Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain.
In this study we investigated the role of endothelin-1 (ET-1) and its peripheral receptor (ET-A) in carcinoma-induced pain in a mouse cancer pain model. Tumors were induced in the hind paw of female mice by local injection of cells derived from a human oral squamous cell carcinoma (SCC). Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at four days after SCC inoculation and lasted to 28 days, the last day of measurement. Intra-tumor expression of both ET-1 mRNA and ET-1 protein were significantly upregulated compared to normal tissue, and local administration of the ET-A receptor selective antagonist, BQ-123 (100 microM) significantly elevated withdrawal thresholds, indicating the induction of an antinociceptive effect. These findings support the suggestion that ET-1 and ET-A receptors contribute to the severity of carcinoma-induced soft tissue cancer pain.
Schmidt
Brian L
BL
Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA 94143-0440, USA. Brian.Schmidt@ucsf.edu
Pickering
Victoria
V
Liu
Stanley
S
Quang
Phuong
P
Dolan
John
J
Connelly
S Thaddeus
ST
Jordan
Richard C K
RC
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D045744:Cell Line, Tumor; D003470:Culture Media; D065130:Endothelin A Receptor Antagonists; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009020:Morphine / Q000494:pharmacology; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000188:drug therapy* / Q000209:etiology* / Q000523:psychology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000701:Analgesics, Opioid; D003470:Culture Media; D065130:Endothelin A Receptor Antagonists; D010456:Peptides, Cyclic; D012333:RNA, Messenger; D009020:Morphine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)