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Effects of Lymphatic Pump Treatment and Methotrexate in Arthritis Development and Behavior in Rats with Adjuvant-Induced Arthritis

Journal: Journal of Osteopathic Medicine Date: 2025/12, 125(12):Pages: A638–639. doi: Subito , type of study: animal experiment

Full text    (https://www.degruyterbrill.com/document/doi/10.1515/jom-2025-2000/html)

Keywords:

animal experiment [67]
LPT [27]
lymphatic pump treatment [5]
rats [14]
rheumatoid arthritis [6]

Abstract:

Context: Rheumatoid arthritis is a systemic autoimmune disease characterized by joint inflammation that eventually leads to joint destruction and loss of bone and cartilage. Osteopathic manipulative medicine is a unique treatment approach that aligns with the osteopathic philosophy that the body maintains and self-heals under optimal conditions. Lymphatic pump treatment (LPT) is an osteopathic manipulative technique that serves a therapeutic role in increasing the drainage of inflammatory cells and mediators away from the arthritic joint. Methotrexate (MTX) is a first-line disease-modifying anti-rheumatic drug (DMARD) that is commonly used in rheumatoid arthritis treatment. However, MTX has been known to have increased levels of toxicity at high doses. We are studying whether implementing LPT along with low doses of MTX will significantly improve the efficacy of MTX. Objective: To determine whether Lymphatic Pump Treatment (LPT) impacts Rheumatoid Arthritis disease progression as an independent treatment and as an adjunct to Methotrexate treatment. Methods: A 13-day preventative rat study was performed. MTX was given 3 times to certain groups. LPT was administered daily 3 times a day to certain groups for 9 days. Ankle circumference, articular index scores (AIS), and pain scores were recorded daily as a measurement of inflammation. Spleen and popliteal lymph nodes (PLN) samples were collected. Flow cytometry was performed on cells from PLNs and spleens labeled for CD3, CD4, CD8, CD25, CD45R. ELISAs performed on homogenized ankle lysates were used to analyze CINC-1, CINC-2, TNF-α, IL-1β, and IL-6 levels. H&E staining was performed on ankle sections to evaluate tissue erosion, lining, and inflammation. Results: MTX was shown to delay the development of arthritis. Animals receiving MTX showed significance of index score and ankle circumference by day 13, which indicated the therapeutic effect of MTX. The spleen weight significantly decreased with MTX treatment, but was unchanged with the lymphatic pump treatment (p<0.05). The PLN weight showed variability between animals in different treatment groups with no significant difference in the animals that received LPT. Through flow cytometry, animals that underwent MTX treatment had increased levels of CD3+ and CD4+ in the spleen. There were no significant changes in cell population in the PLNs. For both CINC-1 and CINC-2, there was no statistical significance for the animals that received LPT as an intervention. The animals that received MTX intervention resulted in a statistically significant decrease in CINC-1 and CINC-2. Conclusion: MTX treatment delayed the development of AIA per ankle circumference and AIS. MTX significantly decreased levels of cytokines and chemokines in the AIA model. LPT as an intervention showed no difference in results from the sham model. Based on this study, LPT did not show negative effects as an adjunct treatment for RA. Future studies could use lower concentrations of MTX to determine potential adjunct therapeutic effects of LPT when added to MTX treatment. The MTX may be so effective that it is masking the effects of LPT.


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