TLR4 and Arthritis: Interestingly, peripheral HMGB1 mediates collagen-antibody-induced arthritis-mediated nociceptor hypersensitivity in male, but not female, mice, and intra-articular injection of HMGB1 causes resident macrophage-dependent mechanical hypersensitivity via activation of TLR4 only in male mice, suggesting sex differences in the HMGB1/TLR4 axis [51].