TY - JOUR
T1 - Intravenous Ibandronate Rapidly Reduces Pain, Neurochemical Indices of Central Sensitization, Tumor Burden, and Skeletal Destruction in a Mouse Model of Bone Cancer
AU - Halvorson, Kyle G.
AU - Sevcik, Molly A.
AU - Ghilardi, Joseph R.
AU - Sullivan, Lucy J.
AU - Koewler, Nathan J.
AU - Bauss, Frieder
AU - Mantyh, Patrick W W.
N1 - Funding Information:
This work was supported by the National Institutes of Health grants NS23970 and NS048021, a Merit Review from the Veterans Administration, and a research grant from Hoffman-La Roche Inc.
PY - 2008/9
Y1 - 2008/9
N2 - Over half of all chronic cancer pain arises from 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 administered either as a single dose (300 μg/kg), at Day 7 post-tumor injection, when tumor-induced bone destruction and pain were first evident, or in three consecutive doses (100 μg/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 for limiting pain and disease progression.
AB - Over half of all chronic cancer pain arises from 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 administered either as a single dose (300 μg/kg), at Day 7 post-tumor injection, when tumor-induced bone destruction and pain were first evident, or in three consecutive doses (100 μg/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 for limiting pain and disease progression.
KW - Tumor bone pain
KW - bisphosphonates
KW - ibandronate
KW - nociception
KW - skeletal malignancies
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U2 - 10.1016/j.jpainsymman.2007.10.005
DO - 10.1016/j.jpainsymman.2007.10.005
M3 - Article
C2 - 18411018
AN - SCOPUS:49749152809
SN - 0885-3924
VL - 36
SP - 289
EP - 303
JO - Journal of Pain and Symptom Management
JF - Journal of Pain and Symptom Management
IS - 3
ER -