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Abstract

To examine the effect of a single spinal manipulation therapy (SMT) on the in vitro production of inflammatory cytokines, tumor necrosis factor alpha, and interleukin (IL) 1beta, in relation to the systemic (in vivo) levels of neurotransmitter substance P (SP). Sixty-four asymptomatic subjects were assigned to SMT, sham manipulation, or venipuncture control group. SMT subjects received a single adjustment in the thoracic spine. Blood and serum samples were obtained from subjects before and then at 20 minutes and 2 hours after intervention. Whole-blood cultures were activated with lipopolysaccharide (LPS) for 24 hours. Cytokine production in culture supernatants and serum SP levels were assessed by specific immunoassays. Over the study period, a significant proportion (P </= .05) of sham and control subjects demonstrated progressive increases in the synthesis of tumor necrosis factor alpha and IL-1beta. Conversely, in a comparable proportion of cultures from SMT-derived subjects, the production of both cytokines decreased gradually. Normalization of the observed alterations to reflect the changes relative to self-baselines demonstrated that, within 2 hours after intervention, the production of both cytokines increased significantly (P < .001 to .05) in both controls. In contrast, a significant (P < .001 to .05) reduction of proinflammatory cytokine secretion was observed in cultures from SMT-receiving subjects. In all study groups, serum levels of SP remained unaltered within 2 hours after intervention. SMT-treated subjects show a time-dependent attenuation of LPS-induced production of the inflammatory cytokines unrelated to systemic levels of SP. This suggests SMT-related down-regulation of inflammatory-type responses via a central yet unknown mechanism.
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... For both manipulative and exercise therapy, multiple potential mechanisms for pain relief have been proposed (Gevers-Montoro et al., 2021a;Wun et al., 2021). The specific mechanisms are still unknown, but human and animal studies have shown a correlation between SMT and a decrease in serum levels and in vitro production of pro-inflammatory mediators, including TNF-α (Teodorczyk-Injeyan et al., 2006Roy et al., 2010;Song et al., 2016). Similarly, investigations on the mechanisms of exercise therapy for CLBP have also found that a reduction in levels of the same cytokine network may be involved in pain relief associated to exercise therapy (Cheng et al., 2015;Leung et al., 2016;James et al., 2018a). ...
... Data on a potential influence of SMT on proinflammatory cytokines including TNF-α is still scarce. Teodorczyk-Injeyan et al. (2006) collected blood samples of asymptomatic subjects randomly assigned to either SMT, sham SMT or venipuncture control groups. Blood cultures were stimulated with lipopolysaccharide to induce in vitro production of proinflammatory cytokines for 24 h. ...
... Blood cultures were stimulated with lipopolysaccharide to induce in vitro production of proinflammatory cytokines for 24 h. The study showed a time-dependent significant attenuation of the in vitro production of inflammatory cytokines (including TNF-α) in the SMT group (Teodorczyk-Injeyan et al., 2006). More recently, the same group reported significantly higher in vitro TNF-α production in acute TABLE 3 | Before and after treatment variations in TNF-α concentrations, pain intensity and disability in patients following or not following a home exercise program, and using or not using pain medication during the study. ...
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Background and aims: Low back pain is the leading cause of years lived with disability worldwide. Chiropractors employ different interventions to treat low back pain, including spinal manipulative therapy, although the mechanisms through which chiropractic care improves low back pain are still unclear. Clinical research and animal models suggest that spinal manipulation might modulate plasma levels of inflammatory cytokines, which have been involved in different stages of low back pain. More specifically, serum levels of Tumor Necrosis Factor-alpha (TNF-α) have been found to be elevated in patients with chronic low back pain. We aimed to investigate whether urine from chronic low back pain patients could be an appropriate medium to measure concentrations of TNF-α and to examine possible changes in its levels associated to chiropractic care. Methods: Urine samples were collected from 24 patients with chronic low back pain and TNF-α levels were analyzed by ELISA before and after 4–6 weeks of care compared to a reference value obtained from 5 healthy control subjects, by means of a Welch’s t-test. Simultaneously, pain intensity and disability were also evaluated before and after care. Paired t-tests were used to compare mean pre and post urinary concentrations of TNF-α and clinical outcomes. Results: Significantly higher baseline levels of urinary TNF-α were observed in chronic low back pain patients when compared to our reference value (p < 0.001), which were significantly lower after the period of chiropractic treatment (p = 0.03). Moreover, these changes were accompanied by a significant reduction in pain and disability (both p < 0.001). However, levels of urinary TNF-α were not correlated with pain intensity nor disability. Conclusion: These results suggest that urine could be a good milieu to assess TNF-α changes, with potential clinical implications for the management of chronic low back pain.
... 68 In a small study by Selano and Grostic, it was found that upper cervical adjustments increased CD4 helper T-cell counts by 48 percent over the six-month duration of the study. 69 Teodorczyk-Injeyan showed that chiropractic treated subjects have also shown attenuation of lipopolysaccharide induced production of the inflammatory cytokines unrelated to systemic levels of the neurotransmitter substance P. 70 Research has explored the relationship of spinal manipulation, spino-autonomic reflexes and their influence on activity of immune and inflammatory cells. This research has shown a reduction in pro-inflammatory cytokines after spinal manipulation. ...
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A growing body of evidence supports our understanding of the role of the nervous system in immune system function. Basic science studies and clinical reports in the scientific literature provide supportive evidence of the beneficial effects of chiropractic care in improving function, including immune system function and quality of life. These guidelines support chiropractic practice in an evidence-informed, patient centered model. Evidence-informed practice involves the integration of the knowledge and experience of the chiropractor, the best available research evidence, and the needs and preferences of individual patients. Furthermore, chiropractors must be free to discuss, publish, and otherwise disseminate the best available evidence, and in practice, apply it to the needs of individual patients.
... However, most practitioners anecdotally believe that the popping sounds are an indicator of the successful delivery of SM, explaining why researchers often repeat SM when the popping sound is not elicited on the first attempt [10,66,[74][75][76][77][78][79][80][81][82]. In addition, some studies have observed preliminary evidence that suggests a greater hypoalgesic effect (i.e., perhaps associated with proinflammatory cytokine secretion, temporal sensory summation, and/or supraspinal mechanisms) in subjects that experienced audible popping [73,83,84]. Although no firm conclusions can be drawn about the clinical relevance, when the popping sound was a requirement in the methods, SM was found more effective in reducing short-term pain and disability than non-thrust mobilization (i.e., no audible popping sound) [74,82]. ...
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Background and Objective High-velocity low-amplitude thrust spinal manipulation (SM) is a recommended and commonly used manual therapy intervention in physiotherapy. Beliefs surrounding the safety and effectiveness of SM have challenged its use, and even advocated for its abandonment. Our study aimed to investigate the knowledge and beliefs surrounding SM by Italian physiotherapists compared with similar practitioners in other countries. Methods An online survey with 41 questions was adapted from previous surveys and was distributed via a mailing list of the Italian Physiotherapists Association (March 22–26, 2020). The questionnaire was divided into 4 sections to capture information on participant demographics, utilization, potential barriers, and knowledge about SM. Questions were differentiated between spinal regions. Attitudes towards different spinal regions, attributes associated with beliefs, and the influence of previous educational background were each evaluated. Results Of the 7398 registered physiotherapists, 575 (7.8%) completed the survey and were included for analysis. The majority of respondents perceived SM as safe and effective when applied to the thoracic (74.1%) and lumbar (72.2%) spines; whereas, a smaller proportion viewed SM to the upper cervical spine (56.8%) as safe and effective. Respondents reported they were less likely to provide and feel comfortable with upper cervical SM (respectively, 27.5% and 48.5%) compared to the thoracic (respectively, 52.2% and 74.8%) and lumbar spines (respectively, 46.3% and 74.3%). Most physiotherapists (70.4%) agreed they would perform additional screening prior to upper cervical SM compared to other spinal regions. Respondents who were aware of clinical prediction rules were more likely to report being comfortable with SM (OR 2.38–3.69) and to perceive it as safe (OR 1.75–3.12). Finally, physiotherapists without musculoskeletal specialization, especially those with a traditional manual therapy background, were more likely to perform additional screening prior to SM, use SM less frequently, report being less comfortable performing SM, and report upper cervical SM as less safe ( p < 0.001). Discussion The beliefs and attitudes of physiotherapists surrounding the use of SM are significantly different when comparing the upper cervical spine to other spinal regions. An educational background in traditional manual therapy significantly influences beliefs and attitudes. We propose an updated framework on evidence-based SM.
... Based on the sample size calculation 52 (longitudinal analysis; three time points (baseline, immediately follow-up, 2 hours follow-up) with 80% power to detect a mean difference of 550 (SD 933) for TNF-α levels with a 0.05 two-sided significance level, correlation of 0.6 among repeated measures, ratio between groups of 0.25, a total sample size of 91 is needed. 27 Allowing for a drop-out rate of ~10%, a total sample size of 100 participants is required. ...
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Introduction Joint mobilisation and manipulation often results in immediate pain relief in people with neck pain. However, the biological mechanisms behind pain relief are largely unknown. There is preliminary evidence that joint mobilisation and manipulation lessens the upregulated neuroimmune responses in people with persistent neck pain. Methods and analysis This study protocol describes a randomised placebo-controlled trial to investigate whether joint mobilisation and manipulation influence neuroimmune responses in people with persistent neck pain. People with persistent neck pain (N=100) will be allocated, in a randomised and concealed manner, to the experimental or control group (ratio 3:1). Short-term (ie, baseline, immediately after and 2 hours after the intervention) neuroimmune responses will be assessed, such as inflammatory marker concentration following in vitro stimulation of whole blood cells, systemic inflammatory marker concentrations directly from blood samples, phenotypic analysis of peripheral blood mononuclear cells and serum cortisol. Participants assigned to the experimental group (N=75) will receive cervical mobilisations targeting the painful and/or restricted cervical segments and a distraction manipulation of the cervicothoracic junction. Participants assigned to the control group (N=25) will receive a placebo mobilisation and placebo manipulation. Using linear mixed models, the short-term neuroimmune responses will be compared (1) between people in the experimental and control group and (2) within the experimental group, between people who experience a good outcome and those with a poor outcome. Furthermore, the association between the short-term neuroimmune responses and pain relief following joint mobilisation and manipulation will be tested in the experimental group. Ethics and dissemination This trial is approved by the Medical Ethics Committee of Amsterdam University Medical Centre, location VUmc (Approval number: 2018.181). Trial registration number NL6575 (trialregister.nl
... Various mechanisms of how MT affects neurobiology have been hypothesised by different researchers, suggesting that the manual solicitations applied by MT intervention produce neurophysiological responses able to modulate the pain experience [12,[28][29][30]. These responses can occur at three levels: 1) peripheral, that is, at the tissue level, where the application of MT induces a modulation of inflammatory response after tissue injury [31,32]; 2) spinal: mechanical solicitations activate somato-autonomic reflexes, which in turn produce indirect neuromuscular responses and trigger intrinsic spinal networks through spino-spinal loops [33]; and 3) supraspinal, the use of manual contact might regulate brain areas like anterior cingulate cortex, amygdala or periaqueductal grey, which are crucial, for example, in pain experience, autonomic responses and hypoalgesia [28,29]. Interestingly, these three levels were considered by King and colleagues as the key elements of the autonomic response of MT [34]. ...
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Background The impact of manual therapy interventions on the autonomic nervous system have been largely assessed, but with heterogeneous findings regarding the direction of these effects. We conducted an overview of systematic reviews to describe if there is a specific autonomic effect elicited by manual therapy interventions, its relation with the type of technique used and the body region where the intervention was applied. Methods We conducted an overview according to a publicly registered protocol. We searched the Cochrane Database of Systematic Reviews, MEDLINE, EPISTEMONIKOS and SCOPUS, from their inception to march 2021. We included systematic reviews for which the primary aim of the intervention was to assess the autonomic effect elicited by a manual therapy intervention in either healthy or symptomatic individuals. Two authors independently applied the selection criteria, assessed risk of bias from the included reviews and extracted data. An established model of generalisation guided the data analysis and interpretation. Results We included 12 reviews (5 rated as low risk of bias according the ROBIS tool). The findings showed that manual therapies may have an effect on both sympathetic and parasympathetic systems. However, the results from included reviews were inconsistent due to differences in their methodological rigour and how the effects were measured. The reviews with a lower risk of bias could not discriminate the effects depending on the body region to which the technique was applied. Conclusion The magnitude of the specific autonomic effect elicited by manual therapies and its clinical relevance is uncertain. We point out some specific recommendations in order to improve the quality and relevance of future research in this field.
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Objective The purpose of this study was to assess the feasibility of the procedures’ routine, the recruiting rate, the presence of any significant detrimental impact on the players’ training routine, and the sham efficacy in achieving blinding. Methods A parallel randomized controlled clinical trial was performed with 20 elite soccer players who were randomly assigned to 1 of 2 groups: spinal manipulative therapy (SMT) and sham SMT. All players were from the same team, were injury free, and were naive to SMT. Measured outcome tests (30-m sprint run with a 10-m split and change of direction [COD] test) were performed at the same time by all participants immediately before and after interventions. Photocell devices were used for data acquisition. Results Twenty participants were analyzed (10 in each group). There were no changes to the sprint (10 m and 30 m) and COD test results immediately after either of the interventions. All participants in both groups (SMT and sham SMT) answered “yes” to a question after the intervention asking if they were treated by SMT. No adverse effects or training routine impairment were reported. Conclusion This pilot study protocol showed it was an appropriate design for a confirmatory clinical trial. The study had minimal effect on the team training routine, and the recruitment rate was excellent. The proposed sham SMT strategy was successful in blinding the players. In this sample, SMT did not have any immediate effect on the performance of these elite soccer players, as measured by 10- and 30-m sprint times and COD sprint times.
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