Fig. 1

The potential role of S100 proteins in the pathophysiology of fibromyalgia. S100A8, S100A9, S100A8/A9, S10012, and S100B bind to RAGE, while S100A8, S100A8, and S100A8/A9 dimer bind to toll-like receptor (TLR4). Both RAGE and TLR4 signal through JNK, ERK, and p38 to activate the transcription factors AP-1 (Activating Protein-1) and NF-κB (nuclear factor kappa B), which in turn induce the release of proinflammatory cytokines. These proinflammatory cytokines, coupled with the presence of hyperalgesia and central sensitization, may contribute to inflammation, fatigue and chronic pain