Figure 8.

Putative model for elucidating the relationship between TGF-β1 and bone cancer pain. With the development of bone cancer, cancer cells secrete factors that result in osteoclastogenesis. TGF-β1 is released by osteoclast bone resorption and binds with high affinity and selectivity to the membrane-spanning TGFβRII on nociceptors. Activated TGFβRII recruits and activates TGFβRI, which enables the subsequent phosphorylation of downstream intracellular signals, such as PKC and TAK1-p38, leading to the sensitization of TRPV1.