gms | German Medical Science

Background: Destruction of cartilage and bone is a major feature in the advanced stage of rheumatoid arthritis (RA), and joint pain is an important clinical problem of RA patients. However, it is unclear whether pain is mainly due to inflammatory processes or whether bone erosion in the late, destructive stage of arthritis significantly contributes to pain. This study aimed to determine the contribution of bone destruction to joint pain in a murine model of chronic RA.

Methods: Glucose-6-phosphate isomerase (G6PI)-induced arthritis was induced in DBA/1 mice. In one group of mice regulatory T-cells (Treg) were depleted by anti-CD25 antibodies. In a further step osteoclast activity in one group of mice was inhibited by continuous treatment with zoledronic acid (ZA). Throughout the course of G6PI-arthritis signs of inflammation (swelling, redness), the gait score, and pain-related behavior were monitored at the paws, and finally bone destruction was determined by µ-CT.

Results: G6PI-induced arthritis caused disturbances of gait and persistent mechanical hyperalgesia at the paws outlasting inflammation, and reversible thermal hyperalgesia at the paws. Treg-depletion led to a non-remitting destructive G6PI-arthritis with severe clinical signs of inflammation and bone destruction, stronger gait disturbances and persistent thermal hyperalgesia while mechanical hyperalgesia was similar as in G6PI arthritis without Treg depletion. In mice with Treg-depletion, ZA-treatment did not affect inflammation but significantly reduced bone destruction, gait abnormalities and thermal hyperalgesia whereas mechanical hyperalgesia at the paws was not reduced. Overall, bone destruction and pain in late destructive arthritis were not correlated.

Conclusion: G6PI-induced arthritis is associated with pain which outlasts the inflammatory phase. Treg depletion intensifies and prolongs inflammation and some pain parameters but does not further increase local mechanical hyperalgesia. These data suggest that persistent pain is triggered by inflammatory mechanisms in the early phase of arthritis. The minor effect of ZA-treatment on pain suggests that even in the chronic stage inflammatory processes rather than bone destruction determine the severity of pain.