The circuit basis for chronic pain and its comorbidities

Chronic pain is poorly treated with many developing disabling comorbidities such as anxiety, depression and insomnia. Considerable evidence supports the idea that pain and anxiodepressive disorders share a common neurobiology and can mutually reinforce, which has significant long-term implications as the development of comorbidities leads to poorer treatment outcomes for both pain and mood disorders. This article will review recent advances in the understanding of the circuit basis for comorbidities in chronic pain.

A growing number of studies have aimed to determine the mechanisms underlying chronic pain and comorbid mood disorders by using modern viral tracing tools for precise circuit manipulation with optogenetics and chemogenetics. These have revealed critical ascending and descending circuits, which advance the understanding of the interconnected pathways that modulate the sensory dimension of pain and the long-term emotional consequences of chronic pain.

Comorbid pain and mood disorders can produce circuit-specific maladaptive plasticity; however, several translational issues require addressing to maximise future therapeutic potential. These include the validity of preclinical models, the translatability of endpoints and expanding analysis to the molecular and system levels.