Phenotype Matters

Abstract

Studies have associated chronic low back pain (cLBP) with grey matter thinning. But these studies have not controlled for important clinical variables (such as a comorbid affective disorder, pain medication, age, or pain phenotype), which may reduce or eliminate these associations. We conducted cortical thickness and voxel-based morphometry (VBM) analyses in 14 cLBP patients with a discogenic component to their pain, not taking opioids or benzodiazepines, and not depressed or anxious. They were age and gender matched to 14 healthy controls (HCs). An ROI-driven analysis (regions of interest) was conducted, using 18 clusters from a previous arterial spin labeling study demonstrating greater regional cerebral blood flow (rCBF) in these cLBP subjects than the HCs. Cortical thickness and VBM-based gray matter volume measurements were obtained from a structural MRI scan and group contrasts were calculated. MANOVA showed a trend toward cortical thickening in the right paracentral lobule in cLBP subjects (F(1,17)=3.667, p<0.067), and significant thickening in the right rostral middle frontal gyrus (F(1,17)=6.880, p<0.014). These clusters were non-significant after including age as a covariate (p<0.891; p<0.279). A whole-brain cortical thickness and VBM analysis also did not identify significant clusters of thinning or thickening. Exploratory analyses identified group differences for correlations between age and cortical thickness of the right rostral middle frontal gyrus (cLBP: R=-0.03, p=0.9; HCs: R=-0.81, p<0.001), i.e., HCs demonstrated age-related thinning while cLBP patients did not. Our pilot results suggest that controlling for affect, age, and concurrent medications may reduce or eliminate some of the previously reported structural brain alterations in cLBP.

<p>Altered intrinsic brain activity in patients with toothaches using the amplitude of low-frequency fluctuations: a resting-state fMRI study</p>

“…In previous studies, Li et al28 reported that brain areas, including bilateral paracentral lobule and the right thalamus were activated by acupuncture treatments. Erpelding et al29 found that cortical thickening in the paracentral lobule correlated with higher sensitivity to cool stimulation, and an analogous cortical thickening in the right paracentral lobule was observed in individuals with chronic low back pain 30. Studies using transcutaneous electrical nerve stimulation reported that significant pain-related activation occurred in the S1, S2 regions and paracentral lobule 31.…”

Altered low-frequency oscillation amplitude of resting state-fMRI in patients with discogenic low-back and leg pain

“…In previous studies, similar atrophy and hypoactivity in sensory information transmission and processing regions were demonstrated in patients with chronic pain. 6 – 8 , 12 , 45 In discogenic LBLP patients, injuries to the surrounding nerves might affect or prevent the function/movement of the related regions, causing a decrease in the gray matter in the corresponding somatosensory regions. In contrast to other nonspecific low-back pain, discogenic LBLP might be attributable to a recognizable specific pathology associated with central vulnerability and/or sensitivity to pain.…”

“…Structural and functional alterations related to low-back pain or chronic back pain have been demonstrated using advanced neuroimaging techniques. Examples of these alterations include neuron metabolite abnormities; 5 cortical atrophy in the so-called “pain matrix”, including the S1/S2 regions, insula, and medial prefrontal cortex (mPFC); 6 , 7 cortical thinning in the “pain matrix” and pain-processing regions (trending in S1); 8 white matter microstructure damage in the corpus callosum and internal capsule; 9 – 11 hyper-activation in the mPFC after thermal stimulation 11 and activity in pain-associated regions (thalamus and cingulate cortex) following mechanical stimulation; 12 and highly consistent functional connectivity reorganization in several regions 11 , 13 – 17 with the exception of disrupted default mode network (DMN) connectivity. 14 – 16 , 18 …”

Structural Brain Imaging in People With Low Back Pain

“…Although the broader pain literature generally suggests a correlation between clinical outcome measures and brain volume(31, 56, 57), studies specifically examining LBP reported no correlations between such outcomes and brain volume even in the presence of brain volume differences(36, 40). Such findings question the clinical relevance of the differences in brain volume reported in previous studies.…”

“…Smaller brain volumes have been reported in such neurodegenerative diseases as multiple sclerosis(21–23), Alzheimer’s disease(24–26), and schizophrenia(27–29), and also in chronic pain conditions like fibromyalgia(30–32), complex regional-pain syndrome (33, 34), and chronic LBP(35, 36). To date, only a few structural brain imaging studies in people with chronic LBP(35–42) have been completed.…”