IL6 and neoplasm: Finally, in BM, tumor acidosis is also responsible for pain induction via the direct stimulation of ion-sensitive nociceptors on the cell membrane of sensory neurons, and by promoting hyperalgesia through the induction of the release of neuromodulators (e.g., the brain-derived neurotrophic factor (BDNF), IL-6, IL-8) in tumor-associated mesenchymal stromal cells [9,14].