Cross-sectional relationships between spinal cord gray matter volume and pain in individuals with fibromyalgia and opioid use

Abstract

Brain gray matter volume (GMV) has been extensively examined in chronic pain and opioid therapy, but spinal GMV has not. As a first investigation of spinal cord GMV in chronic pain and opioid therapy, as our primary outcome, we compared averaged C5-C7 GMV of the spinal cord dorsal/ventral horns among 3 female cohorts: controls (CON, n = 30), and individuals with fibromyalgia taking opioids (FMO, n = 27) and not taking opioids (FMN, n = 31). After adjusting for age across the 3 groups (and adjusting for both age and pain duration across the FM patients), we observed differences in dorsal and ventral horn GMVs, with less GMV in FMOs vs. controls. Additionally, we evaluated within-group relationships between GMVs and clinical pain measures. Among FMNs, dorsal (D) and ventral (V) horn GMVs were positively associated with pain duration (D: p = 0.042, V: p = 0.015). Among FMOs, GMV was positively associated with pain severity (D: p = 0.028, V: p = 0.012), pain interference (D: p = 0.010, V: p = 0.004), and cold pain tolerance (D: p = 0.004, V: p < 0.001). Together with distinct within-group pain-related correlations between FMN and FMO cohorts, less spinal cord GMV in the opioid-taking FM patients suggests spinal cord GMV may be influenced by long-term opioid use in FM.

Keywords: Cold pain tolerance; MRI; Opiates; Spine.

Fig. 1

Gray matter volume (GMV) across groups. Group-stratified distributions are shown for mean C5-C7 (A) ventral and (B) dorsal horn grey matter volume. Tukey pairwise comparisons indicate statistically significant differences (p < 0.05) between groups at a univariate level for the CON vs. FMO group comparison. FMO individuals with fibromyalgia taking opioids; FMN individuals with fibromyalgia not taking opioids, CON controls.

Fig. 2

Associations between gray matter volume and pain severity/interference. Group-stratified results are shown for bivariate associations between mean C5 – C7 ventral and dorsal horn gray matter volume, average pain severity, and average pain interference. Correlations between ventral horn gray matter volume (GMV) and pain severity and interference are represented in Panels A and B, respectively. Correlations between dorsal horn GMV and pain severity and interference are represented in Panels C and D, respectively. FMO individuals with fibromyalgia taking opioids; FMN individuals with fibromyalgia not taking opioids, Rs Spearman’s correlation coefficient. Statistical significance threshold set at p < 0.05. Lines representing the correlation trends that met this threshold are solid and bold.

Fig. 3

Associations between gray matter volume and cold pain tolerance. Group-stratified results are shown for bivariate associations between mean C5 – C7 ventral (A) and dorsal (B) horn gray matter volumes (GMVs) vs. cold pressor test (CPT) submersion time in seconds. (C) Combined boxplot and violin plots are shown for group-stratified distributions of CPT submersion time in seconds. FMO individuals with fibromyalgia taking opioids; FMN individuals with fibromyalgia not taking opioids, CON controls, Rs Spearman’s correlation coefficient. Statistical significance threshold set at p < 0.05. Lines representing the correlation trends that met this threshold are solid and bold.

Fig. 4

Associations between gray matter volume and pain duration. Group-stratified results are shown for bivariate associations between mean C5 – C7 ventral (A) and dorsal (B) horn gray matter volumes (GMVs) and average pain duration in years. FMO = individuals with fibromyalgia taking opioids; FMN individuals with fibromyalgia not taking opioids, Rs Spearman’s correlation coefficient. Statistical significance threshold set at p < 0.05. Lines representing the correlation trends that met this threshold are solid and bold.

Fig. 5

Schematic of spinal cord gray matter volume analysis pipeline. Spinal cord preprocessing was performed using the Spinal Cord Toolbox. Images from a control participant were used to create the graphics for this figure. Panel A shows the PAM50 T₂ -weighted template and the vertebral level masks. Panel B shows the template to T₂-weighted structural image registration process. Panel C shows the process of segmenting the spinal cord gray matter. Gray matter volume (GMV) was extracted from the top of the C5 vertebra to the bottom of the C7 vertebra, and total horn GMVs were computed as left and right sums for each horn. D Dorsal, S Superior, V Ventral, R Right.