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Pain has a strong negative impact on overall quality of life, affecting daily activities, social interactions, and mental health. It is estimated that 12-48% of European adults suffer from chronic pain at any one moment. However, current treatments often remain inadequate and hampered by limitations (e.g., side effects, addiction, tolerance). There is an urgent need for new, non-invasive, pain management strategies. Growing evidence provides support for transcutaneous auricular vagus nerve stimulation (taVNS) as a promising new treatment option. Clinical trials and animal studies have shown significant improvements in pain symptoms. However, drawing firm conclusions from these studies is difficult, given the variability in samples, pain outcomes and methodologies. There is a critical lack of systematic and well-controlled studies on the efficacy of taVNS for pain relief in healthy individuals, combined with an urgent need for standardized stimulation protocols and longitudinal assessments. In this project, we address these challenges in a series of three studies that systematically investigate the efficacy and mechanisms of taVNS effects on experimental pain in a healthy population. In Study I, we will identify the optimal stimulation parameters (in particular, frequency and pulse width) resulting in the greatest pain relief. Study II compares different control conditions, to disentangle the effects of taVNS from non-specific stimulation as well as expectation effects. And finally, in Study III, we will explore potential long-term effects of taVNS in a longitudinal intervention study using an innovative multi-modal approach, integrating ecological momentary assessments, wearable sensors and repeated self administered stimulation at home. In all three studies, autonomic nervous system activity will be monitored (e.g., heart rate, electrodermal activity) and psychological factors will be assessed. We will employ a comprehensive battery of pain outcomes, including several modalities of pain thresholds, as well as dynamic pain measures (e.g., conditioned pain modulation and temporal summation). The primary aim of the project is to provide an evidence-based framework for applying taVNS in pain research and to establish empirically tested standardized protocols for future clinical investigations. We will formulate methodological recommendations regarding study design and stimulation parameters to both the research and clinical community. These will enable more meaningful and reproducible results and facilitate the progress in taVNS research for pain management. Importantly, the project will also provide insight into the underlying mechanisms of taVNS. Addressing the gaps and challenges in the literature on experimental pain in healthy individuals is a critical first step in the translation towards clinical therapeutic taVNS interventions.