Chronic and neuropathic pain, usually diagnosed as spontaneous pain, hypersensitivity to pain or both, is a maladaptive response of the organism to injury and inflammation.Finding new effective drugs to treat these debilitating conditions has shown particularly difficult, as compounds showing good efficacy in preclinical models often fail to meet clinical trials endpoints. A commonly accepted explanation for this discrepancy is that virtually all preclinical analgesic tests have only limited predictability, as they are based on models of evoked pain, whereas patients mainly seek relief of spontaneous pain.To fill the gap in our knowledge of the mechanism of spontaneous pain and to accelerate the discovery process towards better analgesics, we propose to implement a new in vivo platform for deciphering pain pathways in animal models of spontaneous pain. A new electrophysiological approach, high throughput microneurography (HT-MNG) will be implemented by using in house nanotechnology and microelectronics. This approach will be combined with in vivo RNA interference and optogenetics and validated by specifically addressing targets known to be involved in chronic and neuropathic pain conditions.The proposed preclinical in vivo platform has a great translational potential, as HT-MNG recordings from animal models will provide data directly comparable to those from human patients. Thus, we expect our project to significantly contribute in avoiding expensive failures in Phase II and Phase III pain studies due to lack of drug efficacy. Moreover, by opening the possibility to measure and recognize specific excitability patterns in peripheral neuropathies, the project can help identify patients more likely to respond to a particular drug, dose or regime, thus opening new opportunities for personalized medicine.