Deep brain stimulation mechanisms in comorbid pain and emotional dysregulation from animal models.

Authors

Tian-En Si, Hao Han, Ying-Ying Zhang, Zhen Zhou, Zhi-Xiao Li, Jing Cao, Wei Dong Zang

Published in

iScience. Volume 29. Issue 10. Pages 117569. Oct 16, 2026. Epub Sep 23, 2026.

Abstract

Deep brain stimulation (DBS) is a potent neuromodulatory intervention for chronic pain and comorbid affective disorders. This review synthesizes preclinical evidence detailing the neural circuits and molecular cascades engaged by DBS in models of pain and emotional dysregulation. We delineate how DBS-targeting regions like the prefrontal cortex (PFC), thalamus, and nucleus accumbens (NAc) recruit the prefrontal-midbrain-spinal axis to facilitate endogenous opioid release and modulate neurotransmission, thereby attenuating nociception. Concurrently, stimulating the ventromedial PFC (vmPFC) or lateral habenula (LHb) ameliorates affective deficits by restoring serotonergic (5-HT) and dopaminergic (DA) tone and stabilizing circuit dynamics. By mapping these convergent and divergent mechanisms, we highlight how DBS fine-tunes reward, anti-reward, and descending antinociceptive pathways. This mechanism-based framework outlines a translational roadmap for personalized neuromodulation, guiding symptom-specific target selection and the development of biomarker-driven, closed-loop DBS systems to concurrently treat pain and affective pathologies.

PMID:
42831145
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.