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The Sciatic Nerve Cuffing Model of Neuropathic Pain in Mice

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Neuromodulation of the Cingulate Cortex for Pain.

Andrew Strohman^1,2,3, Wynn Legon^1,3,4,5,6,7

¹Fralin Biomedical Research Institute at Virginia Tech Carilion, Roanoke, VA, USA.

The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry

|June 27, 2025

Summary

This review explores non-invasive neuromodulation for pain by examining distinct anterior cingulate cortex subregions (sACC, pACC, aMCC). It highlights techniques like TMS, TES, and LIFU for targeted pain relief.

Keywords:

cingulate cortex neuromodulation pain transcranial electric stimulation transcranial magnetic stimulation transcranial ultrasound stimulation

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Area of Science:

Neuroscience
Pain Research
Neuromodulation

Background:

The subgenual (sACC), pregenual (pACC) anterior cingulate, and anterior midcingulate (aMCC) cortices are key in pain processing.
These regions are potential targets for non-invasive neuromodulation.

Purpose of the Study:

To review the function and connectivity of sACC, pACC, and aMCC in acute and chronic pain.
To compare non-invasive neuromodulation techniques (TMS, TES, LIFU) for targeting these deep midline structures.
To examine factors influencing analgesic outcomes, including placebo effects and stimulation context.

Main Methods:

Literature review synthesizing evidence on cingulate cortex subregions in pain.
Comparative analysis of neuromodulation techniques (TMS, TES, LIFU).
Exploration of functional connectivity and personalized targeting strategies.

Main Results:

sACC, pACC, and aMCC show distinct roles in sensory, affective, and autonomic pain components.
Different neuromodulation techniques have unique strengths and limitations for accessing these targets.
Technique- and target-specific effects, alongside placebo mechanisms, modulate pain relief.

Conclusions:

Non-invasive neuromodulation offers promising therapeutic potential for pain by targeting specific cingulate cortex subregions.
Personalized, connectivity-based targeting strategies are emerging to enhance precision and overcome limitations.
Further research is needed to optimize neuromodulation for effective and individualized pain management.