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Comparative Study
. 2011 May 18;31(20):7540-50.
doi: 10.1523/JNEUROSCI.5280-10.2011.

Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function

David A Seminowicz  1 , Timothy H Wideman, Lina Naso, Zeinab Hatami-Khoroushahi, Summaya Fallatah, Mark A Ware, Peter Jarzem, M Catherine Bushnell, Yoram Shir, Jean A Ouellet, Laura S Stone
Affiliations
Comparative Study

Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function

David A Seminowicz et al. J Neurosci. .

Abstract

Chronic pain is associated with reduced brain gray matter and impaired cognitive ability. In this longitudinal study, we assessed whether neuroanatomical and functional abnormalities were reversible and dependent on treatment outcomes. We acquired MRI scans from chronic low back pain (CLBP) patients before (n = 18) and 6 months after (spine surgery or facet joint injections; n = 14) treatment. In addition, we scanned 16 healthy controls, 10 of which returned 6 months after the first visit. We performed cortical thickness analysis on structural MRI scans, and subjects performed a cognitive task during the functional MRI. We compared patients and controls, as well as patients before versus after treatment. After treatment, patients had increased cortical thickness in the left dorsolateral prefrontal cortex (DLPFC), which was thinner before treatment compared with controls. Increased DLPFC thickness correlated with the reduction of both pain and physical disability. Additionally, increased thickness in primary motor cortex was associated specifically with reduced physical disability, and right anterior insula was associated specifically with reduced pain. Left DLPFC activity during an attention-demanding cognitive task was abnormal before treatment, but normalized following treatment. These data indicate that functional and structural brain abnormalities-specifically in the left DLPFC-are reversible, suggesting that treating chronic pain can restore normal brain function in humans.

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Figures

Figure 1.
Figure 1.
Cortical thickness in CLBP patients (n = 18) compared with controls (n = 16). Top row, Uncorrected t-value maps. Positive t values (red/yellow) represent areas of thinner cortex in CLBP patients than controls. Bottom row, Random-field theory-based cluster-corrected p < 0.05 maps. Blue areas represent clusters that are significantly thinner in CLBP patients than controls. Arrows point to significant peaks listed in Table 2. Scale bar shows t values. MTL, Medial temporal lobe; VLPFC, ventrolateral prefrontal cortex.
Figure 2.
Figure 2.
Cortical thickness changes in patients after treatment. A, t-value maps comparing cortical thickness after treatment compared with controls. Positive t values (red/yellow) represent thinner cortex in CLBP patients. B, p-value maps, cluster-corrected p < 0.05, corresponding to A. Note that the left DLPFC (arrow) is no longer significantly different between groups, as it was before treatment. C, Cortical thickness values for CLBP patients and controls before and after treatment for the significant peaks shown in Figure 1 and Table 2. Note that only the left DLPFC showed an increase in cortical thickness after versus before treatment. **p < 0.01, ***p< 0.001, compared to controls; ##p < 0.001, paired t test (n = 14) CLBP before versus after treatment. D, t- and p-value maps for patients who responded to treatment (n = 11) showing that the left DLPFC became thicker in patients after treatment compared with before treatment (arrow). E, Differences in DLPFC thickness for controls and patients 6 weeks (6 w) and 6 months (6 m) after treatment. At 6 months, data are shown for all patients (hatched red bar) as well as limited to those who responded to treatment (solid red bar). **p < 0.01, ***p < 0.001, one-sample t test, before treatment, CLBP versus controls. F, Pretreatment versus posttreatment line plots for each patient. Note that the majority of individuals showed an upward trend. MTL, Medial temporal lobe; VLPFC, ventrolateral prefrontal cortex.
Figure 3.
Figure 3.
Relationship between changes in pain, disability, and cortical thickness before versus after treatment. Left, Uncorrected t-value maps for the whole-brain correlations between pretreatment versus posttreatment cortical thickness and pain (SFMPQ, top panel) or pain-related disability (ODI, bottom panel). For these analyses, the search was limited to regions that were statistically different in controls compared with patients before treatment. Right, Scatterplots depicting the relationship between changes in cortical thickness and pain (SFMPQ, top panel) or disability (ODI, bottom panel) are shown for each significant peak. The analyses and plots include all 14 patients; p values on the plots are based on one-tailed t tests.
Figure 4.
Figure 4.
MSIT activations in CLBP patients and controls. A, Task-related activations in patients (blue) and controls (red). Areas of overlap are shown in pink. Note greater area of activation in patients. B, Task-related deactivations in patients (green) and controls (red). Areas of overlap are shown in yellow. Arrow, Deactivation of the DLPFC is observed in controls but not patients. C, Contrast maps of patients > controls (red) and controls > patients (blue) at a very liberal threshold (p < 0.05), illustrating that overall patients have far more widespread relative activation than controls. D, Average total number of voxels activated (t > 2) or deactivated (t < −2) in patients (LBP) and controls (CTR). Note the trend for more activated and fewer deactivated voxels in patients compared with controls. E, Relative increased activation in the left DLPFC (arrow) in patients before treatment compared with controls. F, Activity in the left DLPFC region shown in E, for patients and controls before and after treatment, where patients return toward normal activity levels. ##p < 0.001, one-sample t test, before treatment, CLBP versus controls; *p < 0.05, paired t test (n = 14) CLBP before versus after treatment. All brain images are t maps with threshold uncorrected p < 0.001 for visualization. See Table 3 and text for full statistics.
Figure 5.
Figure 5.
MSIT activation differences in CLBP patients before and after treatment. A, Patients had relatively more activity in only one area in the brain (p < 0.001 uncorrected), the left DLPFC, before treatment. Activity in this region normalized following treatment (plot). B, Line plots showing individual changes in DLPFC activity before versus 6 months after treatment. Note that almost all patients had a stronger deactivation after treatment. *p < 0.05, one-sample t test, before treatment, CLBP versus controls; ##p < 0.01, ###p < 0.001, paired t test (n = 14) CLBP before versus after treatment; 6 w, 6 weeks after treatment, 6 m, 6 months after treatment.
See this image and copyright information in PMC

References

    1. Ad-Dab'bagh Y, Lyttelton O, Muehlboeck JS, Lepage C, Einarson D, Mok K, Ivanov O, Vincent RD, Lerch J, Fombonne E, Evans AC. The CIVET image-processing environment: a fully automated comprehensive pipeline for anatomical neuroimaging research. Paper presented at the 12th Annual Meeting of the Organization for Human Brain Mapping; Florence, Italy; June. 2006.
    1. Apkarian AV, Sosa Y, Krauss BR, Thomas PS, Fredrickson BE, Levy RE, Harden RN, Chialvo DR. Chronic pain patients are impaired on an emotional decision-making task. Pain. 2004a;108:129–136. - PubMed
    1. Apkarian AV, Sosa Y, Sonty S, Levy RM, Harden RN, Parrish TB, Gitelman DR. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004b;24:10410–10415. - PMC - PubMed
    1. Avery DH, Holtzheimer PE, 3rd, Fawaz W, Russo J, Neumaier J, Dunner DL, Haynor DR, Claypoole KH, Wajdik C, Roy-Byrne P. Transcranial magnetic stimulation reduces pain in patients with major depression: a sham-controlled study. J Nerv Ment Dis. 2007;195:378–381. - PubMed
    1. Baliki MN, Geha PY, Apkarian AV, Chialvo DR. Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics. J Neurosci. 2008;28:1398–1403. - PMC - PubMed

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