Peripheral endothelin A receptor antagonism attenuates carcinoma-induced pain

Brian L. Schmidt, Victoria Pickering, Stanley Liu, Phuong Quang, John Dolan, S. Thaddeus Connelly, Richard C.K. Jordan

Research output: Contribution to journalArticlepeer-review


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 μM) 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.

Original languageEnglish (US)
Pages (from-to)406-414
Number of pages9
JournalEuropean Journal of Pain
Issue number4
StatePublished - May 2007


  • Cancer pain
  • Endothelin
  • Endothelin A receptor
  • Mouse model
  • Oral cancer

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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