Endothelin-1 and metastatic cancer pain

Pain in patients with metastatic cancer contributes to increased suffering in those already burdened by their advancing illness. The causes of this pa in are unknown but likely to involve the action of tumor-associated mediato rs and their receptors. One such mediator, endothelin-1 (ET-1), can induce both pain-like behavior in animals and pain in humans that is endothelin-A (ETA) receptor-dependent, and that appears to be due to the selective excit ation of pain fibers. More significantly, in clinical studies, antagonists of the ETA receptor have been shown to ameliorate pain in some patients wit h advanced metastatic prostate cancer. The identification of tumor-associat ed mediators such as ET-1 that might directly or indirectly cause pain in p atients with metastatic disease should lead to improved, targeted analgesia for patients with advanced cancer.