Neuropathic pain is a frequent feature of peripheral neuropathy adversely impacting patients’ quality of life and increasing health care costs. Not all individuals with neuropathy develop pain and it is not possible to predict who is more or less susceptible among those with similar risk exposure. Inability to identify high-risk individuals and drug-responder patients and lack of drugs acting on target sites for which there is strong evidence of pathogenicity explain the disappointing effect of current treatments. The PROPANE STUDY aims to address these issues through a solid clinical and genetic approach employing an innovative technological platform. The main objectives are to resolve the genetic architecture of painful neuropathy achieving a stratification of high-risk neuropathic pain patients by novel biomarkers, to deepen understanding of underlying mechanisms and druggable targets and to identify new molecules tailored to potentially drug-responder patients and determine their effects in pre-clinical settings. Results will advance the field beyond the current state-of-the-art opening a window upon a validated individualized pain medicine and having an innovative impact both on patients’ care and market applications. These aims will be achieved by a complementary approach based on targeted sequencing of the 5 sodium channel genes expressed in the nociceptive pathway and identification of new targets by unbiased whole exome sequencing and transcriptome assay. Melding of these two approaches offers a close-to-optimal balance between highly-focused, challenging but clearly achievable goals (sodium channels in pain) and a broader unbiased approach that will capture and deliver other targets and approaches from our unique patient population. Our strong preliminary findings were the departure point of the PROPANE STUDY and the expected results could be translated into solutions able to benefit a large population of pain patients in terms of diagnosis and treatment.