Pain is among the most common medical complaints, and is associated with impaired quality of life of affected individuals and consequent large societal costs. Taking into account the multidimensional nature of pain, this paper describes the concept of the pain mental state vector, which integrates affective, cognitive, physiological, and motor representations. Bottom-up pain pathways and descending pain modulatory pathways are briefly reviewed, before discussing top-down multimodal cognitive regulation of pain. Due to empirical success of pain management that relies on attentional distraction facilitated by Virtual Reality (VR), as well as prior literature on the underlying neurobiological mechanisms, the paper also discusses some aspects of the neurobiology of multimodal cognitive regulation of pain.