SB366791, a TRPV1 antagonist, potentiates analgesic effects of systemic morphine in a murine model of bone cancer pain.
BACKGROUND
Bone cancer pain has a major impact on the quality of life of cancer patients but is difficult to treat. Therefore, development of a novel strategy for bone cancer pain is needed for improvement of the patient quality of life. In this study, we examined the analgesic effects of the combination of a transient receptor potential vanilloid subfamily 1 (TRPV1) antagonist and morphine on pain-related behaviours in a murine model of bone cancer pain.


METHODS
C3H/HeJ mice underwent injection of osteolytic sarcoma cells into the intramedullary space of the femur. The analgesic effects of intraperitoneal morphine and the analgesic effect of a TRPV1 antagonist, SB366791 [N-(3-methoxyphenyl)-4-chlorocinnamide], on bone cancer pain-related behaviours were examined. The analgesic effects of the combination of SB366791 and morphine on bone cancer pain were also examined.


RESULTS
Intraperitoneal morphine significantly reduced the number of spontaneous flinches and improved ambulation only at the highest dose of 10 mg kg(-1) whereas weight-bearing was not improved. Intraperitoneal SB366791 at doses of 0.3 and 1.0 mg kg(-1), but not at a dose of 0.1 mg kg(-1), reduced the number of spontaneous flinches, whereas neither weight-bearing nor ambulation was improved. Addition of a sub-analgesic dose of SB366791 (0.1 mg kg(-1)) to morphine significantly reduced the number of flinches and improved weight-bearing compared with the effects of morphine alone.


CONCLUSIONS
Our findings showed that the combination of morphine and SB366791 has potent analgesic effects on bone cancer pain. The findings of this study may lead to novel strategies for the treatment of bone cancer pain.
Niiyama
Y
Y
Department of Anaesthesiology, Sapporo Medical University School of Medicine, South 1, West 16, Chuo-ku, Sapporo, Hokkaido 060-8543, Japan.
Kawamata
T
T
Yamamoto
J
J
Furuse
S
S
Namiki
A
A
D000284:Administration, Oral; D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000813:Anilides / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001859:Bone Neoplasms / Q000150:complications*; D002934:Cinnamates / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009020:Morphine / Q000627:therapeutic use; D009368:Neoplasm Transplantation; D010147:Pain Measurement / Q000379:methods; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology; D012513:Sarcoma, Experimental / Q000150:complications*; D050916:TRPV Cation Channels / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
D000700:Analgesics; D000701:Analgesics, Opioid; D000813:Anilides; D002934:Cinnamates; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D009020:Morphine