Background/aim: Bone cancer pain (BCP) causes troubles and burdens to patients globally. Increasing evidence proved that neuromedin U receptor 2 (NMUR2) was involved in pains. Our study was performed to investigate the role of NMUR2 on BCP and the underlying mechanism. Methods: The rats were raised and BCP rat model was established by injection with Walker 256 cells. The RNA and protein expression levels of NMUR2 in rat neurons-dorsal spinal cord cells, RNdsc cells were detected by qRT-PCR and western blot. The administration with NMUR2 was via intrathecal injection with siRNA to silence NMUR2. The tolerance of rat to pain was measured by mechanical allodynia test and presented by paw withdrawal threshold (PWT) value. The effects on protein kinase C (PKC)/extracellular regulated protein kinases (ERK) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signal pathways were examined by western blot. Results: The expression of NMUR2 in both mRNA and protein levels was upregulated in BCP rat model. In addition, siRNA injection significantly decreased the expression of NMUR2 on the 3rd, 7th and 14th day. BCP group revealed lower PWT value compared with control while NMUR2 silence increased the PWT value compared with negative control. The phosphorylation of PKC, ERK, PI3K and AKT was increased in BCP model while was decreased by si-NMUR2. PKC/ERK and PI3K/AKT inhibitor administration increased the PWT value compared with BCP group. Conclusion: si-NMUR2 alleviates BCP via inactivation of PKC/ERK and PI3K/AKT signal pathways. (C) 2019 Published by Elsevier Inc.