Objectives Musculoskeletal pain and fatigue are common features in systemic lupus erythematosus (SLE). The cholinergic anti-inflammatory pathway is a physiological mechanism diminishing inflammation, engaged by stimulating the vagus nerve. We evaluated the effects of non-invasive vagus nerve stimulation in patients with SLE and with musculoskeletal pain.
Methods 18 patients with SLE and with musculoskeletal pain ≥4 on a 10 cm Visual Analogue Scale were randomised (2:1) in this double-blind study to receive transcutaneous auricular vagus nerve stimulation (taVNS) or sham stimulation (SS) for 4 consecutive days. Evaluations at baseline, day 5 and day 12 included patient assessments of pain, disease activity (PtGA) and fatigue. Tender and swollen joint counts and the Physician Global Assessment (PGA) were completed by a physician blinded to the patient’s therapy. Potential biomarkers were evaluated.
Results taVNS and SS were well tolerated. Subjects receiving taVNS had a significant decrease in pain and fatigue compared with SS and were more likely (OR=25, p=0.02) to experience a clinically significant reduction in pain. PtGA, joint counts and PGA also improved. Pain reduction and improvement of fatigue correlated with the cumulative current received. In general, responses were maintained through day 12. Plasma levels of substance P were significantly reduced at day 5 compared with baseline following taVNS but other neuropeptides, serum and whole blood-stimulated inflammatory mediators, and kynurenine metabolites showed no significant change at days 5 or 12 compared with baseline.
Conclusion taVNS resulted in significantly reduced pain, fatigue and joint scores in SLE. Additional studies evaluating this intervention and its mechanisms are warranted.
- lupus erythematosus
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Handling editor Josef S Smolen
Presented at This work was presented as a poster presentation at the 2018 American College of Rheumatology/Association of Rheumatology Professionals Annual Meeting: Aranow C, Lesser M, Mackay M et al. Engaging the Cholinergic Anti-Inflammatory Pathway By Stimulating the Vagus Nerve Reduces Pain and Fatigue in Patients with SLE [abstract]. Arthritis Rheumatol. 2018;70 (suppl 10).
Contributors CA, MM, CB, KJT and BD: study design. CA, YA-F, EA, SC, TPZ, TD-C: data acquisition. CA, YA-F, ML, MM, EA, SC, TDZ, TD-C, CB, KJT and BD: data analysis. CA, YA-F, ML, MM, EA, SC, TDZ, TD-C, CB, KJT and BD: interpretation of findings. CA, YA-F, ML, MM, EA, SC, TDZ, TD-C, CB, KJT and BD: preparation of manuscript. All authors approved the final manuscript.
Funding This is an investigator initiated study supported by a grant from the John and Marcia Goldman Foundation.
Competing interests KJT reports a financial relationship with Set Point Medical and My String; Prof. CB and Assistant Professors TPZ and Datta-Chaudhuri have a provisional patent application: "Auricular stimulation device, system and methods of use".
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. All data relevant to the study are included in the article or uploaded as supplementary information.
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