Capsaicin-mediated Denervation of Sensory Neurons Promotes Mammary Tumor Metastasis to Lung and Heart

Capsaicin specifically activates or destroys small diameter nociceptive sensory neurons that contain the capsaicin receptor, also called vanilloid receptor 1. Neurons sensitive to capsaicin mediate inflammatory pain and are important targets for management of chronic pain. These neurons also regulate local tissue homeostasis, inflammation, healing and development, especially under conditions of psychological stress. Stress contributes to increased cancer recurrence and metastasis through as yet undefined mechanisms. Likewise, activity of capsaicin-sensitive neurons is altered by pathological conditions that may lead to metastatic growth (e.g. stress). Therefore, we examined effects of a treatment that induces sensory nerve denervation on breast cancer metastases. Systemic denervation of sensory neurons caused by treatment with 125 mg/kg capsaicin resulted in significantly more lung and cardiac metastases in adult mice injected orthotopically with syngeneic 4T1 mammary carcinoma cells than was observed in vehicle-treated controls. Heart metastases, normally very rare, occurred as pericardial nodules, intra-myocardial nodules, or combined pericardial-myocardial lesions. Since the rate of primary tumor growth was unaffected, effects on metastases appear to be host tissue-specific. Although preliminary, these observations provide one possible explanation for resistance of cardiac tissue to tumor involvement and highlight contributions of host tissue, including sensory neurons, in the efficiency of cancer metastasis.