neuroanatomical and functional abnormalities were reversible and dependent on treatment outcomes. We acquired MRI scans from
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
Chronic low back pain (CLBP) is the most prevalent form of
chronic pain, and it is the most common reason for disability in
the working-age population (Rapoport et al., 2004). CLBP has
been associated with abnormal brain anatomy and function.
When compared with pain-free controls, individuals with CLBP
bilateral dorsolateral prefrontal cortex (DLPFC), thalamus,
rietal cortex (Apkarian et al., 2004b; Schmidt-Wilcke et al., 2006;
Buckalew et al., 2008). In addition to CLBP, cortical abnormali-
as chronic headache, arthritis, and fibromyalgia (for review, see
function in people with CLBP (Giesecke et al., 2004; Baliki et al.,
2010). Evidence from pain neuroimaging and transcranial mag-
netic stimulation studies has linked the DLPFC to pain modula-
placebo analgesia (Wager et al., 2004; Krummenacher et al.,
2010), perceived control of pain (Pariente et al., 2005; Wiech et
al., 2006), and pain catastrophizing (Seminowicz and Davis,
There is evidence that some people with chronic pain also
have cognitive impairment (Kewman et al., 1991; Eccleston,
Apkarian et al., 2004a; Harman and Ruyak, 2005; Veldhuijzen et
individuals suggested that this cognitive impairment could be a
cognitive load-related activity was enhanced by pain, and even
vis, 2007b). In that study, acute noxious stimuli were adminis-
tered while healthy subjects performed a task. Here, instead of
pain would alter brain activity during cognitive performance.
This work was supported by an Early Career Award from the International Association for the Study of Pain
Investigator Award jointly funded by the CIHR, AstraZeneca, Canadian Pain Society Award XCP-83755 (L.S.S.);
Boursedechercheur-boursier“Junior2”Award14312fromtheFondsdelarechercheensante ´duQue ´bec(L.S.S.),
theLouiseandAlanEdwardsFoundation(L.S.S.,D.A.S.,Y.S.,M.A.W.),theInstitutderechercheRobert-Sauve ´ en
sante ´ et en securite ´ du Travail (T.H.W.), and the Physiotherapy Foundation of Canada (T.H.W.). We thank Sylvie
Correspondence should be addressed to Dr. Laura S. Stone, McGill University, Faculty of Dentistry, Alan
Edwards Centre for Research on Pain, 740 Penfield Avenue, Suite 3200, Montreal, QC H3A 1A9, Canada.
7540 • TheJournalofNeuroscience,May18,2011 • 31(20):7540–7550
Thus, we hypothesized that chronic pain would be associated
activated during an attention-demanding task.
We performed a longitudinal anatomical and functional MRI
study with CLBP patients and healthy controls to (1) identify
structural and functional differences between controls and pa-
tients before treatment, (2) determine whether these differences
were reversed following treatment, and (3) establish whether
these changes were linked to the amount of treatment-related
reduction of pain and disability.
Participants and study design. Eighteen patients (for sample descriptive
statistics, see Table 1 and supplemental Table S1, available at www.
jneurosci.org as supplemental material) with CLBP of intensity at least 4
of 10 for at least 1 year participated before treatment and 6 months
following treatment (n ? 14 for 6 month posttreatment group). Low
back pain patients were recruited sequentially in an outpatient orthope-
dic spine clinic or multidisciplinary pain center. Exclusion criteria in-
cluded pain duration of less than 1 year; pain intensity less than 4 of 10,
other chronic pain condition, neurological or psychological disorder,
other major illness such as cancer, inability to undergo MRI, pregnancy,
normal pharmacological treatment for pain (for details, see supplemen-
tal material, available at www.jneurosci.org). Sixteen healthy, pain-free,
returned 6 months following the first visit. As well, four controls and six
patients returned at 6 weeks after treatment. At each study session, sub-
jects were given questionnaires to assess pain and pain-related disability
and underwent MRI. The CLBP intervention was either spine surgery (8
block (6 of the patients in the posttreatment group) as per physician
recommendations (for details on diagnosis and treatment, see supple-
mental Table S2, available at www.jneurosci.org as supplemental mate-
factors were excluded. See Table 1, supplemental Tables S1, S2, and S3
the McGill University Faculty of Medicine Institutional Review Board,
and the McGill University Health Centre Research Ethics Office.
Questionnaires. Pain was assessed using the Short-Form McGill Pain
Questionnaire (SFMPQ) in which subjects rated the intensity of pain de-
scriptors (e.g., “stabbing”) on a scale from 0 (none) to 3 (severe) (Melzack,
1987) (for information on numerical rating scale data, see supplemental
material, available at www.jneurosci.org). Pain-related disability was deter-
mined using the Oswestry Disability Index (ODI) in which subjects rated
statements that best describe how pain affects different aspects of life (e.g.,
MRI. MRI scans were acquired on a 3T Siemens TIM Trio scanner
equipped with an eight-channel head coil. An anatomical scan was ac-
quired at the beginning of the session and lasted 5 min. The following
parameters were used: echo time (TE) 3 ms, repetition time (TR) 2.3 s,
flip angle 9°, resolution 1 ? 1 ? 1 mm. During a functional scan of ?5
min, subjects performed the Multi-Source Interference Task (MSIT) as
(2003). The task stimuli were presented on a screen in the subjects’ view
the amount of cognitive interference. In the most difficult level of the
task, the target character is a number displayed with other numbers of
varying size. This difficult task was contrasted with the motor control
task, in which an asterisk moved across the three positions in sequential
order. The parameters for the functional scan were as follows: echo-
planar imaging, TE 3 ms, TR 2.26 s, flip angle 90°, 128 frames, 64 ? 64
matrix, 38 slices for whole-brain coverage, resolution 4 ? 4 ? 4 mm.
Images were acquired in the axial plane, plus 30° from the anterior com-
missure–posterior commissure line to avoid the eyes.
Analysis. For preprocessing of cortical thickness, we used the CIVET
brief, the steps included nonuniformity correction to correct for field
inhomogeneity (Sled et al., 1998), normalization (nonlinear and lin-
ear steps) to the MNI/ICBM 152 template (Collins et al., 1994, 1995),
tissue classification [labeling each voxel as gray matter (GM), white
matter (WM), or CSF], and partial volume estimation (Tohka et al.,
2004), which labels voxels as partially GM, WM, and/or CSF (e.g., a
voxel covering the pial boundary could be labeled 50% GM, 50%
CSF). A cortical-fitting stage registers the brain surfaces to a model
that calculates 81,924 vertices, which are then back-transformed to
the original brains to calculate thickness in millimeters at each vertex
for each brain (MacDonald et al., 2000; Kabani et al., 2001; Kim et al.,
2007), followed by applying a diffusion-smoothing kernel of 30 mm
(Chung et al., 2003).
tical thickness analysis. For comparisons between controls and patients,
we applied a general linear model (GLM) comparing groups, with age as
a covariate of no interest. We performed separate GLMs for controls
versus patients before treatment and controls versus patients after treat-
ment. We also ran a mixed-effects (repeated-measures) model to exam-
ine patients before versus after treatment, with subject as the random
(within-subject) effect and time (before or after treatment) as the fixed
effect. This analysis included the 11 patients who responded to treat-
ment, which was defined as a reduction in score on either the ODI or
multiple comparisons across the whole brain were performed using ran-
dom field theory-based cluster analysis (Worsley et al., 1996). For the
analysis of patients before versus after treatment, we set a threshold so
in the cluster analysis. This strict correction for multiple comparisons is
Sex Age(baseline) Painduration(years)
Seminowiczetal.•ReversalofChronicPain-RelatedBrainChangesJ.Neurosci.,May18,2011 • 31(20):7540–7550 • 7541
anatomy (Apkarian et al., 2004b; Schmidt-Wilcke et al., 2006; Buckalew
et al., 2008). In analyses where we controlled for depression, we used
the POMS Depression–Dejection subscale scores as a covariate of no
fil.ion.ucl.ac.uk/spm/). Preprocessing involved realignment, normaliza-
tion, and smoothing at 8 mm FWHM. Analysis involved a mixed-effects
ditions and motion parameters as regressors in a GLM (first-level analy-
sis). In the second-level analyses, we used the results images from each
(for patients before vs after treatment). We used age as a covariate of no
interest in the two-sample t tests.
applied a threshold of FWE-corrected p ? 0.05 at the peak level for all
subjects at the initial time point (n ? 34). Because we had a specific
hypothesis about the left DLPFC in the group comparisons and in the
pre–post comparisons, we used an uncorrectedp ? 0.001 for these anal-
yses, and we report all results from these analyses. For peaks in the left
DLPFC, we used a small-volume correction of a 10-mm-radius sphere
around the peak of the total sample peak DLPFC deactivation (?24, 32,
42). A binary mask was created from the contrast of patients before
treatment minus controls at p ? 0.001, and this mask was used in the
search for voxels that correlated with change in SFMPQ and ODI to
match the method used for cortical thickness. We used the change in
SFMPQ and ODI scores separately, where the dependent data were the
subtraction of an individual’s pretreatment contrast image from the
posttreatment image. We applied a threshold of t ? 3 for this analysis.
To determine the total number of voxels activated and deactivated
during task, we calculated the number of voxels above a threshold of 2
from the SPM t maps for each individual on the MSIT difficult versus
motor control contrast.
task minus the ? for tapping control) were extracted for each subject.
We used PASW (Version 18.0, SPSS) for ANOVA comparing total
GM, CSF, and WM between controls and patients; SFMPQ, ODI, and
POMS scores before and after treatment; MSIT performance; voxel acti-
vation during the MSIT; and the correlations and partial correlations
presented in Results. Graphs were prepared in GraphPad Prism 4.0.
Relative to controls, patients before treatment had significantly
thinner cortex in left DLPFC, bilateral anterior insula/frontal
lobe, and right anterior cingulate cortex (ACC) (Fig. 1, Table 2).
and CSF) had no effect on the cluster analysis results. We found
(F(1,31)? 2.457, p ? 0.127), or WM (F(1,31)? 0.072, p ? 0.791).
Compared with controls, patients following treatment still had
thinner cortex in all the same clusters except the left DLPFC,
which no longer showed a significant difference between groups
(Fig. 2, Table 2). Nowhere in the brain did patients have thicker
cortex than controls.
would depend on treatment outcome, we identified 11 of the 14
8.30, p ? 0.05, 44% reduction] and/or pain-related disability
[ODI; pre/post ? 47.5 (4.89)/22.0 (5.45), F(1,10)? 17.2, p ?
0.005, 46% reduction] after treatment. The remaining three pa-
tients reported worse outcomes on either the SFMPQ or ODI,
and were classified as nonresponders [SFMPQ: pre/post ? 13.0
(5.69)/17.3 (2.03); ODI: pre/post ? 37.3 (10.5)/39.3 (13.5)]. In-
dividuals’ scores on SFMPQ, ODI, and POMS Depression–De-
jection subscale are shown in Table 1 and supplemental Table S1
(available at www.jneurosci.org as supplemental material).
After strict correction for multiple comparisons across the
brain, only one region—the left DLPFC (middle frontal gyrus,
Brodmann area 9, peak coordinate in MNI standard space ?45,
33, 24, t ? 7.70, p ? 0.00001)—had a significant increase in
cortical thickness (Fig. 2D,E) in responders. On an individual
basis, increases in cortical thickness were observed in every sub-
7542 • J.Neurosci.,May18,2011 • 31(20):7540–7550Seminowiczetal.•ReversalofChronicPain-RelatedBrainChanges
ject who responded to treatment. This is in contrast to decreases
of the three nonresponders. Figure 2F shows pretreatment and
posttreatment thickness for all patients in the sample. When all
14 patients were included in a repeated-measures analysis com-
paring before versus after treatment, there were no significant
differences in cortical thickness after correction for multiple
comparisons. These data indicate that the left DLPFC is abnor-
mally thin in untreated CLBP, and that effective treatment—in
to increased thickness in this area.
In responders, depression scores decreased from 8.81 (SEM ?
(F(1,10)? 15.5, p ? 0.005). We controlled for depression in the
analyses comparing patients with controls, as well as before
versus after treatment within patients. After controlling for
depression, the difference between controls and patients be-
fore treatment was slightly reduced, but the left DLPFC cluster
was still significantly thinner in patients than controls ( p ?
0.00005 vs p ? 0.0005). Similarly, the DLPFC was still signifi-
cantly thicker after than before treatment after controlling for
depression ( p ? 0.005 vs p ? 0.001). In contrast, the medial
prefrontal cortex/anterior cingulate cortex cluster (MPFC/ACC)
was no longer significantly thinner in patients before treatment
than controls after controlling for depression ( p ? 0.005 vs p ?
We examined the relationship between treatment-related
of areas that were shown to be thinner before treatment in pa-
tients compared with controls (the blue areas in Fig. 1). Specifi-
cally, we searched for regions where the change in thickness
from before to after treatment correlated with the magnitude of
treatment-related changes in SFMPQ or ODI scores. For both
SFMPQ and ODI, peak values were identified in the left DLPFC
(for ODI, coordinates were ?43, 18, 30, t ? 3.33; for SFMPQ,
same peak for ODI, t ? 2.68, and SFMPQ, t ? 3.50), where
recovery of cortical thickness was significantly correlated with
reduced pain intensity and improvement in physical disability.
Because change in SFMPQ and change in ODI were highly cor-
similar areas were related to these measures. However, improve-
ment in physical disability also correlated with posttreatment
after controlling for ODI (r ? 0.59, p ? 0.05) (Fig. 3). Note that
all patients were included in these analyses.
Reaction times on the difficult task did not differ significantly
between controls and patients before treatment (F(1,33)? 1.18,
2.96, p ? 0.1). Performance of the difficult task compared with
the tapping-only condition led to activations in regions of the
task-positive network and deactivations in the task-negative net-
work as described by Fox et al. (2005). Although the task-related
activations and deactivations were similar for each group, we
noticed qualitatively that patients had overall more activations
and fewer deactivations. In Figure 4A, patients (blue) had a
greater area of task-related activations than controls (red); areas
of overlap are shown in pink. In Figure 4B, patients (green) had
fewer task-related deactivations than controls (red); areas of
overlap are shown in yellow. In Figure 4C, we show a contrast
x,y,z(MNIcoordinates) Peaktvalue NumberofverticesinclusterFWE-correctedpvalueforcluster
L 449 0.0053
Seminowiczetal.•ReversalofChronicPain-RelatedBrainChanges J.Neurosci.,May18,2011 • 31(20):7540–7550 • 7543
map of patients ? controls (red) and controls ? patients (blue)
at a very liberal threshold ( p ? 0.05) to illustrate that, overall,
patients have far more widespread relative activation than con-
(deactivations) and above 2 (activations) and plotted these aver-
age values (Fig. 4D). For the pretreatment time point, the mean
number of voxels activated (SEM) was 36,963 (6574) in controls
versus 52,380 (6180) in patients (F(1,33)? 1.58, p ? 0.1), and the
number of voxels deactivated was 19,276 (5704) in controls ver-
sus 12,782 (3200) in patients (F(1,33)? 1.04, p ? 0.1).
Patients (n ? 18) before treatment had relatively more task-
4E). The plot in Figure 4F shows that patients did not deactivate
this area as strongly as controls. Following treatment, activity in
patients (n ? 14) in only one region—the left DLPFC—was de-
activated relative to before treatment (paired t test; ?28, 24, 44,
t ? 4.36, p ? 0.05 small-volume corrected) (Table 3, Fig. 5).
Thus, following treatment, pain-related abnormalities in the left
DLPFC returned toward control values. There were no areas
where controls had relatively more activation than patients be-
activated in patients after versus before treatment. Controlling
ison did not reduce the significance of the DLPFC change (?30,
significant change in task performance after treatment, and the
times did not correlate with the change in DLPFC activity (r ?
0.16, p ? 0.5), suggesting that the change in left DLPFC was not
simply related to improved task performance.
Unlike our data demonstrating an association between in-
creasing cortical thickness and treatment outcomes, there was
no correlation between the extent of reduced pain or pain-
related disability (SFMPQ and ODI scores, respectively) and
the amount of reduction in left DLPFC activity during the
cognitive task after versus before treatment. Furthermore, the
pretreatment to posttreatment changes in left DLPFC thick-
ness and left DLPFC deactivation were not correlated in all
7544 • J.Neurosci.,May18,2011 • 31(20):7540–7550 Seminowiczetal.•ReversalofChronicPain-RelatedBrainChanges
patients (r ? 0.103, p ? 0.72, n ? 14) or in responders only
(r ? 0.214, p ? 0.53, n ? 11).
A small subset of the subjects (4 controls and 6 patients) also
before treatment and 6 months after treatment. Although we
considered the groups too small for statistical comparison, the
plots in Figures 2E and 5A and in supplemental Figure S1 (avail-
able at www.jneurosci.org as supplemental material) illustrate
the contrast between the lack of change in cortical thickness at 6
weeks compared with the large change in functional activity at
that same time point. We also have included plots of individuals’
vs after treatment) in supplemental Figure S1 (available at www.
jneurosci.org as supplemental material). For the functional data,
at 6 weeks the activity level is intermediate to the pretreatment
and 6 month posttreatment time points, whereas for cortical
thickness, the 6 week data do not seem to be related to the 6
month change. This result suggests that the functional change
occurs early, whereas more time is needed for the structural
Our findings provide strong evidence that pain-related neuro-
anatomical and functional changes are reversible with effective
treatment. Furthermore, we have provided evidence for a link
between regional brain function and anatomy. The left DLPFC
was thinner and was activated abnormally in patients before
treatment relative to controls; after treatment, the same region
a cognitive task. Previous research has shown altered brain anat-
Wilcke et al., 2005, 2006; Kuchinad et al., 2007; Buckalew et al.,
Teutsch et al., 2008; Hsu et al., 2009; Obermann et al., 2009;
Rodriguez-Raecke et al., 2009; Wood et al., 2009; Gwilym et al.,
2010; Seminowicz et al., 2010; Tu et al., 2010), and other studies
have linked cortical thickness to cognitive function (Hadjikhani
et al., 2007; Dickerson et al., 2008; Sowell et al., 2008). To our
knowledge, no other study has shown a link between gray matter
density or cortical thickness loss and altered cognitive task-
related brain activity in chronic pain.
Recent studies suggest that changes in brain gray matter can oc-
cur when pain is eliminated (Obermann et al., 2009; Rodriguez-
Raecke et al., 2009; Gwilym et al., 2010). The current study
quantitative measure that can be compared between studies, un-
like gray matter density. Furthermore, we demonstrate that the
left DLPFC got thicker in each CLBP patient who improved after
pended on the amount of improvement in clinical outcome
measures in each patient. The patients in our sample received
treatment interventions that targeted the presumed pain genera-
tors within the musculoskeletal system (i.e., spinal structures).
The mechanisms by which these interventions result in changes
in the DLPFC are currently unclear. A recent longitudinal study
in rats reported that ongoing chronic pain resulted in reduced
gray matter in the prefrontal cortex that was temporally corre-
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
Relationship between changes in pain, disability, and cortical thickness before versus after treatment. Left, Uncorrected t-value maps for the whole-brain correlations between
Seminowiczetal.•ReversalofChronicPain-RelatedBrainChanges J.Neurosci.,May18,2011 • 31(20):7540–7550 • 7545
et al., 2009). Thus, it seems that the development of chronic pain
can lead to prefrontal cortical thinning, and—from the present
results—that reducing pain can lead to prefrontal cortical thick-
ening. It is also evident that anxiety and depression are closely
and the present study, affective measures alone did not explain
the differences in cortical volume or thickness. The reduction of
incoming nociceptive inputs from peripheral structures likely
accounts for part of the improvement in pain and pain-related
disability. It will be important for future studies to determine
whether interventions specifically targeting psychosocial
rather than biomechanical components of chronic pain (e.g.,
cognitive–behavioral therapy) result in similar recovery in
We show here that the increase in cortical thickness following
both the left DLPFC and S2/posterior insula (pINS) was related
to general improvement after treatment (both pain and pain-
recovery of M1, and pain was specifically related to recovery of
right aINS. This is consistent with both the role of M1 in motor
the estimation of pain magnitude (Baliki et al., 2009).
The outcomes for our patient sample, in which almost every
patient experienced a reduction in pain, were generally better
than previously reported (Cohen and Raja, 2007; Chou et al.,
in more conservative estimates of treatment success. Further-
more, our follow-up evaluation was only 6 months after inter-
vention. It is possible that our “responders” may go on to
time points. Future studies should build on our findings by
exploring similar outcomes over a longer follow-up period,
and by using patients who do not respond to treatment as a
Because chronic pain and depression commonly co-occur
(Krishnan et al., 1985) and because the DLPFC has been impli-
7546 • J.Neurosci.,May18,2011 • 31(20):7540–7550 Seminowiczetal.•ReversalofChronicPain-RelatedBrainChanges
2007), we controlled for levels of depression in our study using
the score on the POMS Depression–Dejection subscale. Al-
though depression is an important factor in CLBP and may ex-
and controls, in the present study, it did not explain the increase
in DLPFC thickness following treatment in our sample. An in-
teresting finding was that the MPFC/ACC cluster that was thin-
ner in patients before treatment than controls was no longer
significantly thinner after controlling for depression. The ACC
has aberrant activity in major depression (Mayberg, 2009) and is
implicated in the affective aspect of pain (Kulkarni et al., 2005;
Vogt, 2005). Note that the midcingulate cortex, which is usually
activated by acute noxious stimuli and is probably related to ac-
tion selection (Kulkarni et al., 2005; Vogt,
2005; Oshiro et al., 2009), did not show a
difference between patients and controls
in the present study.
During performance of a cognitively de-
manding task, the activation patterns in
patients and controls were generally sim-
ilar. However, patients activated the cog-
nitive network to a greater extent and had
relatively fewer deactivations than con-
it was in the controls. That patients had
relatively fewer deactivations is consistent
with the results of Baliki et al. (2008),
where CLBP patients had relatively fewer
deactivations during a simple task. Although the precise role of
with previous literature showing that pain is associated with in-
vis, 2007b). After treatment, patients had normal task-related
activity in this area, and the left DLPFC was the only area that
showed a difference in activity in patients after versus before
treatment, just as the left DLPFC was the only area that got
thicker in patients. This strongly indicates that the change in
brain structure (increase in cortical thickness in the left DLPFC)
is related to function.
treatment were consistent across subjects. Regions that had dif-
Seminowiczetal.•ReversalofChronicPain-RelatedBrainChangesJ.Neurosci.,May18,2011 • 31(20):7540–7550 • 7547
ferences in cortical thickness or cognitive task-related activity in
each patient before versus after treatment were identified by
repeated-measures analyses. In both cases, the left DLPFC was
identified. The pretreatment and posttreatment cortical thick-
ness and task-related activity values in this region are shown for
measures, the majority of patients show both (1) increased cor-
tical thickness after treatment (Fig. 2F) and (2) increased deacti-
DLPFC were highly consistent across individuals.
Several important problems remain for future research to re-
solve. First, are the findings here specific to CLBP, or are they
other chronic diseases such as posttraumatic stress disorder,
loss in chronic pain is a consistent finding, the brain areas af-
fected in each sample or pain condition are variable (May, 2008;
the currently reported treatment-related changes are relevant to
to what aspect of the treatment were the changes in DLPFC re-
for low back pain. In this study, we focused our analysis on
changes in pain and pain-related disability, regardless of the
treatment or mechanism of action. It is quite possible that a
strong placebo effect, as is often seen in chronic pain (Seeley,
1990; Hoffman et al., 2005), contributed to the improved out-
comes observed in this study.
Another important question is as follows: Are the changes in
left DLPFC and elsewhere related to pain modulation? Several
studies have indicated a role for the prefrontal cortex in pain
et al., 2004; Wiech et al., 2006; Krummenacher et al., 2010). If
recovery of DLPFC thickness and/or function is necessary for
it has already shown some promise in studies of short- and long-
term analgesia from repetitive transcranial magnetic stimulation
(rTMS) of the prefrontal cortex (Reid and Pridmore, 2001;
Brighina et al., 2004; Graff-Guerrero et al., 2005; Avery et al.,
2007; Borckardt et al., 2007, 2008; Nahmias et al., 2009; Fierro et
in the present study. Finally, the increased cortical thickness in
S2/pINS that correlated with improvements in both pain and
inputs because this region has direct spinothalamic inputs. Fu-
ship between persistent peripheral input and S2/pINS thickness.
may vary by pain type (i.e., neuropathic vs non-neuropathic) (Ap-
karian et al., 2004b). In the current study, the experimental group
reported chronic axial low back pain, chronic radicular pain, or
both. Although this strategy did not allow for differentiation be-
tween nociceptive and neuropathic pain, the sample was represen-
tative of the mixed etiology of CLBP in the general population.
Furthermore, different treatment interventions (surgery or facet
joint block) were selected to maximize the likelihood of pain relief
for each individual patient as would be typical in a clinical setting.
Rather than attempting to differentiate between differences in pain
posttreatment improvement in pain and disability. Future studies
could be conducted to further dissect the impact of pain types and
In summary, we have shown that the left DLPFC, which was
patients before treatment compared with pain-free controls, be-
came significantly thicker and had normal activity following
on the extent of the patient’s improvement after treatment. Our
results imply that treating chronic pain can restore normal brain
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