Reliable Biomarkers of Descending Pain Inhibition: CPM and LEP-N2P2 in EEG — a Commentary on Wang et al. (European Journal of Pain, 2025)

Brain Bee — First-Person Introduction

Can we objectively observe descending pain inhibition in the brain in a way that is reproducible, rather than relying only on subjective pain reports?

Reliable Biomarkers of Descending Pain Inhibition in EEG

What the Study Shows

Wang, Zhang, Ye, Carter, Finan, Quigg, Moosa, Elias, and Liu propose a dual-domain framework to assess Conditioned Pain Modulation (CPM) by combining:

1. behavioural CPM (B_CPM) based on pain ratings, and

2. neurophysiological CPM (N_CPM) indexed by reductions in the LEP-N2P2 component of laser-evoked potentials recorded with EEG.

Twenty-seven healthy adults completed two laboratory visits separated by at least one week. Nociceptive laser stimuli were applied to the hand before and after a cold pressor task, allowing assessment of descending inhibitory control across sessions.

Key findings include:

• High responder rates: behavioural CPM was consistent in ~92.6% of participants, while neurophysiological CPM exceeded 74% across key electrodes (C3, C4, Cz).

• Significant correlations between B_CPM and N_CPM at sensorimotor and central sites (ρ ≈ 0.54–0.56).

• Good to excellent test–retest reliability for behavioural CPM (ICC up to ~0.81) and for neurophysiological CPM at Cz (ICC up to ~0.77).

• The earlier temporal N1 component showed mean attenuation but poor reliability and no meaningful correlation with behavioural CPM.

Together, these results support the use of LEP-based cortical markers as reliable complements to behavioural CPM measures.

BrainLatam Reading — APUS (Extended Proprioception)

From our perspective, the attenuation of the LEP-N2P2 does not merely reflect “less pain,” but a shift in the body’s readiness for action. The N2P2 component is strongly tied to nociceptive salience and motor relevance. When its amplitude decreases after CPM, we interpret this as the body entering a state of reduced defensive rigidity, where fewer resources are allocated to preparing protective movement.

Methodologically, the authors’ focus on the first stimulus (S1) of each laser triplet is crucial. S1 is the most salient and least affected by adaptation or temporal summation, making it a cleaner window into how the proprioceptive system reorganises under descending inhibition.

BrainLatam Reading — Tekoha (Extended Interoception)

We understand CPM fundamentally as a test of internal regulatory capacity. The cold pressor challenges the organism, and the subsequent reduction in pain responses elsewhere reflects a reorganisation of interoceptive control.

The contribution of this study is showing that this reorganisation is detectable in two converging domains:

• in subjective experience (behavioural CPM), and

• in a stable cortical signal (N2P2-based N_CPM).

The fact that Cz showed the strongest reliability suggests that midline cortical systems involved in integrative pain regulation provide a more stable readout of descending inhibition than earlier, lateralised sensory components.

Limits of the Study

Several boundaries are important:

• The sample consists of healthy adults, so clinical applicability must be tested in chronic pain populations.

• Neurophysiological CPM, while reliable, was generally less stable than behavioural CPM, indicating room for improvement via single-trial modelling or integration with autonomic measures.

• The N1 component does not emerge as a robust biomarker here, which usefully delineates where future efforts may be less productive.

BrainLatam Translation to the Organic World

BrainLatam translation to the organic world:
We read this study as a meaningful step toward making descending pain inhibition observable, reproducible, and mechanistically grounded. It shows that pain modulation can be tracked simultaneously as lived experience and as cortical regulation, without reducing one to the other.

This dual-domain approach helps move pain science away from a false opposition between “subjective report” and “objective signal,” and toward an integrated view of the body as a self-regulating system.

Open BrainLatam Question

If interoceptive markers such as heart-rate variability, respiration, or electrodermal activity are added alongside LEP-N2P2, can we predict individual responsiveness to analgesic or neuromodulatory interventions before treatment begins?

The body does not need belief to function.
It needs space, movement, and regulation.

Ref.:

Wang, D., Finan, P., Elias, W. J., & Liu, C. (2025). Reliable Biomarkers of Descending Pain Inhibition: A Laser‐Evoked Potential and Behavioural Study. European Journal of Pain, 30(1), e70181–e70181. https://doi.org/10.1002/ejp.70181