More than 50% of cancer patients develop pain before death: 80% can be treated with drugs, but 20% show a low response or have serious adverse effects. Although non-pharmacological interventions such as neurosurgical procedures have been tested, these alternatives are not a preferred option to treat cancer pain due to their high cost, risk, invasiveness and not always proven efficacy. PAINLESS addresses a core component of pain relief, by using an innovative, evidence-based approach. The objective is to adapt and implement a novel, cost-effective, home-based intervention based on neuromodulation to reduce pain and improve quality of life of cancer patients with chronic pain. On the assumption that treatment of chronic pain can benefit from research on the brain mechanisms of pain, we will first attempt to improve our understanding of the role of central pain modulation. The project will be organized in 3 studies: 1) A cohort, longitudinal study (n=450) to explore whether the biomarkers of central pain modulation mechanisms can be predictive of the future occurrence of chronic pain in cancer patients; 2) A cross-sectional study to characterize and stratify cancer patients with vs. without chronic pain (750 patients with the proposed biomarkers and taking into account a number of moderator variables); 3) A pilot study (n=450) to assess the feasibility an efficacy of at-home delivery of transcranial low intensity electric stimulation (tES) for the palliative care of cancer patients suffering from pain PAINLESS will develop a customized web portal to share knowledge and to improve management of the patients; perform techno-economic analyses and Health Technology Assessment of the solution; analyze the possibilities of implementation in different European healthcare systems and results exploitation; and undertake an ambitious dissemination and communication strategy. We will also propose a wide range of measures to ensure compliance with the highest ethical standars.