Chronic Pain: Structural and Functional Changes in Brain Structures and Associated Negative Affective States

Abstract

Chronic pain is a condition in which pain progresses from an acute to chronic state and persists beyond the healing process. Chronic pain impairs function and decreases patients' quality of life. In recent years, efforts have been made to deepen our understanding of chronic pain and to develop better treatments to alleviate chronic pain. In this review, we summarize the results of previous studies, focusing on the mechanisms underlying chronic pain development and the identification of neural areas related to chronic pain. We review the association between chronic pain and negative affective states. Further, we describe the structural and functional changes in brain structures that accompany the chronification of pain and discuss various neurotransmitter families involved. Our review aims to provide guidance for the development of future therapeutic approaches that could be used in the management of chronic pain.

Keywords: central sensitization; chronic pain; corticolimbic system; negative affective state; neurotransmitter.

Figure 1

Ascending pathway (red line): A nerve pathway that projects upwards from the spinal cord to the brain carrying sensory information from the body to the brain. Pain signals ascend from the spinal dorsal horn to the rostral ventral medulla (RVM) and periaqueductal grey matter (PAG). Pain signals are then transmitted to the thalamus, where they are sent to higher brain centers, such as the primary and secondary somatosensory cortices (S1/S2), prefrontal cortex (PFC), anterior cortex (ACC), amygdala (AMG), and nucleus accumbens (NAc). Descending pathway (blue line): A nerve pathway that descends down the spinal cord and has a role in the modulation of pain, involving important areas of the brainstem such as the RVM, PAG, and locus coeruleus (LC).