Zhang et al. [43] found that up-regulation of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) in periaqueductal gray matter of cancer rats amplified PI3K-mTOR signal in this brain region and changed the descending pathway of pain transmission; thus, facilitating the occurrence of bone cancer-induced pain. The gene discussed is IL1B; the disease is bone neoplasm.