Neurobiological substrates of chronic low back pain (CLBP): a brain [99mTc]Tc-ECD SPECT study

Abstract

Background: Recent neuroimaging studies have demonstrated pathological mechanisms related to cerebral neuroplasticity in chronic low back pain (CLBP). Few studies have compared cerebral changes between patients with and without pain in the absence of an experimentally induced stimulus. We investigated the neurobiological substrates associated with chronic low back pain using [^99mTc]Tc-ECD brain SPECT and correlated rCBF findings with the numeric rating scale (NRS) of pain and douleur neuropathique en 4 questions (DN4). Ten healthy control volunteers and fourteen patients with neuropathic CLBP due to lumbar disc herniation underwent cerebral SPECT scans. A quantitative comparison of rCBF findings between patients and controls was made using the Statistical Parametric Mapping (SPM), revealing clusters of voxels with a significant increase or decrease in rCBF. The intensity of CLBP was assessed by NRS and by DN4.

Results: The results demonstrated an rCBF increase in clusters A (occipital and posterior cingulate cortex) and B (right frontal) and a decrease in cluster C (superior parietal lobe and middle cingulate cortex). NRS scores were inversely and moderately correlated with the intensity of rCBF increase in cluster B, but not to rCBF changes in clusters A and C. DN4 scores did not correlate with rCBF changes in all three clusters.

Conclusions: This study will be important for future therapeutic studies that aim to validate the association of rCBF findings with the pharmacokinetic and pharmacodynamic profiles of therapeutic challenges in pain.

Keywords: Brain SPECT; Chronic low back pain; Douleur Neuropathique 4 Questions; Neurobiological substrate; Numeric rating scale.

Fig. 1

Scatter plot showing no correlation between DN4 and NRS scales for 14 patients (Spearman’s Kendall’s rho 0.357, p = 0.211). DN4 Douleur Neuropathique en 4 Questions; NRS Numeric Rating Scale

Fig. 2

Results of the statistical parametric mapping (SPM) analysis showing brain regions with significant rCBF changes in 14 patients with CLBP, compared to ten healthy controls. The figure shows the overlay of clusters upon T1-weighted magnetic resonance imaging from the SPM template. Images show areas with a significant increase (A, B, D, and E) and decrease (C and F) of the regional cerebral blood flow (rCBF). The significant increase of rCBF was found in clusters A (3D view in D; R occipital lobe and R posterior cingulate gyrus) and B (3D view in E; R anterior prefrontal and dorsolateral frontal lobe). Cluster C presented a decrease of rCBF (3D view in F; bilateral parasagittal and postcentral parietal lobe and R middle cingulate cortex). Table 2 describes the Talairach coordinates. Results are shown in p value less than 0.05, corrected for multiple comparisons. A correlation coefficient with 95% CI according to Kendall’s tau non-parametric rank correlation was used to assess the relationship between the rCBF increase (a, b, d, and e) and decrease (c and f) and the results of the NRS (a–c) and DN4 (d–f) scores. The curved lines show the 95% CI around the regression line. In b, higher NRS scores were inversely and moderately correlated with the intensity of rCBF increase in cluster B (Kendall’s tau =  − 0.445, p = 0.033). In a, c, d, e, and f, there was no significant correlation between rCBF changes and NRS or DN4 scores. NRS Numeric Rating Scale; DN4 Douleur Neuropathique en 4 Questions