# Recent progress in chronic pain-related negative emotions and cognitive dysfunction: insights into the mechanisms underlying neural circuitry

## TL;DR

This paper reviews recent findings on how chronic pain is linked to negative emotions and cognitive issues through specific brain circuits.

## Contribution

The paper provides a novel synthesis of neural circuit mechanisms underlying chronic pain and its comorbid emotional and cognitive dysfunctions.

## Key findings

- Chronic pain activates or inhibits specific brain circuits linked to anxiety, depression, and cognitive dysfunction.
- Brain regions like the amygdala, thalamus, and lateral habenula are central to these pain-related emotional and cognitive changes.

## Abstract

Pain is a complex sensory and affective experience that is frequently accompanied by comorbid conditions such as anxiety, depression, fear, and cognitive dysfunction, collectively exacerbating patient suffering and disease burden. Despite significant advancements in pain research, the mechanisms underlying chronic pain and its related negative emotions remain inadequately understood. The cerebral cortex, lateral habenula (LHb), thalamus, amygdala, parabrachial nucleus (PBN), hippocampus, and locus coeruleus (LC) are widely associated with chronic pain, chronic pain-related negative emotions, and cognitive dysfunction. In this review, we summarize recent research on the functions of various brain nuclei and their subregions in chronic pain and related negative emotions and cognitive dysfunction from the perspective of neural circuits. By delineating these circuit-level mechanisms, we aim to provide insights that may inform the development of more effective strategies for the clinical diagnosis and treatment of chronic pain and comorbid emotional and cognitive dysfunctions.

Chronic pain (pathological neuropathic pain models and chronic inflammatory pain models) induces the generation and development of anxiety, depression, fear, aversion, and cognitive impairments by activating/inhibiting specific neural circuits in the brain.Illustration of brain pathways associated with pain, showing connections to regions involved in anxiety, aversion, cognitive dysfunction, depression, and fear. Arrows indicate signal pathways between peripheral pain receptors, spinal cord, and various brain areas. Key brain regions such as the cortex, thalamus, amygdala, and different cortical and subcortical structures are labeled. Color-coded lines represent different emotional and cognitive responses linked to pain. A small diagram shows peripheral receptors connected to the spinal cord.

Chronic pain (pathological neuropathic pain models and chronic inflammatory pain models) induces the generation and development of anxiety, depression, fear, aversion, and cognitive impairments by activating/inhibiting specific neural circuits in the brain.