Previous studies in the bone cancer pain model and CCI-induced neuropathic pain model demonstrated that EphB1 receptor antagonist relieved hyperalgesia and allodynia by downregulating phosphorylation of NR1, NR2B, Src, ERK, MK2, and CREB or reducing activation of ERK5/CREB in the spinal cord [18, 29]. This evidence concerns the gene CREB1 and bone neoplasm.