<p>The word “pain” is commonly used in reference to a variety of physical and psychological states that share negative hedonic components. This paper reviews evidence that suggests that physical pain (real or potential tissue damage) and psychological pain (frustration induced by unexpected reward loss) share psychobiological mechanisms. We first analyze the consummatory successive negative contrast (an animal model of frustration and reward loss), and describe behavioral, pharmacological, and neurobiological evidences that relates it to physical pain. Experimental procedures used to induce frustration in humans are also reviewed, including studies that directly relate reward loss events and physical pain. Finally, we ponder the limitations of this research line and its contributions to identify the psychobiological basis and the clinical impact of psychological pain, with a reference to the current COVID-19 pandemic, a global experience of loss with health, economical, social and psychological consequences</p>