A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss.

TitleA cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss.
Publication TypeJournal Article
Year of Publication2010
AuthorsLozano-Ondoua AN, Wright C, Vardanyan A, King T, Largent-Milnes TM, Nelson M, Jimenez-Andrade JMiguel, Mantyh PW, Vanderah TW
JournalLife Sci
Date Published2010 Apr 24
KeywordsAnalgesics, Animals, Bone Neoplasms, Bone Resorption, Cannabinoids, Disease Models, Animal, Femoral Neoplasms, Femur, Fractures, Bone, Male, Mice, Mice, Inbred C3H, Neoplasm Transplantation, Pain, Radiography, Receptor, Cannabinoid, CB2, Sarcoma

AIMS: Cannabinoid CB(2) agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB(2) agonist, does not demonstrate central nervous system side effects seen with CB(1) agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB(2) selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB(2) agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation.

MAIN METHODS: A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur.

KEY FINDINGS: Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures.

SIGNIFICANCE: These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.

Alternate JournalLife Sci.
PubMed ID20176037
PubMed Central IDPMC2871326
Grant ListR01 CA142115 / CA / NCI NIH HHS / United States
R01 CA142115-01A1 / CA / NCI NIH HHS / United States
Faculty Member Reference: 
Tally Largent-Milnes, PhD
Patrick W Mantyh
Todd Vanderah, PhD