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


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.


RESULTS
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.


CONCLUSIONS
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.
Lozano-Ondoua
Alysia N
AN
Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724, United States.
Wright
Courtney
C
Vardanyan
Anna
A
King
Tamara
T
Largent-Milnes
Tally M
TM
Nelson
Mark
M
Jimenez-Andrade
Juan Miguel
JM
Mantyh
Patrick W
PW
Vanderah
Todd W
TW
D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001859:Bone Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging; D001862:Bone Resorption / Q000188:drug therapy* / Q000209:etiology; D002186:Cannabinoids / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D005266:Femoral Neoplasms / Q000150:complications / Q000000981:diagnostic imaging; D005269:Femur / Q000473:pathology; D050723:Fractures, Bone / Q000209:etiology / Q000517:prevention & control; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D011859:Radiography; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists; D012509:Sarcoma / Q000150:complications
C439263:AM 1241; D000700:Analgesics; D002186:Cannabinoids; D043885:Receptor, Cannabinoid, CB2