title: A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss.
abstract: 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.
authors.affiliation: Department of Pharmacology, College of Medicine, The University of Arizona, Tucson, AZ 85724, United States.
authors.forename: Alysia N
authors.initials: AN
authors.lastname: Lozano-Ondoua
authors.forename: Courtney
authors.initials: C
authors.lastname: Wright
authors.forename: Anna
authors.initials: A
authors.lastname: Vardanyan
authors.forename: Tamara
authors.initials: T
authors.lastname: King
authors.forename: Tally M
authors.initials: TM
authors.lastname: Largent-Milnes
authors.forename: Mark
authors.initials: M
authors.lastname: Nelson
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Jimenez-Andrade
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Mantyh
authors.forename: Todd W
authors.initials: TW
authors.lastname: Vanderah
mesh_terms: 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
chemical_list: C439263:AM 1241; D000700:Analgesics; D002186:Cannabinoids; D043885:Receptor, Cannabinoid, CB2