Sleep and pain: recent insights, mechanisms, and future directions in the investigation of this relationship

Sleep disturbances and chronic pain are considered public health concerns. They are frequently associated, and the direction of its relationship and possible mechanisms underlying it are frequently debated. The exploration of the sleep-pain association is of great clinical interest to explore in order to steer potential therapeutic avenues, accommodate the patient's experience, and adapt the common practice of health professionals. In this review, the direction between sleep-pain in adult and pediatric populations will be discussed. Moreover, the possible mechanisms contributing to this relationship as endogenous pain modulation, inflammation, affect, mood and other states, the role of different endogenous substances (dopamine, orexin, melatonin, vitamin D) as well as other lesser known such as cyclic alternating pattern among others, will be explored. Finally, directions for future studies on this area will be discussed, opening up to the addition of tools such as brain imaging (e.g., fMRI), electrophysiology and non-invasive brain stimulation techniques. Such resources paired with artificial intelligence are key to personalized medicine management for patients facing pain and sleep interacting conditions.