The Role of Corticolimbic Circuitry in Chronic Pain

Chronic pain is one of the most common clinical symptoms and has been considered as a global healthcare problem. Currently, the underlying mechanisms of the transition from acute to chronic pain, also known as pain chronification, still remain incompletely understood. Neuroimaging studies indicated that the corticolimbic circuitry (prefrontal cortex, amygdala, hippocampus, nucleus accumbens, ventral tegmental area) is preferentially involved in encoding fluctuations of ongoing pain for various chronic pain conditions, suggesting the critical role of this neural circuitry in pain chronification. In this review, we first summarized the emotion, motivation, and memory dysfunctions and their corresponding structural and functional changes of the corticolimbic circuitry in chronic pain patients. Then, we reviewed the longitudinal brain imaging studies on low back pain chronification and highlighted the neuroimaging variables (i. e., the structural and functional properties of the corticolimbic circuitry) that could predict the transition from acute to chronic pain. For example, the functional connectivity between the medial prefrontal cortex and nucleus accumbens/hippocampus, as well as the functional connectivity between the dorsal medial prefrontal cortex and amygdala/nucleus accumbens could predict the development of chronic pain 1 year later. Besides, based on the existing theoretical model of chronic pain, we emphasized the critical role of the reinforcement learning of negative emotions as well as the dysfunctions of reward and stress systemin pain chronification. Finally, we pointed out the limitations of previous studies in this field and suggested future research directions for a better understanding of the neural mechanisms of chronic pain and pain chronification