Background & Aims
Grey matter (GM) changes are often observed in people with chronic low back pain (cLBP).(1) These GM adaptations may be reversed with treatment, at least partially.(2) Pain Reprocessing Therapy (PRT), a promising new psychological intervention, reduces brain responses to evoked back pain and increases resting connectivity.(3) Whether PRT affects GM adaptations remains unexplored. This study aimed to determine i) whether GM alterations observed in at pre-treatment for cLBP patients relative to healthy controls can be reversed by PRT and ii) whether PRT leads to GM changes not observed as baseline differences relative to healthy controls.(3)
Methods
N=151 cLBP patients (54% women) were randomly assigned to PRT, open-label placebo injection (subcutaneous saline), or usual care.(3) Participants in PRT completed 8 individual 1-hour PRT sessions for 4 weeks (PRT content is described elsewhere).(3) Primary outcomes here were defined by performing a whole-brain cross-sectional voxel-based morphometry (VBM) using CAT12 comparing pre-treatment cLBP patients to age- and gender-matched pain-free controls (n=52; 55% women). Summarized parameter estimates for GM extracted from each region showing cLBP vs. healthy control group differences were submitted to a linear mixed model with treatment (PRT, open-label placebo, treatment as usual) and timepoint (pre-, post-treatment). Finally, a whole-brain analysis was performed using the SwE toolbox to detect whether any additional GM change was observed for PRT vs. both control groups. TFCE correction was performed (pFWEc < 0.05) followed by an exploratory uncorrected threshold (p < .005, k = 50).
Results
PRT led to large reductions in reported pain intensity relative to controls. TFCE-corrected cross-sectional analysis did not reveal between-group differences in GM. At an uncorrected threshold, 5 clusters were observed: cLBP vs. healthy control showed less GM in superior parietal, occipital and postcentral gyrus as well as greater GM in the temporal lobe and dorsal precuneus. GM estimates in these 5 clusters did not correlate with any clinical features in the cLBP group, p > .05. No change was observed after PRT (compared to either control group) in any of these 5 clusters. However, the whole-brain longitudinal analysis did show that cLBP patients assigned to PRT had a decrease of GM in the calcarine cortex and the PCC compared to the patients in the usual care group.
Conclusions
To the best of our knowledge, this is the largest RCT examining treatment effects on GM alterations in people with chronic pain to date. Our results question the extent and relevance of GM alterations in people with cLBP. GM adaptations were subtle in this sample, and changes in GM were not observed despite large reported pain reductions. Future research should investigate whether GM adaptation are more evident in cLBP patients with greater disability and whether GM changes are observed at longer post-treatment follow-up.
References
1Henn, A. T. et al. Structural imaging studies of patients with chronic pain: an anatomic likelihood estimate meta-analysis. Pain, 10.1097 (2022).
2Murillo, C. et al. Grey matter adaptations to chronic pain in people with whiplash-associated disorders are partially reversed after treatment: A voxel-based morphometry study. The Journal of Pain (2024).
3Ashar, Y. K. et al. Effect of pain reprocessing therapy vs placebo and usual care for patients with chronic back pain: a randomized clinical trial. JAMA psychiatry 79, 13-23 (2022).