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.