Effect of Seated Cervical Spinal Manipulation on Autonomic Nervous System Activity as Measured by Heart Rate Variability and Plasma Norepinephrine Levels: A randomized Pre- and Poststudy.

OBJECTIVE: The objective of this study was to determine whether seated cervical manipulation produced changes in autonomic nervous system activity, as measured by heart rate variability and plasma norepinephrine levels. METHODS: Ninety-five healthy young adults (ages 20-48 years) were recruited into a single-blinded physiological study, with 47 randomized to a seated cervical manipulation and 44 randomized to a sham procedure. Heart rate variability in the frequency domain, and plasma norepinephrine levels were measured prior to, immediately following, and 5 minutes following the intervention. RESULTS: Electrocardiograms were obtained from 39 subjects in the sham group and 43 subjects in the manipulation group. No statistically significant changes were found in measures of heart rate variability in the frequency domain in either the manipulation or sham groups. Blood samples were obtained from 22 subjects in the sham group and 27 subjects in the manipulation group. Plasma norepinephrine levels, as measured by spectrophotometry, declined in both groups from pre- to immediately postintervention, and they remained at decreased levels 5 minutes after the interventions. There were no statistically significant differences between groups in pre- or postintervention norepinephrine levels. CONCLUSIONS: Measures of heart rate variability and plasma norepinephrine levels did not show that seated cervical manipulation produced short-term changes in autonomic nervous system activity compared to a sham procedure in healthy young adults.

Assessment of Studies Evaluating Spinal Manipulative Therapy and Infectious Disease and Immune System Outcomes: A Systematic Review.

Importance: Claims that spinal manipulative therapy (SMT) can improve immune function have increased substantially during the COVID-19 pandemic and may have contributed to the rapid spread of both accurate and inaccurate information (referred to as an infodemic by the World Health Organization). Objective: To identify, appraise, and synthesize the scientific literature on the efficacy and effectiveness of SMT in preventing the development of infectious disease or improving disease-specific outcomes in patients with infectious disease and to examine the association between SMT and selected immunological, endocrine, and other physiological biomarkers. Evidence Review: A literature search of MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, the Index to Chiropractic Literature, the Cochrane Central Register of Controlled Trials, and Embase was conducted from inception to April 15, 2020. Randomized clinical trials and cohort studies were included. Eligible studies were critically appraised, and evidence with high and acceptable quality was synthesized using the Synthesis Without Meta-Analysis guideline. Findings: A total of 2593 records were retrieved; after exclusions, 50 full-text articles were screened, and 16 articles reporting the findings of 13 studies comprising 795 participants were critically appraised. The literature search found no clinical studies that investigated the efficacy or effectiveness of SMT in preventing the development of infectious disease or improving disease-specific outcomes among patients with infectious disease. Eight articles reporting the results of 6 high- and acceptable-quality RCTs comprising 529 participants investigated the effect of SMT on biomarkers. Spinal manipulative therapy was not associated with changes in lymphocyte levels or physiological markers among patients with low back pain or participants who were asymptomatic compared with sham manipulation, a lecture series, and venipuncture control groups. Spinal manipulative therapy was associated with short-term changes in selected immunological biomarkers among asymptomatic participants compared with sham manipulation, a lecture series, and venipuncture control groups. Conclusions and Relevance: In this systematic review of 13 studies, no clinical evidence was found to support or refute claims that SMT was efficacious or effective in changing immune system outcomes. Although there were limited preliminary data from basic scientific studies suggesting that SMT may be associated with short-term changes in immunological and endocrine biomarkers, the clinical relevance of these findings is unknown. Given the lack of evidence that SMT is associated with the prevention of infectious diseases or improvements in immune function, further studies should be completed before claims of efficacy or effectiveness are made.

Effect of Interactive Neurostimulation Therapy on Inflammatory Response in Patients With Chronic and Recurrent Mechanical Neck Pain.

OBJECTIVE: The purpose of this study is to evaluate the effect of treatment with a novel noninvasive interactive neurostimulation device (InterX5000) on the production of inflammatory biomarkers in chronic and recurrent mechanical neck pain (NP) syndrome. METHODS: This study represents pilot biological data from a randomized controlled clinical trial. Twenty-five NP patients and 14 asymptomatic subjects included for baseline comparison only completed the study. The patients received 6 InterX5000 or placebo treatments within 2 weeks, and pretreatment and post-treatment blood samples were collected for in vitro determination of biomarker production. Whole blood cell cultures were activated by lipopolysaccharide or by the combination of lipopolysaccharide and phytohemagglutinin for 24 to 48 hours. The levels of tumor necrosis factor α (TNFα) and its soluble type II receptor (sTNFR II), interleukin (IL) 1, IL-1 receptor antagonist (IL-1RA), IL-6, IL-10, and monocyte chemotactic protein (CCL2/MCP-1) were determined by specific immunoassays. RESULTS: Compared with asymptomatic subjects, baseline production levels of all proinflammatory mediators (TNFα, IL-1ß, IL-6, and CCL2/MCP-1) were significantly augmented or trended higher (P = .000-.008) in patients with NP. Of the anti-inflammatory markers, only IL-1RA was significantly elevated (P = .004). The increase in IL-10 and tumor necrosis factor receptor II levels did not reach statistical significance. Neither InterX5000 nor placebo therapy had any significant effect on the production of the inflammatory mediators over the study period. CONCLUSION: This investigation determined that inflammatory cytokine pathways are activated in NP patients but found no evidence that a short course of InterX5000 treatment normalized the production of inflammatory biomarkers.

Elevated production of inflammatory mediators including nociceptive chemokines in patients with neck pain: a cross-sectional evaluation.

OBJECTIVE: This study investigated whether the production of inflammatory mediators and chemotactic cytokines (chemokines) is altered in patients with chronic and recurrent neck pain (NP). METHODS: Cross-sectional data evaluating blood and serum samples were obtained from 27 NP patients and 13 asymptomatic (control) subjects recruited from a chiropractic outpatient clinic. Cell cultures were activated by lipopolysaccharide (LPS) and phytoheamagglutinin for 24 to 48 hours. The levels of tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1, also known as CCL2 (CCL2/MCP-1), and macrophage inflammatory protein 1α or CCL3 (CCL3/MIP-1α) were determined by specific immunoassays. Serum levels of nitric oxide metabolites were evaluated simultaneously, in vanadium III-reduced samples, by Griess reaction. RESULTS: Low levels of constitutive (spontaneous) TNF-α production were present in 7 of the 27 cultures from patients with NP. Both LPS-induced TNF-α production and inducer (LPS/phytoheamagglutin)-stimulated production of CCL2 were significantly elevated (P = .00) in patients compared with controls. In patients, the constitutive synthesis of CCL3 occurred significantly more frequently (P = .00) and ranged from 30 to more than 2000 pg/mL. Finally, serum levels of nitric oxide were significantly elevated (P = .00) in NP patients. CONCLUSIONS: Production of inflammatory mediators was consistently elevated in NP patients in this study, both in vitro and in vivo, and activation of inflammatory pathways was accompanied by up-regulation of CC chemokine synthesis. This suggests that, in NP patients, CC chemokines may be involved in regulation of local inflammatory response through recruitment of immune cells to the inflamed tissue and exert pronociceptive effects.

Spinal manipulative therapy reduces inflammatory cytokines but not substance P production in normal subjects.

OBJECTIVE: 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). METHODS: 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. RESULTS: Over the study period, a significant proportion (P