Patients suffer from mechanical hyperalgesia, which causes strong pain from minor mechanical stimuli after surgery, trauma. Nonsteroidal anti-inflammatory analgesics, opioids, and nerve block therapy have been used to treat mechanical hyperalgesia. Side effects of NSAIDS, such as peptic ulcers and renal dysfunction, are problematic. Nerve block therapy must be administered by technically skilled medical personnel. Opioids often suffer from serious central nervous system side effects such as nausea and respiratory depression. Furthermore, opioids are not good at relieving pain caused by mechanical stimuli and cannot adequately reduce mechanical hyperalgesia. Thus, no effective and safe treatment for mechanical hyperalgesia has yet been established. This is due to the fact that the molecular mechanism of mechanical hyperalgesia is not well understood. We have identified a novel molecule, Tmem45b, which we have been studying to identify the molecule responsible for mechanical hyperalgesia. Tmem45b is a novel pain-related molecule that is not involved in pain perception under normal conditions but causes mechanical hyperalgesia induced by skin incision or inflammation. Furthermore, we have confirmed that Tmem45b is a molecule that is selectively expressed in the peripheral nervous system, and targeting Tmem45b may be able to treat mechanical hyperalgesia without causing central side effects. In this symposium, we will introduce the research process leading up to the discovery of Tmem45b and our current efforts for its application to humans.