Brain research bulletinFeb 19, 2026

Changes in Brain Circuits Linking Emotion and Sensation in Chronic Pain and Depression

Psychedelic Science Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 20, 2026

Abstract

Chronic pain and major depressive disorder often co-occur, significantly worsening functional impairment.

The comorbidity of chronic pain and major depressive disorder may arise from deep functional coupling and neural network remodeling.
Key brain regions such as the prefrontal cortex, anterior cingulate cortex, amygdala, hippocampus, insula, and reward system exhibit consistent abnormalities in individuals with both conditions.
These brain regions form a cross-brain network that jointly regulates pain, emotion, and cognition.
An integrated emotion-perception coupling network model is proposed to explain the mechanisms underlying this comorbidity.
Future research is encouraged to utilize multimodal imaging, multi-omics data, and computational modeling for personalized treatment strategies.

Simplified

Chronic pain (CP) and major depressive disorder (MDD) are highly disabling global diseases, and their high comorbidity creates a bidirectional vicious cycle, significantly exacerbating functional impairment and treatment resistance. Multidisciplinary evidence suggests that the comorbid nature arises from deep functional coupling and neural network remodeling between the sensory-pain and emotional systems, rather than merely a symptom overlap. Neuroimaging, animal models, and neuromodulation studies demonstrate that key brain regions, including the prefrontal cortex (PFC), anterior cingulate cortex (ACC), amygdala, hippocampus, insula, and reward system, show consistent abnormalities in the comorbid state, creating a cross-brain network that jointly regulates pain, emotion, and cognition. This paper systematically reviews the central structures, neural circuits, and neurotransmitter regulatory mechanisms of CP-MDD comorbidity and proposes an integrated emotion-perception coupling network model. We highlight the mechanisms and translational potential of multi-pathway intervention strategies, with a focus on neuromodulation techniques (rTMS, tDCS), combined with ketamine, BDNF modulators, and anti-inflammatory drugs. Additionally, it is emphasized that future research must integrate multimodal imaging, multi-omics data, and computational modeling to establish a mechanism-driven personalized stratification system. With the support of high spatiotemporal resolution brain connectomics technology, this will facilitate the transition from a 'symptom control' to a 'mechanism repair' paradigm in treating comorbidities.

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Competing interests

Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

PubMed

Changes in Brain Circuits Linking Emotion and Sensation in Chronic Pain and Depression

Abstract

Full Text

Funding

Competing interests

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