Intravenous ibandronate rapidly reduces pain, neurochemical indices of central sensitization, tumor burden, and skeletal destruction in a mouse model of bone cancer

Over half of all chronic cancer pain arises front metastases to bone and bone cancer pain is one of the most difficult of all persistent pain states to fully control. Currently, bone pain is treated primarily by opioid-based therapies, which are frequently accompanied by significant unwanted side effects. In an effort, to develop nonopioid-based therapies that could rapidly attenuate tumor-induced bone pain, we examined the effect, of intravenous administration of the bisphosphonate, ibandronate, in a mouse model of bone cancer pain. Following injection. and confinement of green fluorescent Protein-transfected murine osteolytic 2472 sarcoma cells into the marrow space of the femur of male C3H/HeJ mice, ibandronate was ad,administered either as a single dose (300 mu g/kg), at Day 7 post-tumor injection, when tumor-induced bone destruction and Pain were first evident, or in three consecutive doses (100 mu g/kg/day) at Days 7, 8, and 9 post-tumor injection. Intravenous ibandronate administered once or in Three consecutive doses reduced ongoing and movement-evoked bone cancer pain-related behaviors, neurochemical markers of central sensitization, tumor burden, and tumor-induced bone destruction. These results support limited, clinical trials that suggest the potential of ibandronate to rapidly attenuate bone pain and illuminate the mechanisms that. may be responsible fir limiting pain and disease progression.