The nerves innervating the orofacial region also express cold/mechanical sensitive ion channels like TRPA1, cold sensitive TRPM8, or acid-sensing channels like (ASICs and P2X) (23, 24), which can be directly or indirectly stimulated by H+, ATP (25), lipids (20), growth factors (21, 26), proteases (27–29), or cytokines (30–32) released by the tumor microenvironment. The gene discussed is TRPM8; the disease is neoplasm.