<p>The creation of virtual brains has long attracted the attention of the scientific community. Over time, various projects have aimed to produce brain simulations of varying complexity. These scientific efforts have often been accompanied by lively philosophical debates highlighting the ethical implications of brain simulations, such as their moral status, the possibility of developing consciousness and personhood, and concerns about unethical experimentation. In particular, the possibility that a highly complex virtual brain could experience pain has been a central concern, especially in the context of the Human Brain Project. This paper presents a conceptual analysis that traces the legacy of this debate and situates it within the current scientific context. The issue warrants renewed attention for two reasons. First, the literature has generally treated pain as an abstract concept, without situating it within a specific theoretical framework. Second, recent technologies for medical purposes, such as digital brain twins, promise to connect virtual brains with their biological brains, offering new perspectives on the question of pain. Adopting a mixed conception of pain that integrates the sensory and affective dimensions, two requirements for experiencing pain can be extrapolated. These requirements are then implemented in a comparative conceptual analysis to examine three different virtual brain architectures. The findings suggest that, from a theoretical standpoint, highly advanced virtual brains connected in real time to their biological counterparts could experience psychological pain. </p>