Novel mechanisms of bone cancer pain revealed with in vivo GCaMP6s imaging

Cancer pain remains a major area of unmet medical need, with few studies existing in proportion to that need. One common form, affecting 400,000 people each year in the US alone, is associated with skeletal metastases. These pains are typically mechanoceptive in nature and poorly managed by available analgesics. Here, we employed in vivo imaging using GCaMP6s to assess the properties of the nerve fibres that convey bone cancer pains. We find that a subclass of nociceptors, those that are normally mechanically insensitive, are recruited and activated in a rodent model of bone cancer, and this dramatically increases sensory input from the diseased tissue to the central nervous system. The recruitment of these so-called silent afferents was found to be Piezo2-dependent. The unique properties of these silent afferents offer several novel opportunities for targeting metastatic bone pain.