Background & Aims

Chronic pain is correlated with gray matter anomalies in the brain. Prior studies have reported widespread reductions in cortical and subcortical volume, as well as cortical surface area, in individuals with chronic pain compared to those without pain. A recent publication by Bhatt et al. [1] and our accompanying work [2] show these patterns to be consistent across different chronic pain conditions. In the present study, we examine evidence for reversal in pain-related gray matter anomalies.

Methods

We used longitudinal data from 40,000 U K Biobank participants, grouping them into one of four trajectories: unresolved, resolved, new chronic pain, and pain-free controls. Pain status was assessed at two visits, minimum four years apart; the second visit included brain imaging. For each trajectory, cases were assigned based on presence of chronic pain (minimum 3 months’ duration) at one or more of eight body site categories: head, face, neck/shoulder, back, stomach, hip, knee, and widespread. For each region of interest (ROI), we calculated pairwise differences in mean ROI value per pain trajectory, adjusted for demographic and scanner measures. We then calculated a Reversibility Index, RI, defined as the ratio of differences in regions with gray-matter decrements between resolved and unresolved and between controls and unresolved groups. An RI of 1 indicates complete reversal; an RI<1 indicates incomplete reversal, and an RI>1 indicates increase in brain tissue upon recovery.

Results

The RI was close to 1 for volumes in the diencephalon and most cortical ROIs, including the somatosensory cortex and insula, which are consistently reported as important pain-processing regions. At the level of the surface area, the RI was >1 for the somatosensory cortex and insula. It was likewise >1 in the gray matter volumes of the amygdala, pallidum, and the hippocampus, as well as in several temporal and occipital regions. Several regions, such as the cerebellum cortex and the somatosensory cortex, showed gradual reduction in gray matter volume across resolved to new to unresolved pain, which suggests an exacerbating effect of chronic pain duration.

Conclusions

Our findings suggest that certain key brain regions involved in pain processing, such as the somatosensory cortex and insula, may undergo reversible changes in chronic pain. Additionally, subcortical regions such as the hippocampus and amygdala, which have reported correlations with pain chronification, appear to undergo a reduction during chronic pain that is replaced by an increase after pain resolution. This supra-compensatory reversal suggests a role for neuroplasticity that accompanies recovery from pain in affected brain regions.

References

[1] Bhatt RR, Haddad E, Zhu AH, Thompson PM, Gupta A, Mayer EA, Jahanshad N. Mapping brain structure variability in chronic pain: the role of widespreadness and pain type and its mediating relationship with suicide attempt. Biological psychiatry. 2023 Aug 4.
[2] Bango C, Zorina-Lichtenwalter K, Ceko M, Rader L, Lindquist MA, Friedman NP, Wager TD. Neural Correlates of Chronic Pain Trajectories in the UK Biobank. Poster submitted to IASP 2024.

Presenting Author

Katerina Zorina-Lichtenwalter

Poster Authors

Katerina Zorina

PhD

University of Colorado Boulder

Lead Author

E-mail

Carmen Bango

BA

Oregon Health & Science University

Lead Author

E-mail

Marta ?eko

PhD

University of Colorado Boulder

Lead Author

E-mail

Lydia Rader

MA

University of Colorado Boulder

Lead Author

E-mail

Bogdan Petre

MS

Dartmouth College

Lead Author

E-mail

Martin Lindquist

PhD

Johns Hopkins University

Lead Author

E-mail

Naomi Friedman

PhD

University of Colorado Boulder

Lead Author

E-mail

Tor Wager

Dartmouth College

Lead Author

E-mail

Topics

  • Pain Imaging