K/BxN serum transfer arthritis as a model of inflammatory joint pain

Abstract

In this chapter, we describe the usage of this rheumatoid arthritis model to investigate pain-like behavior in mice, including the assessment of clinical changes and the time-dependent changes in nociceptive behavior during disease progresses.

Fig. 1

Clinical and pathological signs following induction of K/BxN serum transfer arthritis. Images of footpads (a, b) and joints (c) from control serum-treated mice are readily differentiable from images of footpads (d, e) and joints (f) from K/BxN serum transfer arthritis. The swelling in arthritic mice is sufficient to make the ankle wider than the midfoot region and to produce distinct redness and swelling of individual knuckles. Histopathology of the knee joints from arthritic and control mice on days 6 and 28 was sectioned and stained with hematoxylin and eosin. There is a prominent inflammatory infiltration on day 6 in the mice that received K/BxN sera (i; white arrow) and residual bony erosions on day 28 (j; black arrow), which are absent in control sections (g, h). Representative images are shown (original ×50 magnification). Graphs display (k) arthritis clinical scores assessed for 28 days, demonstrating an increase in clinical signs of arthritis day 1–12 and (I) ankle thickness measured with calipers showing a significant ankle swelling in arthritic animals day 3–9. Each time point represents mean±SEM (n=9 mice/group), ^*p<0.05, ^**p<0.01, and ^***p<0.001 by Bonferroni post-test. Panels g–l have been reproduced from ref. with permission from the International Association for the Study of Pain (IASP).

Fig. 2

Characterization of mechanical hypersensitivity in mice subjected to K/BxN serum transfer arthritis. Graph displays 50% tactile thresholds (g) showing tactile allodynia day 2–28 (excluding day 12). Each time point represents mean±SEM (n=9 mice/group), *p<0.05, **p<0.01, and ***p<0.001 by Bonferroni post-test. Figure 2 has been reproduced from ref. with permission from the International Association for the Study of Pain (IASP).

Fig. 3

Characterization of thermal sensitivity induced by K/BxN serum transfer arthritis. Graph displays thermal thresholds (s) demonstrating that arthritic animals display thermal hypoalgesia day 3–6, with no other changes from baseline. Each time point represents mean±SEM (n=9 mice/group), *p< 0.05, **p< 0.01, and ***p< 0.001 by Bonferroni post-test. Figure 3 has been reproduced from ref. with permission from the International Association for the Study of Pain (IASP).

Fig. 4

Activity monitoring in control mice and mice subjected to K/BxN serum transfer arthritis. Graph displays activity counts registered during the 12-h dark cycle. Arthritic mice display significantly reduced activity on days 3,4,5,7, and 8 following K/BxN serum transfer. Each time point represents mean±SEM (n=5–10 mice/group), *p<0.05, **p<0.01, and ***p<0.001 by Bonferroni post-test.