In addition, IL-1β, IL-6, and TNF-α were elevated in the periaqueductal gray of bone cancer rats, and expression of their respective receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor (TNFR) subtype TNFR1) was upregulated.
Bone cancer resulted in the activation of astrocytes and microglia in the SDH through the upregulation of mitogen-activated protein kinase (MAPK) pathways, which was accompanied by an over-expression of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6.
The control mice were intrathecally injected with tumor necrosis factor-α (TNF-α) and lipopolysaccharide, the bone cancer pain mice were intrathecally injected with the endoplasmic reticulum stress inhibitors 4-PBA and GSK2606414.