In this study the principal findings are as follows: (1) Intrathecal administration of D1DR/D2DR antagonists or siRNA could significantly alleviate TCI-induced bone cancer pain; (2) D1DR and D2DR form heteromers in spinal neurons that promote bone cancer pain by activating Gq protein and thereby increasing neuronal excitability, leading to the activation of CaMKII and MAPK signaling; (3) l-CDL, a natural compound could attenuate TCI-induced chronic bone cancer pain through inhibiting D1/D2DR heteromers. The gene discussed is CAMK2G; the disease is bone neoplasm.