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Psychobiological Correlates of Improved Mental Health in Patients With Musculoskeletal Pain After a Mindfulness-based Pain Management Program

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Objectives: Mindfulness-based pain management programs (MBPMs) aim to improve mental and physical health in individuals with chronic pain. In this study, we investigated whether improvement in mental health might require (1) reduction in the sensory pain experience and brain correlates of that experience, and/or (2) improved perceptions of the controllability of pain and corresponding brain activity related to cognitive control and emotional regulation. Methods: Twenty-eight patients with chronic pain were assessed and randomized into an intervention group (who attended an 8-wk MBPM) or a control group (treatment-as-usual), before being reassessed after 8 weeks. Outcome measures included clinical pain, perceived control over pain, mental and physical health, and mindfulness. Neural activity was measured during the anticipation and experience of acute experimental pain, using electroencephalography with source reconstruction. Results: Improvements were found in the MBPM group relative to the control group in mental health, which related to greater perceived control of pain, but not to reductions in clinical or experimental pain ratings. Anticipatory and pain-evoked event-related potentials to acute experimental pain were decreased, but sources of these event-related potentials were estimated to be in regions that modulate emotional responses rather than pain intensity. Mental health and perceived control outcomes correlated with reduced anticipatory deactivations of dorsolateral prefrontal and somatosensory cortices. Discussion: Increased activity in cognitive control regions of the brain during pain anticipation related to improved mental health and perceived control over pain, but not to decreased pain experience. Greater perceived control may therefore result from improved regulation of the emotional response to pain.
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Psychobiological Correlates of Improved Mental Health
in Patients With Musculoskeletal Pain After a
Mindfulness-based Pain Management Program
Christopher A. Brown, PhD and Anthony K. P. Jones, MD
Objectives: Mindfulness-based pain management programs (MBPMs)
aim to improve mental and physical health in individuals with chronic
pain. In this study, we investigated whether improvement in mental
health might require (1) reduction in the sensory pain experience and
brain correlates of that experience, and/or (2) improved perceptions of
the controllability of pain and corresponding brain activity related to
cognitive control and emotional regulation.
Methods: Twenty-eight patients with chronic pain were assessed
and randomized into an intervention group (who attended an 8-wk
MBPM) or a control group (treatment-as-usual), before being re-
assessed after 8 weeks. Outcome measures included clinical pain,
perceived control over pain, mental and physical health, and
mindfulness. Neural activity was measured during the anticipation
and experience of acute experimental pain, using electroencephalo-
graphy with source reconstruction.
Results: Improvements were found in the MBPM group relative
to the control group in mental health, which related to greater
perceived control of pain, but not to reductions in clinical or ex-
perimental pain ratings. Anticipatory and pain-evoked event-
related potentials to acute experimental pain were decreased, but
sources of these event-related potentials were estimated to be in
regions that modulate emotional responses rather than pain in-
tensity. Mental health and perceived control outcomes correlated
with reduced anticipatory deactivations of dorsolateral prefrontal
and somatosensory cortices.
Discussion: Increased activity in cognitive control regions of the
brain during pain anticipation related to improved mental health
and perceived control over pain, but not to decreased pain expe-
rience. Greater perceived control may therefore result from im-
proved regulation of the emotional response to pain.
Key Words: pain, anticipation, meditation, mindfulness, attention,
EEG, nociception
(Clin J Pain 2013;29:233–244)
Mindfulness-based interventions teach psychological
skills that can improve the quality of life of in-
dividuals with long-term conditions,1,2 including those with
chronic pain.3,4 However, significant effects on physical
symptoms such as pain are less commonly reported than
mental health and other quality-of-life outcomes.3–5 There
is no evidence that a reduction in physical symptoms is
needed before improvements in psychological functioning
can be observed. On the contrary, definitions of mindfulness
suggest that the aim is not to bring about particular desired
states or experiences, but rather to accept experiences as
they are without reacting to them or judging them neg-
atively.6It is therefore clear that the main aim of mindful-
ness programs for pain is not sensory pain reduction, but
rather better control over the cognitive and emotional as-
pects of pain, and it is this that defines the usefulness of
mindfulness within a pain self-management context.
To establish whether mindfulness-based interventions
achieve this goal, evidence is required that improvements in
mental health are not dependent on a reduction in the sen-
sation of pain, but rather relate to perceptions of the con-
trollability and manageability of the cognitive and emotional
components of pain. This is thought to depend on the ability
to attend to experiences in the present moment, and to
withdraw attention from ruminative thinking based on past
and future.6Psychometric scales exist that specifically measure
this aspect of mindfulness in a person,7which have been related
to positive coping in chronic pain populations.8However, it
has not been clearly demonstrated that the mental health
benefits of this training are related to improved perceptions of
control over the pain response rather than a reduction in
perceptions of pain sensations.
In the current study, we investigated the effects of a
mindfulness-based pain management program (MBPM) on
mental health, while also measuring changes in the perceived
level of control over pain, readiness to engage in a self-
management approach to pain, clinical pain symptoms, and
the attentional aspects of mindfulness as a potential mediator
of these effects. Perceived control was of particular interest
as a construct that has previously been related to pain proc-
essing and perception,9,10 mental health outcomes,11,12 and
coping ability.13
Research into mechanisms of psychotherapeutic action
should ideally include data across biological, cognitive, and
behavioral levels.14 Although psychometric outcome meas-
ures can be useful for understanding how interventions work,
a complementary approach is the use of brain imaging. Brain
imaging provides the ability to probe the biological effec-
tiveness of a psychological intervention, especially in terms of
whether sensory pain processing per se is affected, or whether
secondary (emotional and/or cognitive) processes are af-
fected. Better definition of the biological processes involved
Received for publication October 4, 2011; revised January 17, 2012;
accepted January 22, 2012.
From the Human Pain Research Group, University of Manchester,
Salford Royal NHS Foundation Trust, Salford, UK.
There are no financial or other relationships that might lead to a
conflict of interest in publishing this article. This work was funded
by the Mind and Life Institute (http://www.mindandlife.org/),
Arthritis Research UK (http://www.arthritisresearchuk.org/), and
the University of Manchester. The funders had no role in study
design, data collection and analysis, decision to publish, or pre-
paration of the manuscript.
Reprints: Christopher A. Brown, PhD, Human Pain Research Group,
University of Manchester, Clinical Sciences Building, Salford Royal
NHS Foundation Trust, Salford M6 8HD, UK (e-mail: christopher.
brown@manchester.ac.uk).
Supplemental Digital Content is available for this article. Direct URL
citations appear in the printed text and are provided in the HTML
and PDF versions of this article on the journal’s Website,
www.clinicalpain.com.
Copyright r2012 by Lippincott Williams & Wilkins
ORIGINAL ARTICLE
Clin J Pain Volume 29, Number 3, March 2013 www.clinicalpain.com |233
may, in the future, aid in better targeting treatments based
on consideration of the patients’ psychological and biological
profile. Human brain imaging data may be considered more
objective than psychometrics, but at the expense of being
more difficult to interpret, requiring reference to correlations
with psychometric and behavioral data.
Studies have shown that mindfulness training improves
executive brain functioning15–18 and affects associated neu-
ral processes.19,20 Increased dorsolateral prefrontal cortical
(DLPFC) activity, in particular, has been associated with
states of mindfulness meditation,19,21 cognitive and behav-
ioral control,22 emotional regulation,23 and perceived control
over pain.24 From this evidence, we hypothesized that
mindfulness training would be associated with increases in
DLPFC activity during anticipation of pain, when there is an
opportunity for emotional regulatory strategies to be exec-
utively used. We also hypothesized these changes would be
related to mental health and pain control/self-management
outcomes, rather than a reduction in pain. Such changes in
DLPFC might therefore reflect improvements in cognitive
and emotional responses to pain, rather than reductions in
pain itself.
To examine neural activity, we used a method pub-
lished previously25 in which we induced experimental laser
pain, rather than clinical pain. Owing to the brevity of the
laser stimuli, this enabled separate measurements of neural
activity relating to pain anticipation and pain experience
using electroencephalography (EEG), which would be
challenging to achieve by stimulating clinical pain. Our
previous work25 showed that long-term meditation experi-
ence (over years/decades) was associated with less perceived
unpleasantness of experimental pain, with concurrent re-
ductions in pain processing in the midcingulate cortex.
However, the study was a case-control design and relied on
correlations between reported meditation experience and
outcomes in a nonpatient group, which has clear limitations
as discussed elsewhere.26 Although the experimental meth-
ods used in the current study were almost identical to the
previous study, this study expands on that work by meas-
uring clinical outcomes and neural activity in a clinical pain
population, and comparing identical measurements before
and after a mindfulness intervention.
MATERIALS AND METHODS
Ethics Statement
The research study was approved by North Man-
chester Local Research Ethics Committee in the United
Kingdom. Written informed consent was obtained from
study participants.
Study Design
The study was a 22 factorial design with one factor
being group (an intervention group and a control group), and
the other factor being time (first and second experimental
sessions). There was a 2-week window, either side of the treat-
ment, during which we scheduled patients for experimental
visits. Because this depended on patient availability, there was
some variation between participants in how far apart the
2 experimental sessions were, and this varied between 8 and
12 weeks. Patients in the control group were scheduled for
their visits according to a comparable timeframe.
Between experimental sessions, the intervention group
participated in an MBPM, run by Breathworks Community
Interest Company, entitled Living Well with Pain and Illness.
The details of this intervention and some of the impact on
patients with chronic pain have been documented else-
where.27 The program consisted of a total of 20 hours of
training (2.5 h/wk for 8 wk). The program teaches not to try
to do anything about the underlying unpleasant sensation of
pain, but to train in mindfulness to lessen the reactive cycle
that leads to physical and emotional stress. This is done by
teaching breath awareness, body awareness, gentle move-
ment, training in how to manage pain, illness and fatigue in
daily life, and cultivating kindliness and compassion toward
oneself and others. The main components of the program
are:
1. Breath awareness: Investigating breathing habits, learn-
ing to use the natural breath as an aid to managing pain,
illness, or stress, developing habits of breathing into
difficult experiences to soften resistance to pain or illness
and to let go of tension.
2. The body scan: Developing greater awareness of the body
by “scanning” through the whole body with careful
attention, using the breath to help let go of areas of pain
and/or tension.
3. Mindful movement: Stopping the cycle of disuse, loss of
function and more pain or fatigue with some gentle
movements, based on yoga and pilates.
4. Mindfulness of daily life (pacing): Bringing awareness to
the activities of daily life to prevent overdoing on good
days and collapsing on bad days. This involves using
diaries and symptom scoring to become more aware of
what activities cause aggravation, and then to make
conscious choices toward a more balanced approach to life.
5. Three-minute breathing space: Taking 3-minute breaks in
the midst of activity to rest awareness with the breath.
6. Mindfulness of breathing: Focusing on the breath in
order to learn to reduce the activity of the mind, making
it easier to watch our thoughts, feelings, and sensations
come and go without judging them, identifying with
them or pushing them away.
7. Kindly awareness: Firstly spending time becoming aware
of the unpleasant and the pleasant aspects of experience in
the present moment. Then, broadening to include other
people and developing empathy by reflecting on what
is shared by all: the breath, pleasure, pain, and eventually,
the sickness and degeneration that comes with age.
Between the first and second sessions, control group
participants continued with treatment-as-usual, and were
given the option of participating in the mindfulness course
after completing the second session.
Participants
The recruitment of participants for the study was ad-
vertised as open to right-handed patients with any type of
musculoskeletal pain. Patients were excluded from the
study if their medical records showed a history of neuro-
logical, psychiatric, or cardiovascular disease. Our aim
was to recruit patients with “normal” levels of distress for
a chronic pain population, which would be elevated com-
pared with a healthy population, but to screen out major
psychiatric disorder that had been diagnosed by a specialist.
These included patients with major depression, bipolar
disorder, anxiety disorders (obsessive compulsive disorder,
panic, phobias, generalized anxiety disorder), and schizo-
phrenia. It was expected that many patients recruited would
be likely to have mild to moderate levels of anxiety and/or
depression that had not be diagnosed.
Brown and Jones Clin J Pain Volume 29, Number 3, March 2013
234 |www.clinicalpain.com r2012 Lippincott Williams & Wilkins
To power the study, our primary concern was to test
for neurobiological effects of the intervention, particularly
differences in anticipatory responses. We based the power
calculation on data obtained from a case-control study
published previously25 in which healthy volunteers with an
established meditation practice showed significant differ-
ences in the amplitude of the anticipatory-evoked potential
compared with those without meditation experience. The
mean amplitude of the response in the meditation group
was 1.09 and in the control group was 2.50, with SDs
of 1.17 and 1.94, respectively. This amounts to an effect size
of 0.89. At 80% power and an a-level of 0.05 in a 1-sided
test, this would require 17 participants per group to show
a statistically significant effect. We therefore aimed to re-
cruit 20 patients to each group in the present study to see
whether similar differences could be found comparing pre-
intervention and postintervention data. In the end, our
dropout rate caused this target to be missed (for details on
dropouts, see below).
Patients were screened as follows. A total of 1014 pa-
tients were screened using electronic medical notes. Five
patients were excluded on the basis of prior history of psy-
chiatric disorders. A total of 1009 patients were invited to
take part in the study. Of these, it was found that 91 did not
meet the inclusion criteria for reasons not detailed in their
medical notes (eg, many were left handed). A total of 343
patients declined to take part, whereas there was no response
from 535 patients. A total of 40 patients were recruited.
All 40 participants gave informed written consent.
Patients were randomized into 1 of 2 groups: an MBPM
group and a control group. Patients were allocated to 1 of
5 MBPM courses, according to their availability, that were
also open to self-referring participants not involved in the
study, with a maximum of 15 participants per course. Of the
original 40 patients, a total of 9 dropped out of the study,
5 from the control group and 4 from the intervention group.
Of the 4 who dropped out from the intervention group, one
did so after the initial experimental session but before the
pain management course, one did so after the first week of
the course, one after the second week of the course, and the
fourth after completing the course but before the second
experimental session. Unfortunately, we were not able to
establish the reason why all patients dropped out when they
did. We have documented reasons for 6 of the 9 dropouts.
The remaining patients did not provide details of their
reasons for discontinuing. Of the patients who gave reasons,
2 dropped out because they found the experimental pain
procedure too unpleasant to want to return a second time,
1 experienced family bereavement, 1 needed a medical op-
eration, 1 started a new job and it was not practical to
attend the treatment sessions, and 1 was diagnosed with
significant psychiatric comorbidities and recommended not
to continue with the study by a psychotherapist. Of the
remaining 31 patients, 3 were found to have poor-quality
EEG recordings, reducing the number to 28. In the end,
15 patient data sets were completed in the MBPM group,
and 13 in the control group.
The details of the 28 patients whose data were ana-
lyzed are as follows. The clinical diagnoses of all patients
are shown in Table 1, from which is it clear that most
patients (18/28) had been diagnosed with fibromyalgia. The
intervention group contained 8 patients with fibromyalgia
(2 with arthritic comorbidities) and the control group
contained 10 patients with fibromyalgia. The mean age of
patients in the intervention group was 48 ± 10, and in the
control group was 45 ± 12. Independent samples ttest
statistics revealed no significant difference between the ages
of the 2 groups. The intervention group was composed of
12 females and 3 males, whereas the control group con-
tained 9 females and 4 males.
Self-report Measures
Questionnaires were administered once during each
of the 2 experimental sessions, and were used to measure
improvements in mental and physical health, the controll-
ability and self-management of pain, sensory, and affective
appraisal of clinical pain, and mindfulness. Mental and
physical health outcome variables were measured using the
summary scores from the Short-Form 36 health survey.28
Improvements in the self-management of pain were as-
sessed using the Pain Stages of Change questionnaire,29
which is designed to measure the stages a patient goes
through in their readiness to adopt a self-management
approach to pain. This scale has been found to best fit a
2-factor structure: “Contemplation” of change and “Engage-
ment” in pain self-management, which yield separate scores
for each.30 The “Engagement” subscale summarizes patients’
level of acceptance of a self-management approach to
chronic pain, their attempts to improve self-management
skills, and continued development of those skills. We meas-
ured “perceived control over pain,” using the brief version of
the Survey of Pain Attitudes.31 This subscale contains items
that relate to the ability to control the actual sensation of
pain (eg, “There are many times when I can influence the
amount of pain I feel.”), but mostly within the context
of influencing pain indirectly through the ability to regulate
thoughts and emotions (e.g. “Just by concentrating or re-
laxing I can ‘take the edge’ off of my pain,” and “I believe
that I can control how much pain I feel by changing my
thoughts,” and “I have noticed that if I can change my
emotions I can influence my pain.”). The scale therefore
broadly relates to the management and regulation of pain as
a multidimensional (sensory, emotional, cognitive) experi-
ence, with a focus on cognitive and emotional responding.
We assessed clinical pain experience using the Short-Form
McGill Pain Questionnaire,32 which has subscales for sen-
sory and affective pain. Mindfulness was assessed using the
Mindful Attention and Awareness Scale (MAAS),7which
mostly measures the aspect of mindfulness related to present-
focused attention and acting with awareness.6
Neural Responses to Acute Pain
To measure treatment effects on pain processing, the
options are to either measure brain responses to chronic pain
TABLE 1. Numbers Recruited Into the Study According to
Diagnosis and Group
No. in Each Group
Diagnosis Intervention Control
Fibromyalgia 10 6
Rheumatoid arthritis 1 2
Cervical nerve root impingement 0 3
Osteoarthritis 1 0
Fibromyalgia + rheumatoid arthritis 0 1
Fibromyalgia + osteoarthritis 0 1
Psoriatic arthritis 1 0
Low back pain 1 0
Ankylosing spondylitis 1 0
Clin J Pain Volume 29, Number 3, March 2013 Brain Effects of Mindfulness in Chronic Pain
r2012 Lippincott Williams & Wilkins www.clinicalpain.com |235
or responses to acute experimental pain. Acute experimental
pain models are limited in understanding responses to
chronic pain, particularly because of the difference in mean-
ing attributed to the 2 types of pain. However, acute pain
models have the advantage of being able to use a highly
controllable stimulus that could be kept constant between
experimental sessions separated by time. The ability to ma-
nipulate chronic pain experimentally is very challenging and
likely to lead to much greater unwanted variability in the data
as a result of not being able to standardize the type, quality,
and intensity of pain across participants and across experi-
mental sessions. Although the use of acute pain also has
significant disadvantages, the advantages appear to outweigh
these, as an experiment based on experimental manipulation
of chronic pain would be even more difficult to conduct and
interpret. In this study, neural activity was therefore mea-
sured relating to anticipation and experience of acute pain.
During each experimental session, subjective reports and
electrophysiological responses to acute pain were assessed,
using a protocol published previously (see Brown and Jones25
for details). Briefly, acute pain was induced using a CO
2
laser
stimulus that specifically activates nociceptors in the skin.33
Heat stimuli of 150 ms duration and a beam diameter of
15 mm were applied to the dorsal surface of the participants’
right forearm. Patients were not instructed to use any medi-
tation techniques during the experiment, but were also not
explicitly told not to meditate.
In the first of the 2 sessions, an initial psychophysics
procedure was performed as detailed elsewhere25 to deter-
mine a moderately painful level of laser stimulus intensity
for each participant (level 7 on a 0 to 10 scale, in which 0
was equivalent to “not at all unpleasant,” and 10 was equi-
valent to “extremely unpleasant”). This intensity was used
for both sessions, and hence the laser energy did not vary
between sessions. The main experiment, also detailed in a
previous paper,25 consisted of the delivery of 30 moderately
painful laser pulses, each occurring after 3 visual antici-
pation cues (Fig. 1A). Participants were instructed to focus
on the unpleasantness of the pain at all times (during pain
anticipation and experience), to maximize the processing of
pain in emotion-related neural networks, although we have
no data to judge the extent to which this was achieved in
individual patients. It was explained to participants that
focusing on the unpleasantness of pain meant being aware
of any unpleasant sensations in the arm that might have
been there even in the absence of pain stimuli (eg, during
anticipation). In response to each laser pulse, participants
provided a rating of the unpleasantness using the same 0 to
10 numerical scale as used in the psychophysics testing
procedure as detailed above.
EEG Recordings of Anticipatory and Pain-evoked
Responses
We measured the brain’s evoked response to antici-
pating and experiencing pain, by taking EEG recordings
from 61 scalp electrodes placed according to an extended
10-20 system (EasyCap in combination with a Neuroscan
system). Bandpass filters were set at DC—100 Hz, with a
sampling rate of 500 Hz and gain of 500. A notch filter was
set to 50 Hz to reduce electrical interference. Electrodes were
referenced to the ipsilateral (right) earlobe, and recordings
were also taken from the contralateral (left) earlobe for off-
line conversion to linked-ears reference. The vertical and
horizontal electro-oculograms were measured for off-line
reduction of blink-and-eye-movement artifacts.
Analysis of Self-report Measures
There was a lack of normality in some of the self-report
measures (McGill pain scores, MAAS scale) after splitting
the data into groups and sessions. We found what appeared
to be significant amounts of kurtosis in the McGill pain
scores, caused by the presence of outliers (3 in total). The
MAAS scale also had 1 outlier, but only in the control group
pretreatment scores. Taking this into account as well as
the relatively small sample size, we considered that non-
parametric tests would result in more robust statistics, and
that this was appropriate to apply to all the outcome meas-
ures. Initial analyses used nonparametric statistics with
1-tailed tests (hypothesizing a direction of change toward
improvement in the MBPM group). Nonparametric repeated-
measures ANOVAs were conducted (following the method of
Brunner and Puri34) on each relevant subscale from each self-
report measure, with group (intervention, control) and session
(first, second) as factors. Main effects and interactions are
reported for a total of 8 outcome measures. Results were
considered significant after correcting the P-values using the
false discovery rate (FDR) statistic set at q= 0.05. The re-
sulting P-value threshold at this level was P<0.01. Post hoc
paired tests were performed between sessions within each
group separately, using the Wilcoxon signed-rank test, and
unpaired tests were also conducted between groups within
each session using the Kruskal-Wallis test.
For assessing linear relationships between changes in
psychological variables over time, raw change scores from
each self-report measure were firstly created by subtracting
scores in the first session from those in the second session.
This normalized the self-report data, allowing the use of
parametric statistics for further analyses. We also computed
residual change scores as a more conservative approach in
cases where there any correlations of raw change scores with
pretreatment scores, thus controlling for any regression-
to-the-mean effects. A series of regression analyses were
used to test whether improvement in mental health was
predicted by improvement in pain self-management and
control (“engagement,” “perceived control”), clinical pain
symptoms, as well as increases in self-reported mindfulness,
using both raw change and residual change scores. Results
were considered significant after correcting the P-values in
each analysis (raw change and residual change scores) sep-
arately using the FDR statistic set at q= 0.05. The resulting
P-value thresholds at this level were P< 0.03 for raw
change score statistics, and P< 0.02 for residual change
score statistics.
Preprocessing of EEG Data
EEG data were analyzed using the EEGLAB toolbox
(v4.515) running on MATLAB version 7.8. Preprocessing of
data was performed identically to that detailed elsewhere.25
Briefly, averaged ERPs covering the anticipation and pain
phases of neural activity were created for each participant
and each session, after the removal of linear trends in
the data and ocular artifacts (by removing artifactual
components after performing Independent Components Ana-
lysis), and filtering at 10 Hz low pass. ERPs were baseline-
corrected to either the 500-ms interval preceding the visual
anticipation cue (for the measurement of anticipatory-evoked
responses) or the 500 ms preceding the laser stimulus (for
measurement of the pain-evoked response). Data were ref-
erenced to the common average before proceeding further
with data analysis.
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236 |www.clinicalpain.com r2012 Lippincott Williams & Wilkins
Two 500-ms temporal periods of the anticipatory brain
response were extracted for analysis: an “early” period, at
2500 to 2000 ms preceding the laser stimulus, and a
“late” period, at –500 to 0 ms preceding the laser stimulus, as
detailed and justified elsewhere.25 The P2 peak of the laser-
evoked potential was also analyzed. For each participant and
condition, P2 peak latencies were determined at the electrode
for which the P2 peak showed maximum amplitude (Cz). An
averaged 20ms window of laser-evoked potential data was
then extracted, centered on this latency.
Analysis of ERP Data
For each temporal period (early anticipation, late an-
ticipation, P2 peak), the voltage at 5 electrodes were ex-
tracted for analysis of ERP amplitudes. The 5 electrodes
were those showing the peak amplitude over the whole
scalp for that time window, plus 4 adjacent electrodes. For
early anticipation these electrodes were POz, Oz, Pz, PO3,
and PO4; for late anticipation CPz, Cz, Pz, CP1, and CP2;
and for the P2 peak Cz, FCz, CPz, C1, and C2. We used a
nonparametric repeated-measures ANOVA (factors: group,
session) to identify main effects and interactions on the an-
ticipatory and pain-evoked potentials. The ANOVA was
performed once for each of the 3 time periods and for each of
the 5 corresponding electrodes, with a total of 15 compar-
isons. Results were judged to be statistically significant after
correcting for multiple comparisons using FDR, with a q
value of 0.05. EEG data are reported using 2-tailed statistics
because we did not specify a priori the direction of effects in
terms of the polarity of evoked responses and magnitude of
source activity.
Source Analysis of ERP Data
Sources of anticipatory and pain-evoked potentials
were estimated using the imaging approach to source re-
construction as implemented in SPM8 for MEG/EEG,
combined with custom MATLAB code for batch processing.
The method was used as detailed elsewhere.35 Briefly, an
FIGURE 1. A, Effects of the intervention on the anticipation-evoked potential at electrode CPz corrected to the preanticipation baseline
(3500 to 3000 ms), with early and late anticipation periods marked that were used for further analysis. B, Effects of the intervention
on the laser-evoked potential at electrode C2 after correcting to the prestimulus baseline (500 to 0 ms).
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r2012 Lippincott Williams & Wilkins www.clinicalpain.com |237
8196 vertex template cortical mesh was used as a forward
model, coregistered to the electrode positions of the stand-
ard 10-20 system. The lead-field of the forward model was
computed using the 3-shell BEM EEG head model available
in SPM8. Source estimates were computed on the canonical
mesh using 256 multiple sparse priors per hemisphere36
under group constraints.35 Source prior smoothness was set
at 1 mm. After calculating the source solution over antici-
pation and pain, 3-dimensional images were created from
averaged activity over smaller time windows that repre-
senting the specific time window of interest, calculated with
a Gaussian-weighted window [500 ms (FWHM) for early
and late anticipation and 40 ms for the P2 peak] centered on
the middle of the time interval. The resulting images were
smoothed at 10 mm FWHM.
Statistical analysis at the group level was performed
using conventional SPM ttests. To control for type I errors,
statistical parametrical maps were primarily thresholded at
P
voxel
< 0.05 (uncorrected) using RFT on the cluster level
(P
cluster
< 0.01, whole-brain FWE). In cases where clusters
were too small to reach this threshold but showed partic-
ularly high levels of voxel-level significance at P
voxel
< 0.01
(whole-brain FDR), these results are also reported. In the
first analysis, sources of brain activity activated and deac-
tivated during each time period were determined in a series
of tests on data averaged across groups in the first session
only. For early anticipation, late anticipation and the P2
peak separately, sources at each time period were contrasted
with sources during the baseline. In the second analysis,
groupsession interactions in the source activity during
each time period were tested using the Fstatistic, with post
hoc ttest comparisons. The statistical model included the
factors participant, group, and session. The following in-
dependence and equality of variance assumptions were used
in modeling. Participant and group were assumed to be in-
dependent observations, as they were not expected to covary
with each other, whereas session effects were considered not
independent in that they were likely to be correlated. Par-
ticipant and session were assumed to have equal error var-
iance, whereas group was assumed to have unequal variance.
This is because random allocation only guarantees equal
variances of pretreatment measurements, whereas unequal
variances of posttreatment measurements are often seen in
clinical trials.
Analyses of Volumes of Interest (VOIs)
We extracted data from VOIs identified in the previous
analyses [anticipation/pain (de)activations, and group
session interactions] as possible correlates of the self-report
variables. The following analyses were performed on VOIs
after subtracting activity between sessions (session 2 minus
session 1), and comparing with self-report measures sub-
tracted in the same way. The analyses were also completed
on residual change scores from the above measures. Linear
regression was used on the data pooled over both groups to
test whether neural activity in VOIs altered by the MBPM
was predictive of self-report variables. Of further interest
was the question of whether neural activity in VOIs that
predicted self-report variables acted as mediators of the
effects of the MBPM on these variables. Using a Sobel test
for mediation, results were considered significant at same
level as the corresponding regression statistics (derived
from FDR correction), which was P< 0.03 for raw changes
scores and P< 0.02 for residual change scores.
RESULTS
Self-report Outcomes
The MBPM resulted in statistically significant im-
provements in mental health (Table 2). There was also im-
proved engagement in pain self-management, and greater
perceived control over pain. These secondary outcomes were
significant predictors of improved mental health (Table 3).
There was a trend toward a reduction in affective clinical
pain scores in the treatment group that did not reach sig-
nificance in the interaction with the control group, but in post
hoc tests was significant for the MBPM group without the
control comparison. However, there was no significant effect
of the MBPM on ratings of acute experimental pain relative to
the control group (Table 2). According to the regression
analyses (Table 3), improvement in mental health was not
related to changes in clinical pain ratings (sensory or affective).
There was no evidence of improvement in physical health in
the intervention group, although there was improvement in the
control group, but this was not statistically significant in the
interactionwiththeinterventiongroup(Table2).
Increases in self-reported mindfulness were tested for
correlations with primary and secondary outcomes variables,
to provide evidence that improvement in these variables were
related to specific effects of the intervention rather than
nonspecific effects. Significant correlations were found be-
tween greater mindfulness and improved mental health (raw
change scores: r= 0.47, P< 0.01; residual change scores: r=
0.48, P< 0.01), engagement in self-management (raw change
scores: r= 0.75; P< 0.001; residual change scores: r=0.65,
P< 0.001), perceived control over pain (raw change scores:
r= 0.62, P< 0.001; residual change scores: r= 0.43, P<
0.02), and affective ratings of clinical pain (raw change
scores: r= 0.44, P< 0.02; residual change scores: r=0.41,
P< 0.03).
Treatment Effects on Anticipation
and Pain-evoked ERPs
The MBPM and control groups showed opposite pre-
to-post session effects on the anticipatory-evoked and pain-
evoked ERP response, with increases in both components
in the control group and decreases in both components in
the intervention group (Figs. 1A and B). During late an-
ticipation, significant group x session interactions were
found at electrodes CPz (P< 0.01) and CP2 (P< 0.01),
such that neural activity was decreased in the intervention
group compared with the control group. During the P2
peak, significant interactions were found at electrode C2
(P< 0.001), with the direction of change also being a rel-
ative decrease in the intervention group compared with the
control group. No significant effects were found during
early anticipation at the electrodes chosen for analysis.
Sources of Anticipation and Pain-evoked ERPs
Sources of the ERPs (Supplementary Table 1 and
Fig. 2A, Supplemental Digital Content 1, http://links.lww.
com/CJP/A39), which showed increases relative to baseline,
were as follows. During early anticipation, clusters of
neural activity were increased in right anterior insular,
dorsomedial prefrontal, anterior cingulate and subgenual
cingulate cortices. During late anticipation, similar sources
were found, but with larger contribution from bilateral
clusters of sources in the medial temporal lobe and neigh-
boring regions encompassing amygdala, putamen, anterior
insula, and ventrolateral prefrontal cortex. During pain
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processing (P2 peak), there were significant bilateral medial
temporal sources similar to those observed during late an-
ticipation, with the addition of a large cluster encompassing
mid-anterior cingulate cortex, extending to superior frontal
and parietal regions including the supplementary motor
area.
Sources of ERPs showing deactivations relative to
baseline (Supplementary Table 1 and Fig. 2B, Supplemental
Digital Content 1, http://links.lww.com/CJP/A39) common
to all time periods, were the left and right DLPFCs. During
early anticipation, additional deactivations were centered
on right secondary somatosensory cortex (S2) cortex and
the neighboring opercular-insular regions, and areas of the
middle occipital cortex and cuneus. During pain, additional
deactivations were in a region encompassing areas of the
posterior cingulate cortex and precuneus, and in medial
prefrontal cortex.
Treatment Effects on Sources of Anticipation
and Pain-evoked ERPs
Groupsession interaction effects on the ERP sources
were identified (Supplementary Table 1 and Fig. 2C, Supple-
mental Digital Content 1, http://links.lww.com/CJP/A39).
Notably, the regions that were significantly activated beyond
baseline were not affected by the intervention. Rather, re-
gions showing decreases in activity relative to baseline were
affected. During early anticipation, clusters were significantly
changed in the left and right DLPFCs, and in right S2 cortex.
The right DLPFC cluster extended into the right posterior
insula/S2 cortex. Post hoc analyses revealed these regions to
be decreased to a lesser extent in the intervention group rel-
ative to the control group from session 1 to session 2. During
late anticipation interactions were found in ventromedial
prefrontal and supplementary motor cortices, which were
decreased to a greater extent in the intervention group.
During the pain-evoked ERP, there was a significant inter-
action in a cluster including the left amygdala and anterior
insula, which showed both a nonsignificant decrease in the
intervention group and a larger increase in the control group.
Neural Correlates of Self-report Outcome
Variables
Improvements in mental health were significantly
predicted by less of a decrease in activity in left DLPFC and
right S2 cortex during early anticipation of pain (Table 3
and Fig. 2D). However, while these regions showed a trend
toward mediating the effects of the MBPM on mental
health outcomes, the analyses did not reach statistical sig-
nificance (using raw change scores: P< 0.04 for S2 cortex
and P< 0.07 for left DLPFC; using residual change scores:
P< 0.09 for S2 cortex and P< 0.14 for left DLPFC). Left
and right DLPFC and right S2 during early anticipation
were also tested as predictors of self-management outcomes
(Table 3 and Fig. 2D). Left DLPFC and right S2 were
strong predictors of perceived control over pain. Again, left
DLPFC (but not right S2) showed a trend toward media-
ting the effects of the MBPM on perceived control, but the
effect was not significant (P< 0.05 for raw change scores,
P< 0.06 for residual change scores).
DISCUSSION
The results of this study show that improvements in
the mental health of patients with musculoskeletal pain as
a result of mindfulness training are related to improved
perceived control and engagement in self-management of
pain, but not a reduction in pain symptoms. There was only
a small reduction in affective ratings of clinical pain as a
TABLE 2. Self-report Outcome Measure Statistics: Means (SD), and P-Values From ANOVAs and Post Hoc Tests
Mean (SD) Post Hoc Tests
Intervention Group Control Group Main Effects Session Effect Group Effect
Session 1 Session 2 Session 1 Session 2 Group Session Interaction Intervention Control Session 1 Session 2
Short-Form 36 Health Survey
Mental Health 58.4 (15.6) 75.3 (10.4) 61.5 (14.4) 58.2 (17.8) 0.08 0.01 0.00 0.01 0.15 0.31 0.02
Physical
Health
143.3 (86.4) 139.8 (82.6) 136.0 (56.1) 172.6 (67.1) 0.22 0.08 0.08 0.31 0.02 0.31 0.17
Pain Stages of Change Questionnaire (PSOCQ)
Engagement 20.0 (11.9) 37.9 (9.1) 21.5 (17.0) 23.6 (15.9) 0.09 0.00 0.00 0.00 0.14 0.43 0.01
Contemplation 40.0 (4.4) 40.1 (6.1) 39.0 (6.1) 38.7 (5.9) 0.12 0.44 0.49 0.43 0.26 0.11 0.18
Survey of Pain Attitudes Questionnaire
Perceived
control over
pain
10.5 (3.5) 14.1 (2.5) 11.0 (3.6) 10.8 (4.6) 0.09 0.01 0.01 0.01 0.47 0.47 0.02
Short-Form McGill Pain Questionnaire
Sensory pain 18.4 (5.8) 17.6 (7.1) 20.2 (6.6) 18.6 (7.1) 0.31 0.17 0.38 0.45 0.10 0.33 0.35
Affective pain 6.2 (3.7) 4.3 (2.6) 4.4 (3.8) 4.6 (4.3) 0.20 0.13 0.13 0.01 0.38 0.10 0.38
Laser pain
unpleasantness
ratings
5.4 (2.0) 5.9 (1.9) 5.9 (1.3) 6.3 (1.3) 0.19 0.18 0.42 0.35 0.18 0.17 0.32
Mindful
Attention and
Awareness
Scale
58.5 (14.2) 68.4 (9.5) 58.3 (11.5) 57.5 (13.8) 0.09 0.04 0.00 0.01 0.45 0.47 0.01
Value in italics are statistically significant.
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r2012 Lippincott Williams & Wilkins www.clinicalpain.com |239
result of the treatment, while there was no effect of the
treatment on ratings of acute experimental pain, and nei-
ther related to mental health outcomes. Changes in neural
activity were observed such that mindfulness training re-
duced deactivation (ie, increased activation) of central ex-
ecutive regions of the brain (particularly, bilateral DLPFC)
during anticipation of acute pain, without affecting regions
that normally correlate with pain intensity such as the
cingulate and posterior insula cortices. There were mild
reductions in emotional processing regions including the
amygdala and anterior insula, but improvements in psy-
chological outcomes (mental health, perceived control, and
engagement in pain self-management) were rather related to
the greater anticipatory processing in DLPFC and somato-
sensory cortices.
Self-report Outcomes
As expected, the self-reported mental health of patients
enrolled in the MBPM improved as a result of the inter-
vention. The MBPM also increased patient perceptions that
their pain was controllable and manageable, effects that
correlated with the improvements in mental health, without
a significant reduction in clinical pain symptoms. Although
there was evidence of a reduction in affective ratings of
clinical pain within the MBPM group, this effect did not
reach significance relative to the control group, and was not
related to improvements in mental health. Hence, within
2 weeks post-intervention, mental health was more closely
related to the perception of pain as being manageable than a
reduction in pain symptoms. This is consistent with the aims
of mindfulness meditation, which are to improve the ability
to regulate and self-manage the response to pain rather than
the sensation of pain. This highlights that fact that the term
“perceived control over pain” needs to be interpreted within
a broader biopsychosocial context than simply control over
pain sensation. Perceived control can have different mean-
ings depending on whether it is the sensory aspects of the
pain or broader emotional/behavioral aspects and responses
to the pain that are perceived as being better managed.
This study was not a clinical trial of the intervention,
but rather an investigation of how the intervention exerts
beneficial effects on mental health in patients with chronic
pain. Yet, the lack of an active control group, as would be
used in a clinical trial to control for placebo effects, is a
limitation of the design. This means we cannot discount a
number of possible influences on the MBPM group results
that are known to contribute to placebo effects, including
patient expectations, therapist attention and group social
support. Other limitations include that the ratio of females to
males was higher in the intervention group, and that we did
not measure education level and pain duration, which may
have been unbalanced in the 2 groups and possibly may have
affected the study outcomes. Although these are valid con-
cerns, the current data showing relationships between the
main outcomes of interest and the outcomes from the
mindfulness scale encourage an optimistic view of the results.
Self-reported mindfulness was found to correlate with im-
provements in mental health and pain self-management
outcomes, as well as reductions in affective ratings of clinical
pain. The data provide assurance that improvements in the
main outcomes of the study were related to the specific psy-
chological processes targeted by the intervention, although
further work is warranted to more robustly control for pos-
sible placebo effects. These data also confirm previous re-
ports8,37 that mindfulness is related to emotional functioning
in patients, and suggests that mindfulness may empower
patients to manage their symptoms better.
On a note of caution, any research study, including the
present study, which relies on patients’ subjective reports of
their pain and responses to pain, assumes that patients have
paid adequate attention to their subjective states to be able
to provide accurate reports. Such assessments may be
measuring patient beliefs and desires about their experi-
ences rather than the actual lived experiences. It therefore
follows that we cannot determine for certain whether par-
ticipants were attending to pain unpleasantness during the
experimental pain procedure, and we settled for asking for
ratings of unpleasantness ratings on a 0 to 10 pain scale as a
way of encouraging attention to pain unpleasantness and
accurate reporting. It may have been potentially useful to
debrief patients after the experiment to find out what they
were attending to during the experiment, to see whether
they were able to engage with that task, although this also
suffers the limitation of being a better gauge of patients’
TABLE 3. Regression Analyses of Self-report Outcomes and Their Neural Correlates
Raw Change Scores Residual Change Scores
Dependent Variables Independent Variables bt-Value P-Value R
2
bt-Value P-Value R
2
Self-report outcomes
Mental health Engagement 0.51 3.03 0.00 0.26 0.52 3.08 0.00 0.27
Perceived control 0.46 2.58 0.01 0.21 0.46 2.67 0.01 0.22
Sensory clinical pain 0.07 0.35 0.36 0.00 0.02 0.11 0.46 0.00
Affective clinical pain 0.26 1.36 0.09 0.07 0.26 1.38 0.09 0.07
Neural correlates of self-report outcomes
Mental health Left DLPFC 0.44 2.49 0.01 0.19 0.40 2.22 0.02 0.16
Right DLPFC 0.42 2.39 0.01 0.18 0.25 1.33 0.10 0.06
Right S2 0.49 2.84 0.00 0.24 0.51 3.01 0.00 0.26
Engagement Left DLPFC 0.37 2.00 0.03 0.13 0.42 2.35 0.01 0.17
Right DLPFC 0.20 1.05 0.15 0.04 0.30 1.62 0.06 0.09
Right S2 0.39 2.19 0.02 0.16 0.55 3.34 0.00 0.30
Perceived control Left DLPFC 0.50 2.91 0.00 0.25 0.48 2.78 0.00 0.23
Right DLPFC 0.20 1.06 0.15 0.04 0.19 1.01 0.16 0.04
Right S2 0.47 2.72 0.01 0.22 0.43 2.45 0.01 0.19
Value in italics are statistically significant.
DLPFC indicates dorsolateral prefrontal cortex; S2, secondary somatosensory cortex.
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240 |www.clinicalpain.com r2012 Lippincott Williams & Wilkins
beliefs or desires than an accurate measure of engagement.
These limitations would benefit from more objective meas-
urement of responses to pain, and is one justification for the
use of neurobiological indicators of pain in this study.
Electrophysiological Outcomes
One aim of this study was to improve our under-
standing of the neurobiological changes associated im-
provements in pain responding. In this study we used acute
experimental laser pain as a proxy for patient’s clinical
pain, which had the advantage of being able to separate out
anticipatory activity (related to expectations and beliefs)
from pain-evoked activity, but the disadvantage of having
a different meaning to the patient (likely being less dis-
tressing) than their clinical pain. The EEG results showed
that, as expected, the DLPFCs were modified by mindful-
ness training. Unexpectedly, changes were also found in S2
cortex. These regions were normally deactivated during
early pain anticipation in both intervention and control
groups. The effect of the MBPM was to cause DLPFC
and S2 cortex to be less deactivated during the early phase
of anticipation than normal. Effectively, the intervention
stabilized activity in these regions so that they were less
affected by the anticipation of pain.
The meaning of the reduced deactivation, rather than
simply activation, requires careful interpretation. Deacti-
vations occurring due to task-related demands are normally
associated with the “default mode” network, involved with
internal mentation or “daydreaming,” which is considered
to include the medial temporal lobes, posterior cingulate
cortex, and medial prefrontal cortex.38–40 The posterior
cingulate and medial prefrontal cortices were indeed deac-
tivated in this study across groups and sessions during the
pain response, but not during anticipation. But the regions
of interest, DLPFC and S2, are not considered part of the
default mode network. Rather, DLPFC is considered part of
an executive network that is anti-correlated with default mode
brain regions,38,41 whereas S2 cortex activates in response to
task-related demands to process somatosensory information,
including pain.42,43 Reduced deactivation of these regions
could therefore indicate the maintenance of cognitive control
and task-related processing of somatosensory information
during anticipation of pain. This interpretation is consistent
with the component of mindfulness training involving learn-
ing to maintain present-focused attention, particularly on
body sensations, even during difficult experiences such as pain
that may encourage a more distracted mental state as a
coping strategy. Indeed, increases in DLPFC and S2 activity
have been shown to occur during states of mindfulness
meditation.19,21 Further, activation of these regions occurs in
individuals without previous mindfulness training who are
given instructions to pay attention “mindfully”, that is, with a
present-focus on the raw sensory experience, rather than
thinking about theexperienceinamorementally distracted,
or ruminative, way.44
Because mindful present-focus reduces rumination on
emotional experiences, it can be considered an emotional
regulation strategy. The DLPFC has been shown to activate
when participants are asked to re-appraise emotional stimuli
by focusing on non-emotional aspects of the experience.23,45,46
The DLPFC is thought to be important for emotional reg-
ulation by inhibiting conditioned emotional responses,22 in
association with reductions in neural activity in the insula and
amygdala.47 These interactions are thought to dampen the
affective response to pain.47,48 This is consistent with the
findings from this study that the MBPM group showed
a small reduction in affective pain ratings (although not sig-
nificant in the interaction between group and session),
whereas sensory pain ratings remained unchanged. In addi-
tion, during late anticipation, the MBPM either decreased or
FIGURE 2. ERP sources showing (A) increases and (B) decreases
relative to the preanticipation baseline from session one, averaged
across both groups. C, Brain regions showing significant effects in
the groupsession interaction. D, Neural activity predicting scores
on self-report outcome measures (subtracted scores: session 2 mi-
nus session 1). Amyg indicates amygdala; DLPFC, dorsolateral
prefrontal cortex; DMPFC, dorsomedial prefrontal cortex; Ins, in-
sula; MCC, midcingulate cortex; Put, putamen; sACC, subgenual
anterior cingulate cortex; SMA, supplementary motor area; S2,
secondary somatosensory cortex; VMPFC, ventromedial prefrontal
cortex.
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preventedanincreaseinneuralactivityinregionsincluding
the amygdala, anterior insula, and ventromedial prefrontal
cortex. These regions have previously associated with con-
ditioned fear and anticipatory anxiety.49–51 The results from
the present study, combined with the results from previous
work, are consistent with the hypothesis that mindfulness
recruits the cognitive control mechanisms of DLPFC. This
region was related to the improvements in mental health in
our study, consistent with their known role in regulating
emotional responses. However, we were not able to demon-
strate a mediatory role for DLPFC in the therapeutic out-
comes; indeed any such analysis would be based on
correlative relationships that cannot prove causation without
specific manipulation of the brain regions involved.
Interestingly, S2 cortex activity during early antici-
pation of pain also predicted improvements in mental
health and measures of pain control and self-management.
This finding might appear curious as S2 cortex is not con-
sidered a region involved with emotional regulation or
other aspects of cognitive control. S2 cortex does activate
during anticipation of pain,25 an effect that may be related
to expectancy of pain,52,53 which normally modulates the
subsequent pain experience.54 However, expectancy effects
normally co-occur with activation in other regions such as
the cingulate and insula cortices,52,53 which we did not
observe, nor did we see a change in acute experimental pain
perception. A more likely explanation than a change in
expectancy, which would be consistent with the aims and
practices of mindfulness meditation, is that greater S2 ac-
tivity resulted from a greater tendency after mindfulness
training to attend to the quality of body sensations. It is an
open question as to whether this region is involved in the
regulation of cognition and emotion. We speculate that its
greater activity during anticipation of pain after mindful-
ness training is more likely to be a consequence of greater
emotional regulatory processes taking place elsewhere, for
example in higher-order brain regions such as DLPFC. The
strong correlations of increased activity in S2 cortex with
outcome measures including mental health suggests that
this greater S2 cortex activity may turn out to be a useful
surrogate of improved emotional regulation resulting from
meditative concentration on body sensations, but we can-
not at present consider it causally related.
Although early anticipatory DLPFC and S2 activity
had clear correlates with pain self-management/control and
mental health, additional findings of interactions between
session and group factors during late anticipation in ven-
tromedial prefrontal cortex and supplementary motor area
did not have such correlates. These interactions resulted
from both decreases in the intervention group and increases
in the control group, and explain well the observed effects
on the amplitude of the anticipatory potential during late
anticipation, which was increased in the control group and
decreased in the intervention group. Further effects were
also found in the control group: during the experience of
acute laser pain (P2 peak), interactions between group and
session were observed in a cluster including the amygdala
and anterior insular cortex, which resulted from increases
in the control group when there was no change in the
intervention group. These results were also not related to
self-report outcomes. It is possible that the increased brain
activity during both anticipation and pain in the control
group could be caused by fear conditioning toward the
experimental procedure. In other words, conditioned fear
may augment the neural processes of negative expectancy,
thereby affecting the processing of the pain stimuli. Pre-
vious studies have shown amygdala and anterior insular
cortex in particular to be part of a network that develops
conditioned fear responses to stimuli, including pain stim-
uli.49,55–57 We speculate that control group participants
may have more fearfully anticipated the pain stimuli in the
second session having attended the first session a number of
weeks earlier, an effect that appears to be absent in the
MBPM group.
However, a limitation of this study is that acute pain in
an experimental setting, where pain induction is very brief
and episodic, could be considered very different from the
characteristics of chronic pain, likely resulting in different
response patterns. Although there are significant advantages
to the use of acute pain models for this type of study, namely
the ability to keep pain constant between 2 experimental
sessions, there is a possibility that the treatment outcome
results from this study are in fact not causally related to the
effects shown of mindfulness training on acute pain re-
sponding. However, we do know that experimental pain and
ongoing clinical pain are processed within the same struc-
tures within the pain matrix.58 Although there is greater
processing of clinical pain within the medial pain system
during clinical pain consistent with its greater emotional
salience,58 it is difficult to imagine that entirely different
control processes are operating during the different types of
pain. Despite this, we would suggest caution in drawing
causal attribution from the current results which should be
interpreted as purely correlational at this stage.
Relationship to Previous Studies
The results of this study can be contrasted with other
published experimental data showing effects of mindfulness
meditation on pain perception and processing. Our previous
study25 used the same experimental protocol, except that we
studied, in a single session, a group of healthy participants
with a range of past experience in meditation. Meditation
experience was associated with lower perceived pain un-
pleasantness and related neural processing of pain antici-
pation in the cingulate cortex, with less subsequent pain
processing in the insula. Other studies investigating rela-
tionships between meditation expertise (in advanced practi-
tioners) and pain processing have also shown that meditation
is associated with less processing in regions such as insula
and ACC.59,60 In the current study, the MBPM group
showed lower affective ratings of clinical pain after treatment
but this did not reach significance in the interaction between
group and session. We also found no evidence of a reduction
in neural processes within pain intensity processing regions
such as insula and cingulate cortex after the MBPM. Pre-
vious studies of advanced meditation practitioners have also
shown increases in S2 cortex activity60 and increased gray
matter in S2 cortex that correlates with lower pain sensi-
tivity.61 This is consistent with our findings of increased an-
ticipatory activity in S2 cortex after mindfulness training.
It is possible that significant reductions in activity in
pain intensity-related brain regions such as the cingulate
and insula cortices only may become observable with longer
training than took place in this study, as the reduction in
anticipatory pain processing in our previous study was
most apparent in participants with years of meditation ex-
perience.25 A reduction in pain may therefore only occur
secondarily to improvements in mental health, and over a
longer time scale. This conclusion may appear to be in-
consistent with research by other groups62,63 that have
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242 |www.clinicalpain.com r2012 Lippincott Williams & Wilkins
shown effects of meditation training on reduced pain per-
ception and neural processing of pain in healthy partic-
ipants after only very short-term training of a few days.
However, our experimental approach differed in that we
measured neural activity in patients with chronic pain, and
while they focused on the unpleasantness of the experienced
pain rather than asking them to withdraw attention toward
an object of meditation, as was done in the research
showing significant short-term effects.62,63 We therefore
suspect that our results are more reflective of long-term
(trait) changes in pain processing that are not dependent on
temporary states of meditation, although this must be
considered speculation at this point.
CONCLUSIONS
The study supports the hypothesis that mindfulness
training provides a cognitive strategy for improving pain
management, which has positive consequences for mental
health. Our results show that this is related to maintaining
activity in central executive regions responsible for emotional
regulation (DLPFC) during anticipation of pain, whereas
reductions in processing during pain experience were modest
and restricted to regions that are known to mediate emotional
responses to pain including the amygdala and anterior insula.
Although the effects on neural activity were measured in re-
lation to acute pain, the effects were related to clinical out-
comes, suggesting that the acute pain model may be useful for
understanding the effects of mindfulness training on neural
activity related to pain management. However, the longer-term
effects of mindfulness training on clinical pain or its manage-
ment cannot be determined from this study, nor is it clear the
extent to which the current results include effects related to
placebo. We consider that this study provides some valuable
insights into short-term functional changes pain processing
related to improvement in mental health. Further studies are
required with longer follow-up periods to understand the po-
tential long-term effects of mindfulness training on neural
networks related to cognitive control and emotional regu-
lation, and with placebo controls to help distinguish therapy-
specific effects on nociceptive processing from those of placebo.
ACKNOWLEDGMENT
The authors are grateful for the support of Breathworks
CIC in helping to conduct the research.
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... ACT interacts with thoughts and emotional distress so that people do not perceive them as a symptom of a disease or even takes it in a way that they are harmless (even if they are upset or unpleasant). [22] The main message of ACT is the acceptance of something that is beyond the control of the individual and committing to do everything under control of the person. [23] With these interpretations, acceptance-based treatment can improve the conditions of chronic patients, including those suffering from MS. ...
... Since no research has taken place previously on the effects of ACT on life expectancy, consonant researches do not exist directly. However, given that decrease of hope in people with depression is a clear feature of disease, the results of the hypothesis are consistent with the research of Buhrman et al., [19] Powers et al., [20] Mc Crachen and Gutierrez, [21] Brown and Jones [22] titled as " the Overall Effectiveness of Treatment Based on Acceptance and Commitment on Depression and Anxiety in Patients with Chronic Pain" as well as researches of Rajabi et al. [23] titled as "the Efficacy of ACT in Reducing Anxiety and Depression Among Females with MS", and Abedini et al. titled as "the Effectiveness of Hope Therapy in Increasing Expectancy, Reducing Depression, and Improving the Quality of Life in Women with MS". ...
Article
Full-text available
Context: MS is a chronic and debilitating disease, in which the immune reactions damage myelin sheath of axons in the central nervous system. Psychological consequences of MS and the treatment have been the subject of many research activities Aims: The present study examines the effectiveness of acceptance and commitment therapy (ACT) based on the life expectancy in patients with multiple sclerosis (MS). Setting and Design: This study was a randomized clinical trial and conducted from September 2016 to May 2017 in the MS patients of North Khorasan Province and Shirvan city in 2016. Methods and Material: This is an applied and quasi experimental research with pretest, posttest, and control group. Using the available sampling method, 30 samples were selected by random assignment and included in experimental and control groups (15 people per group). The instrument used in this study was Schneider's life expectancy questionnaire. The experimental group received eight sessions of therapeutic intervention. Statistical Analysis Used: We used mean and standard deviation, regression line, analyze covariance to analysis of data. Results: The results of covariance analysis showed that ACT significantly improves life expectancy in patients with MS. Conclusions: According to the results, it is expected that ACT maintains its effects in the long run with features such as encouraging people to live in the present moment, mindfulness, commitment to the pursuit of worthwhile goals, and an emphasis on process rather than the outcome.
... Psychometric questionnaires included the Perceived Stress Scale (PSS; (Cohen et al., 1983)), the State Anxiety Inventory (STAI-Y form; (Vigneau and Cormier, 2008)), and the Mindful Attention Awareness Scale (MAAS; (Brown and Jones, 2013)). ...
... circuits exerting an emotion regulation onto the amygdala, one of the brain structures that is known as highly relevant for emotional processing (Kral et al., 2018). Studies have shown that Mindfulness practice improves executive brain functioning and increases activation of prefrontal cortical areas (PFC) -specifically dorsolateral (DLPFC), ventrolateral (VLPFC), dorsomedial (DMPFC) -and insula during the expectation, but not the perception of negative stimuli (Brown and Jones, 2013;Opialla et al., 2015). Interestingly, once activated, mindful processing may no longer require activation of prefrontal areas. ...
Article
Objective Mindfulness practice, a form of meditation, has shown benefit for psychological and physical health. In this study, we investigated the effect of an intensive period of Mindfulness practice on some biological mediators of stress and inflammation during a 3-day residential retreat. Methods A total of 95 healthy individuals (aged 18–67) were recruited and randomized to a Mindfulness retreat arm or an active control arm. Before (t0) and after (t1) the intervention, all the participants were assessed for salivary cortisol levels and for a panel of pro- and anti-inflammatory cytokines measured in saliva. Psychometric measures on stress, anxiety and awareness were carried out using PSS, STAI-Y and MAAS questionnaires, respectively. Results As to the within-group differences, we observed a statistically significant decrease in perceived stress (β= -8.85, p<0.0001), and anxiety scores (β= -12.39, p<0.0001), while awareness increased (β= 15.26, p<0.0001) between t0 to t1 in retreat participants. In the mindfulness intervention group, we also observed a statistically significant reduction in the levels of pro-inflammatory cytokines IL-6 (β= -0.94 p=0.001) and IL-8 (β= -176.40, p<0.0001), and an increase in anti-inflammatory IL-10 (β=0.89 p<0.0001) levels at the end of the retreat. At t1 we observed a highly significant correlation between cortisol levels and both anxiety (r=0.56, p <0.0001) and perceived stress (r=0.92, p< 0.0001) scores. Conclusions Mindfulness retreat participants showed a significant reduction in perceived stress and anxiety levels, as well as an improved balance of some key mediators of inflammatory states. Our data provide evidence that a mindfulness retreat may be effective in improving physical and mental health. Future studies with larger numbers of subjects and follow-up periods may examine mindfulness practice as a non-pharmacological alternative to promote stress reduction and overall health and wellbeing.
... However, there was nothing noticeable in terms of physical pain. Worth mentioning is that Brown and Jones found in their research with patients who had chronic pain, that there was an improvement in mental health and better management of pain, while clinically no reductions in pain rating had been found [39] . ...
Article
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Mindfulness Based Stress Reduction (MBSR) has been extensively applied as a clinical intervention by researchers' who have made on-the-spot decisions research as part of their practice. This research was provided via a knowledge transfer of 8 weeks of MBSR based on the original MBSR version. The main objective of this study was to offer a qualitative explorative insight into the perceived experience of participating in a MBSR program for injured athletes. A semi structured interview was conducted with each injured athlete who participated in this study. A thematic analysis was applied to explore the themes which emerged from injured athletes' experience after 8 weeks of participation in a MBSR program. Five themes emerged from injured athletes' attitudes towards MBSR: 1) Reconnecting with the body, 2) Reconnecting with the mind, 3) Passivity of MBSR as opposed to the athletic praxis, 4) Group versus self-guided MBSR, 5) Acceptance of pain. These different themes are presented and discussed below. This particular qualitative exploratory investigation was based on injured athletes' experiences in this study; MBSR can benefit them during the sport rehabilitation process. As such, the findings will promote scientific understanding about the effectiveness of MBSR as a clinical intervention. It should also be noted that, more investigation is required to find out about the role of mindfulness meditation in terms of therapeutic aspects with injured athletes.
... However there is no direct study comparing the effects of tDCS with rTMS in patients with FM. In addition, since most of the previous studies have investigated M1, there are insufficient data to draw a conclusion regarding the efficacy of these neurostimulation techniques over DLPFC [32,35,54] while the mechanism of FM has been proposed to be related to the abnormalities of top-down processing of pain anticipation networks, which would relate to DLPFC rather than M1 [10,32]. Therefore, this study was conducted to compare the effect of these two different noninvasive brain stimulation techniques over DLPFC in the management of patients with FM. ...
Article
Objectives: The aim of this study was to compare the effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) on pain and quality of life in patients with fibromyalgia. Methods: Thirty participants were randomized into two groups of 15 patients, to receive 3 sessions of either high-frequency (10 Hz) rTMS or 2 mA, 20 min anodal transcranial direct current stimulation over the left dorsolateral prefrontal cortex (DLPFC) over 1 week. Pain was assessed using a Visual Analog Scale (VAS) before treatment, immediately after treatment, 6 and 12 weeks later. Quality of life was evaluated using the Revised Fibromyalgia Impact Questionnaire (FIQR) and psychiatric symptoms were measured using the Depression Anxiety Stress Scale-21 Item (DASS-21) before treatment, and 6 and 12 weeks after treatment. Results: For the VAS there was a significant time-group interaction, showing that the behavior of two groups differed regarding changes of VAS in favor of the RTMS group (df = 1.73, F = 4.80, p = <0.016). Time-group interaction effect on DASS-21 and FIQR was not significant. 66.6% of patients in rTMS group and 26.6% of patients in tDCS group experienced at least a 30% reduction of VAS from baseline to last follow-up (p = 0.028). Discussion: With the methodology used in this study, both rTMS and tDCS were safe modalities and three sessions of rTMS over DLPFC had greater and longer lasting analgesic effects compared to tDCS in patients with FM. However, considering the limitations of this study, further studies are needed to explore the most effective modality.
... However there is no direct study comparing the effects of tDCS with rTMS in patients with FM. In addition, since most of the previous studies have investigated M1, there are insufficient data to draw a conclusion regarding the efficacy of these neurostimulation techniques over DLPFC [32,35,54] while the mechanism of FM has been proposed to be related to the abnormalities of top-down processing of pain anticipation networks, which would relate to DLPFC rather than M1 [10,32]. Therefore, this study was conducted to compare the effect of these two different noninvasive brain stimulation techniques over DLPFC in the management of patients with FM. ...
Article
Purpose of the study: Pelvic floor muscles dysfunction is one of the most important etiologies of coccydynia, therefore, manual therapies have been proposed as the first line of treatment. The purpose of this study was to investigate the effect of biofeedback as a new approach in the treatment of coccydynia. Methods: Thirty women were randomized into two groups. Both groups were injected with corticosteroid. One group received pelvic floor muscle exercises plus biofeedback while the other only performed exercises. Patient’s pain was measured using Visual Analogue Scale (VAS) in the first visit and after 1, 2 and 6 months of follow-up as well as Dallas pain and SF-36 quality of life questionnaires before and 2 months after the treatment. Results: Pain had improved significantly after 1, 2 and 6 months in both groups compared to the baseline. However, the amount of change was not different between the groups at any time interval. The results were the same for Dallas pain scale and SF-36 quality of life questionnaire. Conclusion: Adding biofeedback to pelvic floor muscle exercises did not lead to any further improvement in management of chronic coccydynia. Further studies with larger sample sizes may show the effect of biofeedback more clearly.
... Cortical thickness in the SII and insular was also found to predict pain threshold in expert meditators (Grant et al. 2010). Similar results were also found in two EEG studies of participants at rest, with MM experts in one study showing lower pain-evoked responses in the SII and posterior insular compared to controls (Brown and Jones 2013), and another study reporting higher activity in the SII and insular post-meditation training for novices (Brown and Jones 2010). In a fMRI study directly comparing experts and novices during meditation, pain-evoked activity in the posterior insular and SII was not significantly different between groups (Lutz et al. 2008). ...
Article
Full-text available
Objectives Mindfulness meditation (MM) is an attention and acceptance–based intervention effective for managing chronic pain. Current literature predominately focuses on the behavioral effects of short-term mindfulness-based programs for pain reduction. However, the long-term potential of MM and its effect on pain processing are less well understood. Furthermore, it is possible that short- and long-term effects of MM are underpinned by different neural processes. This systematic review was undertaken to better understand the short- and long-term effects of MM on brain processes related to pain by comparing pain-related neural process in novice and expert MM. Methods A literature search was performed to identify relevant studies using MRI/fMRI and EEG/MEG. Results A total of 14 studies were selected: 1 MEG and fMRI, 5 EEG, and 8 MRI/fMRI. Overall, findings across studies are consistent in reporting reduced pain ratings in both novice and expert meditators. However, different brain processes appeared to underlie this effect with experts showing greater activity in the somatosensory regions and novices showing reduced activity. The available evidence also indicates a greater dissociation between pain salience and pain unpleasantness in expert meditators along with greater changes in the respective brain regions, suggesting a dissociation between sensory and the cognitive-affective dimensions of pain. For novice meditators, however, the evidence is less conclusive. Conclusions Given the ongoing nature of chronic pain, the long-term effects of mindfulness meditation should be explored to assess whether the effects of short-term programs remain post treatment.
... Mindfulness programs have given high visibility to bring the impact of the practice through a well-structured protocol that can be replicated over the years offering many clinical benefits as well as a greater understanding of neurophysiological mechanisms from immediate and long-term practice [1][2][3][4][5]. Since then, several protocols have been created to give specificity to the public suffering from mental health problems such as depression and anxiety (MBSR, MBCT), addicts (MBRP), eating disorders (MB-EAT), pain and chronic illness (MBPM). ...
Article
Chronic pain is a leading cause of disability in the United States. Limited efficacy associated with pharmacologic management and surgical interventions in refractory patients has led to further exploration of cognitive and behavioral interventions as both an adjunctive and primary therapeutic modality. Mindfulness-based meditation has shown to be effective in reducing pain in randomized studies of chronic pain patients as well as models of experimentally induced pain in healthy participants. These studies have revealed specific neural mechanisms which may explain both short-term and sustained pain relief associated with mindfulness-based interventions.
Article
Most patients with chronic pain do not find adequate pain relief with a single treatment, and accumulating evidence points to the added benefits of rational combinations of different treatments. Given that psychological therapies, such as mindfulness-based interventions (MBIs), are often delivered in conjunction with concomitant analgesic drug therapies (CADTs), this systematic scoping review examines the evidence for any interactions between MBIs and CADTs. The protocol for this review has been published and registered. MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, and PsycINFO databases were searched until July 2019. We included randomized controlled trials that evaluated the efficacy of MBIs for the treatment of chronic pain. A total of 40 randomized controlled trials (2978 participants) were included. Thirty-nine of 40 (97.5%) included mindfulness-based clinical trials allowed the use of CADTs. However, only 6 of these 39 (15.4%) trials provided adequate details of what these CADTs were, and only 4 (10.3%) trials controlled for CADTs. Of great relevance to this review, none of the included trials analyzed the interactions between MBIs and the CADTs to determine whether they have an additive, synergistic, or antagonistic effect on chronic pain. Adverse events were inconsistently reported, and no judgment could be made about safety. Future trials assessing the interactions between MBIs and CADTs, with better harms reporting, are needed to better define the role of MBIs in the management of chronic pain.
Article
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The subjective experience of one's environment is constructed by interactions among sensory, cognitive, and affective processes. For centuries, meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events. To better understand how meditation influences the sensory experience, we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants. After 4 d of mindfulness meditation training, meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57% and pain intensity ratings by 40% when compared to rest. A two-factor repeated-measures ANOVA was used to identify interactions between meditation and pain-related brain activation. Meditation reduced pain-related activation of the contralateral primary somato-sensory cortex. Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions. Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula, areas involved in the cognitive regulation of nociceptive processing. Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation, an area implicated in reframing the contextual evaluation of sensory events. Moreover, reductions in pain unpleasantness also were associated with thalamic deactivation, which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas. Together, these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information.
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Psychotherapy is used commonly to treat a variety of mental illnesses, yet surprisingly little is known about its biological mechanisms especially in comparison with pharmacotherapy. In this review we survey the current knowledge about changes in brain function following psychotherapeutic intervention that are detectable with current neuroimaging techniques. We also consider the possible role for neuroimaging in refining clinical diagnoses and predicting treatment outcome, which would benefit both clinical decision-making and the cognitive neuroscience of psychotherapy.
Article
Study Design. A literature review was conducted. Objective. To examine the outcome of behavioral (BT) and cognitive–behavioral treatment (CBT), collectively referred to as BT-CBT, for chronic pain, to identify the predictors of treatment outcome, and to investigate the change processes associated with these treatments. Summary of Background Data. Numerous controlled clinical trials of BT-CBT for chronic pain, alone or more commonly in multidisciplinary treatment contexts, suggest that these treatments are effective. However, further study is needed to examine which outcome variables change, when, for whom, and how. Methods. Published literature was gathered from Medline, PsychLit, and searches of relevant journals. Results. Overall, BT-CBT for chronic pain reduces patients’ pain, distress, and pain behavior, and improves their daily functioning. Differences across studies in sample characteristics, treatment features, and assessment methods seem to produce varied treatment results. Also, some patients benefit more than others. Highly distressed patients who see their pain as an uncontrollable and highly negative life event derive less benefit than other patients. Decreased negative emotional responses to pain, decreased perceptions of disability, and increased orientation toward self-management during the course of treatment predict favorable treatment outcome. Conclusions. Current BT-CBT helps many patients with chronic pain. Continuing clinical research should improve the matching of treatments with patient characteristics and refine the focus of treatments on behavior changes most associated with positive outcome. Further study of fear, attention, readiness to adopt self-management strategies, acceptance of pain, and new combinations of interdisciplinary treatments may lead to improved interventions.
Article
This chapter focuses on pure rank statistics in factorial designs. Pure rank statistics are invariant under any strict monotone transformation of the data and are robust against outliers. In addition, they are applicable to ordinal data such as scores in psychological tests, grading scales to describe the degree of the damage of plants or trees in ecological or environmental studies. The classical models of analysis of variance are generalized (ANOVA) in such a way that not only the assumption of normality of the error terms is relaxed but also the structure of the designs is introduced in a broader framework. In addition, the concept of treatment effects is redefined within this framework. To identify the testing problem underlying the different rank procedures, the relations between the hypotheses in the general model and in the standard linear model are investigated in the chapter. The chapter concludes with a discussion of random-factor model along with the rank procedures for heteroscedastic mixed models.