Analgesic efficacy of bradykinin B₁ antagonists in a murine bone cancer pain model

Cancer pain is a significant clinical problem because it is the first symptom of disease in 20% to 50% of all cancer patients, and 75% to 90% of patients with advanced or terminal cancer must cope with chronic pain syndromes related to failed treatment and/or tumor progression. One of the most difficult to treat cancer pains is metastatic invasion of the skeleton that can generate ongoing and bone breakthrough pain, which represents one of the most debilitating cancer-related events. Because bradykinin has been shown to be released in response to tissue injury and plays a significant role in driving acute and chronic inflammatory pain, we focused on bradykinin antagonists in a model of bone cancer pain. In our model of bone cancer, which involves the injection and confinement of 2472 sarcoma cells to the mouse femur, pharmacologic blockade of the bradykinin B₁ receptor is effective in reducing pain-related behaviors at both early and advanced stages of bone cancer. Perspective: Bone cancer pain can be severe and difficult to control fully. With a mouse model of bone cancer pain we demonstrate that pharmacologic blockade of the bradykinin B₁ receptor is effective in reducing bone cancer pain-related behaviors, suggesting that B₁ antagonists might be useful in attenuating bone cancer pain in humans.