Anti-inflammatory Actions of Osteopathic Manipulative Treatment

Anti-inflammatory Actions of OMT - Role of the Cholinergic Anti-inflammatory Pathway and Translocation of Immune Cells From Reticular Organs to the Systemic Circulation

This study evaluates the hypothesis that osteopathic manipulative treatment (OMT) and non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) elicit anti-inflammatory actions through activation of the parasympathetic nervous system. In a cross-over design, research participants will be subjected to various combinations of OMT, taVNS, or sham interventions during four study sessions, that are at least one month apart. During each study session research participants will undergo OMT and/or taVNS for 3 consecutive days. Blood pressure and electrocardiogram (ECG) will be recorded on all three study days to assess parasympathetic nervous system function. On the 3rd study day a blood sample will be taken to assess the effects of OMT and/or taVNS on inflammation.

Biological anti-inflammatory drugs, such as TNF-α antagonists, have revolutionized treatment of chronic inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, psoriasis, or other auto-immune disorders and have largely improved prognosis and quality of life of patients affected by these conditions. However, the high cost of these agents is prohibitive for a large number of patients and some patients are not eligible to such treatments because of co-morbidities that constitute contraindications. Thus, there is a need for cost-effective alternative treatment strategies. Activation of the cholinergic anti-inflammatory pathway, which operates through the parasympathetic nervous system, may constitute an alternative approach to treat chronic inflammatory diseases. This pathway has been demonstrated to shift the function of immune cells in reticular organs, such as the spleen from a pro-inflammatory to an anti-inflammatory state. Subsequently, these "reprogrammed" cells translocate to the systemic circulation and reach the site of inflammation. Clinical studies and the investigators' preliminary data suggest that non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) can augment parasympathetic tone and potentially activate the cholinergic anti-inflammatory pathway. Another way of potentially activating this pathway is through osteopathic manipulative treatment (OMT) because some OMT techniques have been demonstrated to increase parasympathetic activity. However, it is not known if such OMT techniques also activate the cholinergic anti-inflammatory pathway. Furthermore, it is not known if osteopathic lymphatic pump techniques augment these anti-inflammatory responses by facilitating translocation of "reprogrammed" immune cells from reticular organs to the systemic circulation. The investigators' long-term goal is to contribute to the development of cost-effective OMT approaches to treat chronic inflammatory diseases. The central hypothesis is that successive applications of different OMT techniques or the combination of taVNS with specific OMT techniques first activate and then augment the cholinergic anti-inflammatory pathway through stimulating parasympathetic tone and facilitating translocation of immune cells. Parasympathetic nervous system function will be assessed by heart rate variability analysis and other cardiovascular parameters that are under the influence of the parasympathetic nervous system. Immune function will be assessed by measuring plasma concentrations of inflammatory mediators (cytokines) and by in vitro cell culture experiments of immune cells. At the completion of these studies, the investigators anticipate to demonstrate that OMT techniques that activate the parasympathetic nervous system and taVNS elicit anti-inflammatory effects. Second, the investigators also anticipate to demonstrate that subsequently applied osteopathic lymphatic pump techniques augment the anti-inflammatory actions of OMT and taVNS by facilitating translocation of "reprogrammed" immune cells from the spleen to the systemic circulation. These outcomes are expected to have important positive impact, because they will potentially lay a mechanistic foundation for future clinical studies applying such combinations of taVNS and OMT techniques to chronic inflammatory diseases, including inflammatory bowel diseases, rheumatoid arthritis, psoriasis, or other auto-immune disorders.

Inclusion Criteria:

• Age of 18 year or above.

Exclusion Criteria:

• Age under 18 years
• Pregnancy
• Any findings on the osteopathic screening/evaluation that would hinder the effectiveness - of the occipito-atlantal decompression or splenic lymphatic pump technique
• Any medication that interferes with the autonomic nervous system function or the immune system (e.g., beta-blockers, steroids, TNF-α inhibitors)
• Any medical condition that affects the autonomic nervous system or the immune system (e.g., splenomegaly, Epstein-Barr infection within the last 6 months, autonomic neuropathy, pure autonomic failure, rheumatic or autoimmune diseases, acquired autoimmune deficiency syndrome)
• Any chronic diseases, such as diabetes and hypertension
• Current drug or alcohol abuse.