BACKGROUND: In rheumatoid arthritis (RA) synovitis, activation of synoviocytes and infiltration of adaptive immune cells leads to synovial hyperplasia and joint swelling. Under the elevated extra-neural pressure, free nerve endings release neuropeptides, calcitonin gene-related peptide, and substance P, thus promoting neurogenic inflammation. OBJECTIVE: This study aimed to assess the effect of therapeutic neural mobilization (NM) exercises targeting the nervous system on disease impact in RA patients. METHODS: A total of 21 RA patients were randomized into NM (n = 11) and control (n = 10) groups. NM group patients performed NM exercises targeting the median, musculocutaneous, femoral, and saphenous nerve, as well as the entire nervous system twice daily for 4 to 8 weeks. Control RA patients performed gentle joint mobilization exercises targeting the same joints. Primary outcome was the change in pre-/post-treatment score in the validated Rheumatoid Arthritis Impact of Disease (RAID). Secondary outcome was erythrocyte sedimentation rate (ESR). RESULTS: There were no significant differences between the groups at baseline. No adverse events were observed and compliance was over 90%. Post-treatment, favorable changes were observed in the NM group RAID score -5.1 versus -0.8; weighted RAID score -0.79 versus -0.15. ESR was reduced in the NM group, albeit non-significantly. Regarding the RAID score domains, the NM group demonstrated significant improvements in pain and coping. CONCLUSION: The current data indicate a beneficial effect of NM exercises on pain and self-efficacy in our RA patients. Larger clinical studies are warranted to determine the clinical effectiveness of NM as a treatment for pain for RA patients and simultaneously address immune and neuropeptide modulation through NM.

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