In conclusion, our present findings demonstrate that the creation of acidic extracellular bone micro-environments by HNSCC via lactic acid production through plasma membrane MCT4 and the responses of the sensory neurons innervating bone to the acidic microenvironment via TRPV1 are critical contributors to the pathophysiology of HNSCC-BP. Here, TRPV1 is linked to head and neck squamous cell carcinoma.