Background: Pain is one of the main symptoms in Rheumatoid Arthritis (RA), and often does not correspond directly to the inflammatory activity of the joints. There is no consensus on the relationship between the systemic inflammatory process and changes in the central nervous system that may influence pain patterns in these patients.

Objectives: Our objective was to evaluate the relationship between neuroinflammatory parameters in the brain and nociceptive parameters in the CIA model.

Methods: CIA was induced in male DBA1/J mice (32) between 8-12 weeks of age, randomized into 4 groups: control group(CO25) and CIA25 days and control group(CO50) and CIA50 days. Clinical score and paw edema were evaluated. Nociception was assessed using Von Frey. After euthanasia, brain were subjected to the immunofluorescence technique with anti-IgM and anti-IgG antibodies, and immunohistochemistry with anti-IL6, and to analyzing the neurodegeneration by Fluoro-Jade C. Data were analyzed by Two-way ANOVA, Kruskal-Wallis and Pearson correlation;p<0.05 was considered significant.

Results: The CIA group had a higher clinical score, paw edema, histological score and nociception compared to the CO group (p<0.0001;p=0.001;p=0.001, respectively). High IgM deposits were observed in the CIA25 group compared to the CO25 group(p=0.01). Regarding IgG, no differences were observed between the CIA and CO groups at the two moments evaluated. IL6 expression was increased in the CIA50 group when compared to CO50(p=0.008). An association was identified between the clinical score and the expression of IL6 in the brain only in the CIA25 group(p=0.08). IL6 expression was also associated with pain threshold at disease time 25(p=0.002) and 50(p=0.022). The quantification of degenerated neurons did not show a statistically significant difference, but there is a tendency for an increase in the number of degenerated neurons in mice in the CIA50 group when compared to the CO50 group.

Conclusion: Clinical, paw edema, histological and nociceptive scores characterized the presence of arthritis in the model. In the acute phase of the disease, high IgM deposits were identified in the brain, while in the established phase only ILi6 expression was increased. An association was observed between IL6 and the clinical score in the initial period of the disease, as well as with the pain threshold in both periods of the disease (25 and 50 days). These results demonstrate the presence of neuroinflammation in this arthritic model.

REFERENCES: [1] Atzeni F, Talotta R, Masala IF, Gerardi MC, Casale R, Sarzi-Puttini P. Central nervous system involvement in rheumatoid arthritis patients and the potential implications of using biological agents. Vol. 32, Best Practice and Research: Clinical Rheumatology. 2018. p. 500–10.

[2] Stüve O, Zettl U. Neuroinflammation of the central and peripheral nervous system: An update. Vol. 175, Clinical and Experimental Immunology. 2014. p. 333–5.

[3] Brooks TA, Hawkins BT, Huber JD, Egleton RD, Davis TP. Chronic inflammatory pain leads to increased blood-brain barrier permeability and tight junction protein alterations. Am J Physiol Heart Circ Physiol. 2005;289:738–43.

[4] Schaible HG. Nociceptive neurons detect cytokines in arthritis. Vol. 16, Arthritis Research and Therapy. 2014. p. 470.

Acknowledgements: CAPES, CNPq, FIPE-HCPA.

Disclosure of Interests: None declared.