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Psychophysically-anchored, Robust Thresholding in Studying Pain-related Lateralization of Oscillatory Prestimulus Activity

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The Human Dorsolateral Prefrontal Cortex in Pain and Pain Modulation: A Review and Activation-Likelihood Estimation

Lewis S Crawford¹, Damien C Boorman^1,2, James W M Kang¹

¹School of Medical Sciences (Neuroscience), the Brain and Mind Centre, University of Sydney, Camperdown, Australia.

European Journal of Pain (London, England)

|June 24, 2026

Summary

This study reveals that the dorsolateral prefrontal cortex (dlPFC) engages similar subregions for both perceiving and inhibiting pain, including placebo analgesia. These findings pinpoint specific dlPFC areas crucial for pain processing and modulation, guiding targeted neuromodulation therapies.

Keywords:

dorsolateral prefrontal cortex endogenous analgesia magnetic resonance imaging pain placebo analgesia

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Area of Science:

Neuroscience
Pain Research
Cognitive Neuroscience

Background:

The dorsolateral prefrontal cortex (dlPFC) is recognized for its role in pain perception and modulation.
However, specific dlPFC subregions involved in these processes remain unclear.
This review aims to precisely map dlPFC activity across various pain states.

Purpose of the Study:

To precisely map dlPFC subregions engaged during acute pain, chronic pain, and pain modulation.
To identify common and distinct dlPFC activation patterns across different pain conditions.
To refine understanding of dlPFC's role in pain perception and modulation.

Main Methods:

A meta-analysis of neuroimaging studies focusing on dlPFC activation.
Activation Likelihood Estimation (ALE) used to analyze data from over 4000 participants.
Examined dlPFC engagement in acute pain, chronic pain, placebo analgesia, conditioned pain modulation, and offset analgesia.

Main Results:

Similar dlPFC activation patterns (Brodmann areas 8, 9, 46) observed in acute pain, chronic pain, and placebo analgesia.
No significant laterality effect was found; both hemispheres were engaged.
Offset analgesia and conditioned pain modulation showed preferential engagement of specific Brodmann areas (8/45 and 9/46, respectively).

Conclusions:

Pain perception and placebo-induced pain inhibition engage overlapping, focused areas within the dlPFC.
These findings highlight specific dlPFC targets for therapeutic interventions.
This research strengthens the rationale for dlPFC-focused neuromodulation in pain management.