Peripheral cannabinoids attenuate carcinoma-induced nociception in mice.
We investigated the cannabinoid receptor (CBr) agonists Win55,212-2 (non-selective) and AM1241 (CBr2 selective) and the peripheral receptor (CBr1) in carcinoma-induced pain using a mouse model. Tumors were induced in the hind paw of female mice by local injection of a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at 4 days after SCC inoculation and lasted to 18 days. Local administration of Win55,212-2 (10 mg/kg) and AM1241 (10 mg/kg) significantly elevated withdrawal thresholds, indicating an antinociceptive effect. Ipsilateral expression of CBr1 protein in L5 DRG was significantly upregulated compared to ipsilateral L4 DRG and in normal tissue. These findings support the suggestion that cannabinoids are capable of producing antinociception in carcinoma-induced pain.
Guerrero
Andre V
AV
UCSF School of Dentistry, University of California, Sa Francisco, CA 94143-0440, United States.
Quang
Phuong
P
Dekker
Nusi
N
Jordan
Richard C K
RC
Schmidt
Brian L
BL
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines / Q000627:therapeutic use*; D002186:Cannabinoids / Q000627:therapeutic use*; D002277:Carcinoma / Q000150:complications*; D004195:Disease Models, Animal; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009025:Morpholines / Q000627:therapeutic use*; D009281:Naphthalenes / Q000627:therapeutic use*; D018307:Neoplasms, Squamous Cell / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D013116:Spinal Cord / Q000473:pathology; D013997:Time Factors
C439263:AM 1241; D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D043884:Receptor, Cannabinoid, CB1; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone