Associations of Cytokine Concentrations With Key Osteopathic Lesions and Clinical Outcomes in Patients With Nonspecific Chronic Low Back Pain: Results From the OSTEOPATHIC Trial.

The Osteopathic Research Center, University of North Texas Health Science Center Texas College of Osteopathic Medicine, 3500 Camp Bowie Blvd, Fort Worth, TX 76107-2644. .
The Journal of the American Osteopathic Association 09/2012; 112(9):596-605.
Source: PubMed


Little is known about the role that cytokines play in osteopathic manual treatment (OMT) of patients with chronic low back pain (LBP).
To measure the baseline concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in patients with chronic LBP; the correlations of these cytokine concentrations with clinical measures, including the number of key osteopathic lesions; the changes in cytokine concentrations with OMT; and the association of such changes with clinical outcomes. Design: Substudy nested within a randomized controlled trial of OMT for nonspecific chronic LBP.
University-based study in Dallas-Fort Worth, Texas.
Seventy adult research patients with nonspecific chronic LBP.
A 10-cm visual analog scale, the Roland-Morris Disability Questionnaire, and the Medical Outcomes Study Short Form-36 Health Survey were used to measure LBP severity, back-specific functioning, and general health, respectively.
At baseline, IL-1β (ρ=0.33; P=.005) and IL-6 (ρ=0.32; P=.006) were each correlated with the number of key osteopathic lesions; however, only IL-6 was correlated with LBP severity (ρ=0.28; P=.02). There was a significantly greater reduction of TNF-α concentration after 12 weeks in patients who received OMT compared with patients who received sham OMT (Mann-Whitney U=251.5; P=.03). Significant associations were found between OMT and a reduced TNF-α concentration response at week 12 among patients who achieved moderate (response ratio, 2.13; 95% confidence interval [CI], 1.11-4.06; P=.006) and substantial (response ratio, 2.13; 95% CI, 1.07-4.25; P=.01) LBP improvements, and improvement in back-specific functioning (response ratio, 1.68; 95% CI, 1.04-2.71; P=.03).
This study found associations between IL-1β and IL-6 concentrations and the number of key osteopathic lesions and between IL-6 and LBP severity at baseline. However, only TNF-α concentration changed significantly after 12 weeks in response to OMT. These discordant findings indicate that additional research is needed to elucidate the underlying mechanisms of action of OMT in patients with nonspecific chronic LBP.

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Available from: Cathleen M Kearns, Jul 13, 2015
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    • "It is interesting to review potential mechanisms by which OMT may exert its treatment effects in light of our subgroup findings. Previous analyses of OSTEOPATHIC Trial data have found reductions in serum tumor necrosis factor (TNF)-a concentration (Licciardone et al., 2012) and remission of psoas syndrome (Licciardone et al., 2014) to be associated with clinical response to OMT. Cytokines facilitate pain via a pathway that leads to release of neurotransmitters or neuromodulators that activate spinal cord glia and enhance pain (Watkins and Maier, 2005). "
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    ABSTRACT: Clinical response and relapse following a regimen of osteopathic manual treatment (OMT) were assessed in patients with chronic low back pain (LBP) within the OSTEOPATHIC Trial, a randomized, double-blind, sham-controlled study. Initial clinical response and subsequent stability of response, including final response and relapse status at week 12, were determined in 186 patients with high baseline pain severity (≥50 mm on a 100-mm visual analogue scale). Substantial improvement in LBP, defined as 50% or greater pain reduction relative to baseline, was used to assess clinical response at weeks 1, 2, 4, 6, 8, and 12. Sixty-two (65%) patients in the OMT group attained an initial clinical response vs. 41 (45%) patients in the sham OMT group (risk ratio [RR], 1.45; 95% confidence interval [CI], 1.11-1.90). The median time to initial clinical response to OMT in these patients was 4 weeks. Among patients with an initial clinical response prior to week 12, 13 (24%) patients in the OMT group vs. 18 (51%) patients in the sham OMT group relapsed (RR, 0.47; 95% CI, 0.26-0.83). Overall, 49 (52%) patients in the OMT group attained or maintained a clinical response at week 12 vs. 23 (25%) patients in the sham OMT group (RR, 2.04; 95% CI, 1.36-3.05). The large effect size for short-term efficacy of OMT was driven by stable responders who did not relapse.
    Preview · Article · Dec 2014 · Manual Therapy
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    • "Although no identification of the particular mechanism responsible for this effect has yet been determined, this data clearly highlights the capability of OMT to enhance protection against infection. Further, two recent research studies by Licciardone et al. on human patients suffering chronic low back pain showed that repeated OMT treatment was able to modify the levels of TNFα in circulation [26], [27]. Finally, a randomized, controlled clinical trial comparing a standardized lymphatic pump protocol with a light-touch protocol determined that OMT can induce a rapid and significant decrease in the platelet levels in elder patients [28]. "
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    ABSTRACT: It has been claimed that osteopathic manipulative treatment (OMT) is able to enhance the immune response of individuals. In particular, it has been reported that OMT has the capability to increase antibody titers, enhance the efficacy of vaccination, and upregulate the numbers of circulating leukocytes. Recently, it has been shown in human patients suffering chronic low back pain, that OMT is able to modify the levels of cytokines such as IL-6 and TNF-α in blood upon repeated treatment. Further, experimental animal models show that lymphatic pump techniques can induce a transient increase of cytokines in the lymphatic circulation. Taking into account all these data, we decided to investigate in healthy individuals the capacity of OMT to induce a rapid modification of the levels of cytokines and leukocytes in circulation. Human volunteers were subjected to a mixture of lymphatic and thoracic OMT, and shortly after the levels of several cytokines were evaluated by protein array technology and ELISA multiplex analysis, while the profile and activation status of circulating leukocytes was extensively evaluated by multicolor flow cytometry. In addition, the levels of nitric oxide and C-reactive protein (CRP) in plasma were determined. In this study, our results show that OMT was not able to induce a rapid modification in the levels of plasma nitrites or CRP or in the proportion or activation status of central memory, effector memory or naïve CD4 and CD8 T cells. A significant decrease in the proportion of a subpopulation of blood dendritic cells was detected in OMT patients. Significant differences were also detected in the levels of immune molecules such as IL-8, MCP-1, MIP-1α and most notably, G-CSF. Thus, OMT is able to induce a rapid change in the immunological profile of particular circulating cytokines and leukocytes.
    Full-text · Article · Mar 2014 · PLoS ONE
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    ABSTRACT: Chronic inflammatory diseases (CID) are globally highly prevalent and characterized by severe pathological medical conditions. Several trials were conducted aiming at measuring the effects of manipulative therapies on patients affected by CID. The purpose of this review was to explore the extent to which osteopathic manipulative treatment (OMT) can be benefi-cial in medical conditions also classified as CID. This review included any type of experimental study which enrolled sub-jects with CID comparing OMT with any type of control procedure. The search was conducted on eight databases in January 2014 using a pragmatic literature search approach. Two independent re-viewers conducted study selection and data extraction for each study. The risk of bias was evaluated according to the Cochrane methods. Heterogeneity was assessed and meta-analysis performed where possible. 10 studies met the inclusion criteria for this review enrolling 386 subjects. The search identified six RCTs, one laboratory study, one cross-over pilot studies, one observation-al study and one case control pilot study. Results suggest a potential effect of osteopathic medicine on patients with medical pathologies associated with CID (in particular Chronic Obstructive Pul-monary Disease (COPD), Irritable Bowel Syndrome, Asthma and Peripheral Arterial Disease) com-pared to no treatment or sham therapy although data remain elusive. Moreover one study showed possible effects on arthritis rat model. Meta-analysis was performed for COPD studies only show-ing no effect of any type of OMT applied versus control. No major side effects were reported by those receiving OMT. The present systematic review showed inconsistent data on the effect of OMT in the treatment of medical conditions potentially associated with CID, however the OMT appears to be a safe approach. Further more robust trials are needed to determine the direction and magnitude of the effect of OMT and to generalize favorable results.
    Full-text · Article · Mar 2015 · PLoS ONE
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