no statistically significant difference between SM and sham in cardiovascular autonomic activity post intervention. Similarly, we found no post-intervention relationship between cardiovascular autonomic activity and pressure pain threshold. Our results suggest that a single SM of the thoracic spine has no specific effect on cardiovascular autonomic activity. Also, we found no relationship between cardiovascular autonomic activity and pressure pain threshold after the SM. Further experimental research should consider the use of several markers of autonomic activity and a more comprehensive pain assessment. N° NCT03273868. Registered September 6, 2017.

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The effect of a single spinal manipulation on cardiovascular autonomic activity and the relationship to pressure pain threshold: a randomized, cross-over, sham-controlled trial

Spinal manipulation (SM) has been shown in a systematic review to have a statistically significant effect on the pressure pain threshold (PPT) in asymptomatic subjects, when SM is compared to a sham intervention. The magnitude and duration of this effect is unclear. To determine the effect-size of SM in asymptomatic subjects and its duration. This is a secondary analysis of data from a previous review. We sought to compare the effect-sizes in the various articles but had to calculate them ourselves, at different follow-up time measurements. Effect-sizes (Cohen’s d or Hedge’s g coefficient) were considered low, medium, and large, at the cut points of 0.2, 0.5, and 0.8, respectively. Effect-sizes were reported in 6/8 studies, but all had calculated ‘within-group’ changes, not ‘between-group’ differences. Immediately after SM, only one study of four (with four measurements) had a statistically significant ‘medium’ effect size (d = 0.56; 95% CI: 00.4–1.08 to d = 0.70; 95% CI:0.18–1.22). Five minutes after SM, 4/5 studies found a statistically significant ‘medium to large’ effect-size (d = 0.51; 95% CI: 0.04–0.98 to d = 1.24; 95% CI: 0.28–2.20). Ten minutes after SM, two studies reported a ‘medium’ effect-size with statistical significance (d = 0.58; 95% CI: 0.11–1.05 to d = 0.80; 95% CI: 0.12–1.48). We drew no conclusions for the effect-sizes at one minute and thirty minutes after SM, as no between-group statistical difference was found. Authors need to revise their approach to ‘effect size’. Our calculations showed that the effect-size of SM on PPT may go from ‘medium’ to ‘large’ within the first five minutes but appears to diminish again within ten minutes. Research of this type should collect information for longer periods and compare results to other interventions to put results into perspective.

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How big is the effect of spinal manipulation on the pressure pain threshold and for how long does it last? - secondary analysis of data from a systematic review.

Spinal manipulation (SM) has been shown to have an effect on the pressure pain threshold (PPT) in asymptomatic subjects, but SM has never been compared in studies on this topic to a validated sham procedure. We investigated the effect of SM on the PPT when measured i) in the area of intervention and ii) in an area remote from the intervention. In addition, we measured the size and duration of the effect. In a randomized cross-over trial, 50 asymptomatic chiropractic students had their PPT measured at baseline, immediately after and every 12 min after intervention, over a period of 45 min, comparing values after SM and a previously validated sham. The trial was conducted during two sessions, separated by 48 h. PPT was measured both regionally and remotely from the ‘treated’ thoracic segment. Blinding of study subjects was tested with a post-intervention questionnaire. We used mixed linear regression with the baseline value and time as co-variates. If a significant difference were found between groups, then an effect size would be calculated using Cohen’s d or Hedge’s h coefficient. Statistical significance was set at p < 0.05. Study subjects had been successfully blinded. No statistically significant differences were found between SM and sham estimates, at any time or anatomical location. When compared to a valid sham procedure and with successfully blinded subjects, there is no regional or remote effect of spinal manipulation of the thoracic spine on the pressure pain threshold in a young pain-free population.

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What is the effect of spinal manipulation on the pressure pain threshold in young, asymptomatic subjects? A randomized placebo-controlled trial, with a cross-over design.

Margaux Honoré

Papers

The regional effect of spinal manipulation on the pressure pain threshold in asymptomatic subjects: a systematic literature review

The effect of a single spinal manipulation on cardiovascular autonomic activity and the relationship to pressure pain threshold: a randomized, cross-over, sham-controlled trial

How big is the effect of spinal manipulation on the pressure pain threshold and for how long does it last? - secondary analysis of data from a systematic review.

What is the effect of spinal manipulation on the pressure pain threshold in young, asymptomatic subjects? A randomized placebo-controlled trial, with a cross-over design.