Bone cancer pain not only induces bone destruction and unbearable mechanical allodynia, but also up-regulates the spinal expression of ER stress markers, including glucose-regulated protein 78 (GRP78), activating transcription factor-6 (ATF6), phosphorylated protein kinase RNA-like endoplasmic reticulum kinase (p-PERK), phosphorylated inositol-requiring enzyme-1 (p-IRE1) and cleaved caspase-3. This evidence concerns the gene ERN1 and bone cancer.