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Abstract

Is the placebo effect something to think about in the Mindfulness-based interventions for chronic pain? We are still at the onset of this fascinating road but there is something to be considered, as shown by this systematic review

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TYPE Systematic Review
PUBLISHED 29 August 2024
DOI 10.3389/fnint.2024.1432270
OPEN ACCESS
EDITED BY
Steen Schulz,
Charité University Medicine Berlin, Germany
REVIEWED BY
Jonathan Davies,
The University of Melbourne, Australia
Shalini Bhattacharya,
University College London, United Kingdom
*CORRESPONDENCE
Isaura Tavares
isatav@med.up.pt
RECEIVED 13 May 2024
ACCEPTED 11 July 2024
PUBLISHED 29 August 2024
CITATION
Lopes A, Sampaio R and Tavares I (2024) Pain,
mindfulness, and placebo: a systematic
review. Front. Integr. Neurosci. 18:1432270.
doi: 10.3389/fnint.2024.1432270
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©2024 Lopes, Sampaio and Tavares. This is
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permitted which does not comply with these
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Pain, mindfulness, and placebo: a
systematic review
Alexandra Lopes1, Rute Sampaio1,2 and Isaura Tavares1,3,4*
1Department of Biomedicine, Unit of Experimental Biology, Faculty of Medicine, University of Porto,
Porto, Portugal, 2CINTESIS—Centre for Health Technology and Services Research, Porto, Portugal,
3IBMC-Institute of Molecular and Cell Biology, University of Porto, Porto, Portugal, 4I3S-Institute of
Investigation and Innovation in Health, University of Porto, Porto, Portugal
Introduction: Pain is a complex phenomenon influenced by psychosocial
variables, including the placebo eect. The eectiveness of mindfulness-based
interventions (MBIs) for pain has been demonstrated in experimental studies
and systematic reviews, but the mechanisms of action are only starting to be
established. Whether the expectations of individuals experiencing pain can be
manipulated during MBIs remains to be systematically evaluated, and what role
placebo eects might play remains to be explored.
Methods: To evaluate the literature analyzing placebo eects in MBIs for pain,
we performed a systematic review based on searches conducted in PubMed,
Web of Science, and SCOPUS databases. Our search revealed a total of 272
studies, of which only 19 studies were included (10 acute pain and nine chronic
pain), considering the inclusion and exclusion criteria related to expectations and
placebo eects.
Results: From the 19 included studies, six measured placebo eects only in
relation to the pharmacological intervention used in the study and not to an MBI.
Discussion: The results of the few studies that focused on the placebo eects of
the MBIs indicate that placebo and expectations play a role in the MBIs’ eects
on pain. Although expectations and placebo eects are frequently discussed in
the context of mindfulness and pain research, these results show that these
factors are still not routinely considered in experimental designs. However,
the results of the few studies included in this systematic review highlight a
clear role for placebo and expectancy eects in the overall eects of MBIs
for both acute and chronic pain, suggesting that routine measurement and
further consideration in future studies are warranted. Additional research in this
fascinating and challenging field is necessary to fully understand the connection
between MBIs, placebo/expectations, and their eects on pain relief.
KEYWORDS
expectations, cognitive-behavioral therapy, pain measurements, placebo eects,
mindfulness-based stress reduction (MBSR), mindfulness-based cognitive therapy
(MBCT), meditation therapy
Introduction
Pain is a multidimensional phenomenon with a significant biopsychosocial dimension.
According to the International Association for the Study of Pain (IASP), pain is defined
as “an unpleasant sensory and emotional experience associated with, or resembling that
associated with, actual or potential damage” (Raja et al., 2020). The biopsychosocial
dimension of pain is fully recognized in the first note attached to the abovementioned pain
definition. It determines the individuality of the pain experience: “Pain is always a personal
experience that is influenced to varying degrees by biological, psychological, and social
factors” (Raja et al., 2020). This subjective response to pain is dynamically modulated by
complex interactions between sensory, cognitive, and affective factors (Price, 2000;Auvray
et al., 2010). Pain is challenging to treat, and chronic pain is considered a medical issue
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Lopes et al. 10.3389/fnint.2024.1432270
(Turk, 2002;Cohen et al., 2021;Knopp-Sihota et al., 2022). Pain
treatment is also an ethical issue since many patients fail to receive
adequate pain relief (Hall and Boswell, 2009;Gatchel et al., 2014).
Each pain patient is unique, and it is crucial to consider the
individual behind the pain. The principles of autonomy, non-
maleficence, beneficence, and justice are necessary to assist patients
and their families in pain management (Swenson, 2002;Reeves
and Jones, 2022). The use of cognitive-behavioral approaches in
pain management is growing, as these methods help improve the
patient’s relationship with a painful experience (Moisset et al., 2020;
Brandel et al., 2022;Yang et al., 2022).
Among cognitive-behavioral approaches, mindfulness-based
interventions (MBIs) are increasingly used (Baminiwatta and
Solangaarachchi, 2021). By defining mindfulness as the “awareness
that arises through paying attention, on purpose, in the present
moment, non-judgmentally,” Kabat-Zinn laid the foundation for
using MBIs in pain management and other medical areas (Kabat-
Zinn, 1982;Ludwig and Kabat-Zinn, 2008). Despite numerous
studies on the efficacy of MBIs in pain management, the extent
of their efficacy varies (Mcclintock et al., 2019;Shires et al.,
2020;Schmidt and Pilat, 2023). Notably, the efficacy of MBIs is
predominantly observed in reducing the aversive component of
pain rather than its sensory component (Jinich-Diamant et al.,
2020).
The variability in the efficacy of MBIs for pain can be attributed
to some of the challenges in their design (Leca and Tavares, 2022;
Cardle et al., 2023). The challenges include the lack of active
controls in MBIs, the need for better reporting of important
parameters such as the background of the meditation instructors,
the wide diversity of evaluated outcome domains, and the lack of
agreement on the operational definition of MBIs (session lengths,
number of sessions, frequency of sessions, and duration of the
intervention). One significant issue to consider in MBIs for pain
management is the placebo effect. Several studies show that the
efficacy of MBIs in pain management is lower when active controls
(i.e., an experimental group that controls for the placebo effect)
are used instead of passive controls (Goldberg et al., 2018;Shires
et al., 2020;Hohenschurz-Schmidt et al., 2023a,b). Furthermore,
the more specifically the active control is matched to the treatment
(i.e., the better it controls for the placebo effect), the smaller the
observed efficacy of MBIs is.
Placebo effects in pain responses are well-established (Coleshill
et al., 2018;Bingel, 2020;Rossettini et al., 2020;Van Lennep et al.,
2021). The term “placebo” originates from the Latin word “placere,”
which means “to please” (Schedlowski et al., 2015;Meissner and
Linde, 2018). The placebo effect involves the improvement of
symptoms or physiological conditions following an inert treatment.
It can be influenced by various factors, such as the natural
progression of a disease, symptom fluctuations, response biases,
the effects of co-interventions, and statistical phenomena. The
placebo response, defined as the “outcome caused by a placebo
manipulation,” depends on emotional and cognitive aspects.
Factors such as patient expectations, the quality of the doctor–
patient relationship, and other variables were shown to significantly
affect the placebo response (Schedlowski et al., 2015;Meissner and
Linde, 2018).
The importance of the placebo effect is well-recognized,
and its effects may be manipulated. It is well-established that
the placebo effect may confound the specific actions of active
compounds in pharmacologic studies (Scott et al., 2008). In clinical
pharmacological trials, the placebo arm groups and the interference
of non-specific effects are considered to fully evaluate the specific
effect of a new treatment (Pollo and Benedetti, 2009;Enck et al.,
2013). Recent research has advanced our understanding of the
neural mechanisms underlying placebo effects. The potential to
harness the placebo effect (Scott et al., 2008;Bingel et al., 2011) to
influence therapy outcomes and benefit patients is currently being
considered and discussed (Pollo and Benedetti, 2009;Enck et al.,
2013).
Pain is modulated by a network of brain areas known
as the supraspinal endogenous pain modulatory system. The
understanding of this system has evolved considerably to include
the dynamic interaction of pain with other interconnected
dimensions, such as emotion and cognition (Tracey and Mantyh,
2007;Heinricher et al., 2009). Furthermore, the dynamic balance
between inhibition and facilitation of top-down descending
modulation is recognized, and an imbalance toward facilitation
is considered to contribute to chronic pain (Tracey and Mantyh,
2007).
Among the brain areas of the endogenous pain modulatory
system, the periaqueductal gray (PAG) plays a key role in top-
down modulation by conveying most of the input from higher
brain areas, such as the prefrontal cortex (PFC), which is involved
in cognitive and executive control, and the amygdala, which is
involved in emotional responses (Martins and Tavares, 2017;Ng
et al., 2018). There are, however, direct effects on the spinal cord,
such as direct cortico-spinal pathways from the anterior cingulate
cortex (ACC), which facilitate the transmission of nociceptive
information (Chen et al., 2018).
Regarding the neurobiological networks that may underlie
the effects of MBIs on pain, a reduction in the activity of
areas involved in emotional reactions to pain, such as the
amygdala, may account for the reduction in aversion to the
noxious event (Zeidan and Vago, 2016). Regarding the placebo
effect, a neural network between the rostral ACC (rACC) and
brain stem areas, including the PAG, has been proposed to
account for placebo responses, showing similar activation patterns
during opioid analgesia (Petrovic et al., 2002). In addition to
the cingulofrontal brain regions, placebo analgesia is associated
with activation in other areas, such as the PAG, hypothalamus,
and amygdala.
The unique role of the ACC and its connections with the
emotional components of the limbic system and the cognitive PFC
is interesting due to the emotional and cognitive components of
the placebo effect. The PFC also plays an important role in this
network (Wager et al., 2004;Lui et al., 2010). Neuroimaging studies
have also shown a negative correlation between the magnitude of
placebo analgesia and the activation of the rACC, contralateral
insula, primary somatosensory cortex (S1), and thalamus (Wager
et al., 2004;Eippert et al., 2009).
Regarding expectations and their relation to the placebo
effect, the manipulation of expectations modulates pain through
endogenous opioidergic release (Case et al., 2021). In contrast,
conditioned placebo responses to pain do not appear to be
mediated by opioids (Amanzio and Benedetti, 1999). Interestingly,
reappraisal-based manipulations based on mindfulness are
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postulated to reduce pain through non-opioid mechanisms
(Zeidan et al., 2016;May et al., 2018;Wells et al., 2020).
Based on the abovementioned literature, we hypothesize that
the efficacy of MBIs in pain may be affected by placebo effects and
that the expectations of the participants may affect the outcome
of these interventions. Therefore, it is important to systematically
evaluate the literature to understand the mechanisms specific to
mindfulness that are not activated by a placebo intervention. To
this end, we conducted a systematic review to assess the evidence
for the evaluation of placebo effects in MBIs for pain and to analyze
if the expectations of the participants were considered in the studies
and if the involvement of opioid mechanisms was examined.
Materials and methods
The present research was conducted in accordance with
the Cochrane recommendations on systematic reviews and
adhered to the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) guidelines (Moher
et al., 2009;Higgins et al., 2011). The review protocol was
not preregistered in the International Prospective Register of
Systematic Reviews (PROSPERO).
For this project, three different databases, namely Pubmed,
Web of Science, and SCOPUS, were searched until May 2024. The
search was performed between 1 November and 30 November 2022
and updated on 30 May 2024. For the present systematic review, the
population, intervention, comparison, outcomes (PICO) question
was: “What is the evidence for the evaluation of placebo effects of
participants in MBI studies for pain?” No a priori distinctions were
made between the types of MBI interventions or the duration of
pain (acute or chronic).
The following MeSH terms were used in all the databases:
“placebo,” AND “pain,” AND “mindfulness,” with no restrictions
applied to the results. Initially, we included all articles that met our
search criteria. All the articles were organized in a table specifying
the name, author, and study design. Two authors (AL and IT)
examined the titles and abstracts of the selected studies. Review
articles were excluded, and all the original articles were considered
eligible for further analysis.
The full text of these original articles was extracted, and
after analysis by both authors, it was consensually agreed that an
additional six articles should be discarded for not meeting the
inclusion criteria (studies using MBIs for pain). In the end, we were
left with a total of 19 articles. For each of these articles, both authors
analyzed the population (the inclusion and exclusion criteria),
experimental design, the type of pain studied, the type and duration
of the MBIs, the characteristics of the instructors providing the
interventions, the communication between the research team and
participants, participant expectations (if they were considered), and
the study of placebo and outcomes. The selection process followed
the recent PRISMA guidelines (Page et al., 2021;Figure 1).
To assess the risk of bias, both authors used the Cochrane
Risk of Bias Tool for randomized controlled trials (Higgins et al.,
FIGURE 1
PRISMA 2020 flow diagram for new systematic reviews which included searches of databases and registers only. *Means registered databases.
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2011) and the Newcastle-Ottawa Scale for non-randomized studies
(Wells et al., 2021). The Cochrane Risk of Bias Tool for Randomized
Controlled Trials evaluates six different criteria. An article was
considered to have a low risk of bias if all criteria were met, a
moderate risk of bias if one criterion was missing or two criteria
were not followed, and a high risk of bias if two or more criteria
were missing.
The Newcastle-Ottawa Scale evaluates eight different criteria,
which are grouped into three categories: selection (a maximum
of four stars), comparison (a maximum of two stars), and
result/exposition (a maximum of three stars). For classifying the
articles, an article was considered to have a low risk of bias if it
had three or four stars in the selection category. It was considered
to have a moderate risk of bias if it had two stars in the selection
category, one or two stars in the comparison category, and two
or three stars in the result/exposition category. An article was
considered to have a high risk of bias if it had zero or one star in
the selection category, zero stars in the comparison category, and
zero or one star in the result/exposition category.
Results
A total of 272 articles were collected from all databases,
namely 59 from PubMed, 67 from Web of Science, and 116 from
SCOPUS databases. After removing duplicates, we were left with
140 different results. After screening the titles and abstracts of
these studies, only original articles were considered eligible, and all
reviews were excluded, resulting in a total of 25 articles proceeding
to the inclusion phase. Both authors analyzed the full text of these
25 studies and agreed to eliminate six additional articles for not
meeting the inclusion criteria: two articles did not focus on the
study of pain and three did not use an MBI. In the end, we were
left with a total of 19 articles.
For each of these 19 articles, both authors analyzed the
population of participants concerning the inclusion and exclusion
criteria, specifically regarding their previous experience in
meditation and mindfulness, as it could affect the answer to the
main question of our study. We also extracted data regarding
the experimental design, the type of pain studied, the type and
duration of MBIs, the experience and possible conflicts of interest
of the instructors guiding the MBIs, the communication between
the research team and the participants, whether the expectations of
the participants were considered, and the study of placebo effects.
The main outcomes analyzed were the effects on pain, both in
sensory intensity and unpleasantness (Table 1). Table 1 presents
the results of the 19 analyzed studies concerning (1) the effects
of MBIs on pain; (2) the involvement of endogenous opioids in
the effects of MBIs on pain; and (3) participant expectations and
analysis of placebo effects.
Regarding the effects of MBIs on pain, it should be noted
that the studies evaluated mostly acute pain (i.e., experimentally
induced pain), with 10 out of the 19 analyzed studies focusing
on this type of pain. Among these studies, noxious heat was
the predominant stimulus applied in seven studies, followed by
cold (one study), ischemic stimulation (one study), and electric
stimulation (one study). For chronic pain, several types of
pain were analyzed, with a predominance of migraine/headache
(three studies). Other types of chronic pain studied included
musculoskeletal pain, such as arthritis (two studies), fibromyalgia
(one study), low back pain (one study), diabetic neuropathy (one
study), and diverse types of chronic pain (one study).
Information regarding the duration of chronic pain and the
occurrence of pain co-morbidities, such as cognitive deficits
and emotional imbalances, could not always be retrieved from
the analyzed papers. A randomized controlled trial (Westenberg
et al., 2018) studied the effect of a brief 60-s mindfulness video
exercise on musculoskeletal pain in upper extremity patients and
concluded that there were improvements in momentary pain,
anxiety, depression, and anger. Three studies focused on the
effect of mindfulness therapies on headaches. One of them was
conducted in a population of adolescents using adaptations of
MBSR and MBCT and revealed that the intervention resulted
in reduced headache frequency and medication intake, disability,
trait anxiety, symptoms of depression, and catastrophizing (Grazzi
et al., 2021). The other two studies were conducted with adults
and demonstrated that mindfulness reduced headache frequency,
headache-related disability (Seminowicz et al., 2020), and decreased
pain severity (Namjoo et al., 2019).
Mindfulness-based interventions have been proven to improve
the quality of life in patients with painful diabetic neuropathy,
with better results observed when combined with vitamin D
supplementation (Davoudi et al., 2021). Additionally, they reduced
pain in rheumatoid arthritis patients, with greater benefits observed
in patients with recurrent depression (Zautra et al., 2008).
However, when focusing on a population of fibromyalgia patients,
the analyzed study (Schmidt et al., 2011) did not support the
improvement of quality of life in patients receiving MBSR. Overall,
regarding the net effects of MBIs, the results indicate the benefits of
MBIs in acute and chronic pain.
Regarding the neurobiological mechanisms involved in MBIs’
effects on pain, particularly concerning endogenous opioids, the
majority of the results indicate that mindfulness meditation pain
relief is not mediated by endogenous opioids (Zeidan et al., 2016;
Esch et al., 2017;May et al., 2018;Wells et al., 2020). However, this
finding was not supported by another study (Sharon et al., 2016),
which concluded that the effects of mindfulness meditation on pain
relief were mediated by endogenous opioids. Notably, the result of
the latter study was based on a small population size (n=14). The
remaining studies did not analyze opioid involvement in MBIs for
pain in detail. Collectively, the analyzed literature predominantly
suggests that the effects of MBIs on pain are not mediated by
endogenous opioids.
Finally, regarding participants’ expectations and the analysis
of the placebo effect, the analyzed literature presented a variety
of results. Information about collecting participants’ expectations
concerning the pain relief they could receive from MBIs was sparse.
Five studies clearly evaluated the expectations of the participants.
The studies of the Davies group (Davies et al., 2021,2022,2023)
analyzed in detail the initial expectations of the participants,
including manipulating expectations to test the effects of the MBIs
(Davies et al., 2022). One of the studies (Vencatachellum et al.,
2021) hypothesized that mindfulness could reduce cue-induced
hypoalgesia and hyperalgesia and found evidence supporting the
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 1 Summary of the main findings of the analyzed studies (in alphabetic order).
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Case et al. (2021)
Study type:
secondary
analysis of
previous work
Population: 78 (39 ♂/39
♀)
Mean age: 27 ±7
Experimental groups:
Meditation +naloxone
Control +naloxone
Meditation +saline
Control +saline
Previous experience in
MBI: Not referred
Duration: Acute
Modality/type:
Noxious heat
(35–49◦C)
Type: Mindfulness-based
mental training
Duration: 4 sessions of
20 min
Instructors:
- Formation/experience:
not referred
- Conflicts of
interest/Disclosure of
Instructors/Authors:
Referred: none
Referred:
- Participants were told that: “the study
would assess whether meditation was
associated with the release of naturally
occurring opiates”
- They would receive intravenous
administration of saline or naloxone, a
relatively safe drug that blocks the
transmission of opioid activity
Evaluated: Yes
Remarks: In a scale of
0–10 how much do you
expect that meditation
will be effective in
reducing your pain?
Placebo of the MBI
intervention: Placebo
saline for naloxone
- MBI lowered pain during
saline and naloxone infusion
- Higher expected pain- relief
from MBI predicted lower pain
intensity
- Relation between meditation-
related expectations and
reduction of pain intensity
during naloxone infusion, but
not saline
- Expectations for book-
listening based analgesia did
not significantly predict pain
changes during saline or
naloxone infusion in the
control group.
Davies et al.
(2021)
Study type: RCT
Population: 93 (34 ♂/59
♀)
Mean age: 21 ±9
Experimental groups:
- Mindfulness
- Sham mindfulness
- No treatment
Inclusion criteria: Fluent
in English Pain-free
(<3/10)
- Meditation naïve Not
pregnant/breastfeeding
- Not under analgesic or
psychotropic medication.
Previous experience in
MBI/meditation:
Meditation naïve
Duration: Acute
Modality/type: Heat
Type: “Mindfulness of
Breath and Body”
(MBCT adaptation for
chronic pain) Duration:
Four sessions of 20-min
training in home practice
of an audio recording
Instructors:
Formation/experience:
not referred
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred: None
Referred:
Informed consent: Yes; No details
provided
Evaluated: Yes
Remarks: At the
beginning of the project
“no suggestion was made
regarding mindfulness
being effective for pain in
any study materials or
procedures, including the
meditation training” and
“How effective do you
think mindfulness is for
reducing pain?” At the
end of the project “Do
you think you were
practicing a guided
mindfulness meditation?”
Placebo of the MBI
intervention: Sham-
intervention group
delivered as MBI
- Sham MBI produced
equivalent credibility ratings
and expectations of
improvement as MBI, but did
not influence mindfulness-
related processes.
- MBI increased “observing”
(but none of the other four
mindfulness facets) relative to
no treatment, but not sham.
- MBI and sham moderately
increased pain tolerance
relative to no treatment, with
no difference between
mindfulness and sham.
- No effects in pain threshold.
- Neither MBI nor sham
reduced pain intensity or
unpleasantness relative to no
treatment, although MBI
reduced pain unpleasantness
relative to sham.
(Continued)
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TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Davies et al.
(2022)
Study type: RCT
Population: 153 (42
♂/111 ♀)
Mean age: 22 ±93
Experimental groups:
- Mindfulness with
expectancy (mindfulness
treatment and told
mindfulness);
- Mindfulness without
expectancy (mindfulness
treatment and told sham);
- SHAM+(sham
treatment and told
mindfulness)
- SHAM- (sham
treatment and told sham),
with an additional
comparison against a no
treatment control group.
Inclusion criteria:
- Fluent in English
- Pain free
- Not pregnant,
breastfeeding
- Not taking analgesic or
psychotropic medications.
Previous experience in
MBI/Meditation:
Mindfulness naïve
Duration: Acute
Modality/type:
Noxious heat
Type: Focused attention
mindfulness (breath and
body)
Duration/place: Six daily
sessions lasting 20-min
of audio guided training;
first and last session in
the lab and the
remaining home
Instructors:
- Formation/experience:
Not referred
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred: none
Referred:
- Several moments of communication
with the participants to determine
expectations.
- Instructions displayed on the
computer screen (and reiterated in a
short audio introduction) revealed the
group allocation to the participant (i.e.,
mindfulness, sham mindfulness, or no
treatment, as per cover story) without
the researcher’s knowledge (to
maintain blinding).
Informed consent: Yes; Details
provided
Evaluated: Yes The study
evaluates expectancy so
that it can be manipulated
to test the effect of
intervention.
Remarks: Participants
were asked in several
moments questions like
“How effective do you
think mindfulness
meditation is for reducing
pain?” and “How effective
do you think your
training will be for
reducing pain?”
Placebo of the MBI
intervention: Balanced
placebo designs
allowing for
manipulation of both
treatment and
instruction
(expectation)
- MBI improved pain
outcomes (unpleasantness,
intensity, and tolerance) in
comparison to control.
- The instruction manipulation
increased expectation for pain
relief in those told mindfulness
relative to those told sham.
- There were no main effects or
interactions of treatment or
instruction on pain outcomes.
- Irrespective of actual
intervention received, the
belief of receiving mindfulness
predicted increased pain
threshold and tolerance, with
expectancy fully mediating the
effect on pain tolerance.
(Continued)
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TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Davies et al.
(2023)
Study type: RCT
Population: 169 (28
♂/138 ♀) males; 3 other
Mean age: 32 ±8
Experimental groups:
- Mindfulness of
Breath/Body
- Specific sham
mindfulness
- General sham
mindfulness
- Audiobook control
Inclusion criteria:
- 18 years of age or older,
- Understand English,
- Chronic or recurrent
pain as clinical guidelines
Previous experience in
MBI/Meditation: Not
referred
Duration: Chronic
pain/recurrent pain
Modality/type:
Diverse (arthritis,
muscle pain,
headache,
menstrual,
neuropathic, other)
Type: Mindfulness of
Breath and Body
Duration: one 20-min
session
Instructors: -
Formation/experience:
experienced meditation
instructor
- Conflicts of
interest/Disclosure of
Instructors/Authors:
Referred: “The authors
have no conflicts of
interest to declare.” After
setup, the research team
had no involvement in
the running of the RCT,
which was entirely
automate (“the study was
ostensibly double
blind”).
Referred: Yes
- Participants were asked to
numerically rate the current intensity
and unpleasantness of pain.
- The analogy of listening to a song on
the radio was used to help participants
differentiate between intensity and
unpleasantness.
Informed consent: Yes
Evaluated: Yes
Remarks: “We assessed
pre-to-post changes in
placebo-related (response
expectancy and hope)
processes to assess
potential differential
effects of mindfulness,
specific sham, and general
sham relative to
audiobook control.”
Expectancy was assessed
at baseline by asking
participants: “How
effective do you think
mindfulness meditation is
for reducing pain?”
Placebo of the MBI
intervention:
- Specific sham
mindfulness: condition
developed and validated
to explicitly control for
non-specific factors
present in the
“Mindfulness of Breath
and Body”;
characterized by a
facilitator voice,
attention paid to the
intervention, body
posture and
instructions designed to
give the meditator the
sense that they were
practicing a guided
meditation, except for
instructions that
explicitly or implicitly
suggested training
attention on present
moment experience or
brought mindfulness
metacognitive qualities
to attention
General sham
mindfulness: Did not
include any
mindfulness
instructions.
- Mindfulness not superior to
sham in reduction of pain
intensity/unpleasantness.
- Mindfulness and sham
reduced pain unpleasantness
(but not pain intensity) relative
to audiobook control, with
expectancy most strongly
associated with this effect.
- Treatment expectancy
associated with decreases in
pain intensity and
unpleasantness after
mindfulness and sham
training.
- Specific and general sham
with equivalent expectancy and
credibility ratings to each other
and the mindfulness
intervention (suggesting that
all three interventions were
likely to engage placebo-related
processes equally)
- Mindfulness and sham
equally reduced pain
catastrophizing relative to
audiobook control
- No differences in pain
reappraisal between
mindfulness, shams, and
audiobook control.
(Continued)
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Davoudi et al.
(2021)
Study type: RCT
Population: 225 (133
♂/92♀)
Mean age: 56 ±25
Experimental groups:
- Mindfulness and
placebo
- Placebo
- Mindfulness
- Vitamin D
- Mindfulness +Vitamin
D
Inclusion criteria: Patients
referred to the hospital.
- Lack of major
co-morbid disease
- Age of 20–70 years
Willingness to participate
in studying
- Vitamin D insufficiency
or deficiency
Previous experience in
MBI: Not referred
Duration: Chronic
Modality/type:
Diabetic
neuropathy
Type: modified
mindfulness manual
based on pain relief
protocols
Duration: 12 weeks
(90 min per session)
Instructors:
- Formation/experience:
trained psychotherapist
- Conflicts of
interest/Disclosure of
Instructors/Authors:
Referred: none
Referred: They were blinded about
study aims and other groups’ existence
(VDs and other mindfulness groups).
Informed consent: Not referred
Evaluated: No
Remarks: Not referred
Placebo of the MBI
intervention: similar
drops in shape (without
any VD) and duration.
- Improvement of QOL in all
groups except the “placebo
only” group for outcome
variables.
- There was no difference
between VD and MBI groups
(within and not combined with
placebo) in improvement of
QOL
- “VD +MBI” has a greater
improvement in QOL rather
than VD and mindfulness
groups.
- Reduction in pain disability
and pain severity in all groups
except “placebo.” No difference
between MBI and VD groups
to reduce pain disability and
pain severity. Yet, the “vitamin
D+mindfulness” group
showed the higher
improvement.
(Continued)
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TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Esch et al. (2017)
Study type: RCT
Population: 31 (8 ♂/24♀)
Mean age: 27 ±8
Experimental groups:
- Passive control
condition (no
intervention)
- Combined
breathing/mindfulness
meditation technique
Inclusion criteria:
- At least 18 years old
Language proficient
- No visual impairments
Previous experience in
MBI: Meditation naïve
volunteers
Duration: Acute
Modality/type:
Ischemic arm pain
(tourniquet test)
Type: combined
breathing/mindfulness
meditation technique
(bodyscan, attention to
breath (ATB), attention
to senses (ATS), open
awareness/attention to
experience (ATE), and
walking
meditation—with
focused breath awareness
as a steady anchor)
Duration: daily group
sessions of 1.5 h each
Instructors:
- Formation/experience:
The trainer (TE) had 20
years of meditation
experience, and is a
professional
meditation/mindfulness
teacher, and researcher
in the field.
- Conflicts of
interest/disclosure of
Instructors/Authors:
none
The topic of pain (e.g., pain awareness
or pain perception) was intentionally
and carefully avoided in this course.
Participants were informed about their
individual group
assignment—intervention or
control—(to get to know whether they
would be required to show-up for
intervention training) after the
completion of assessments on day 2 by
a person otherwise not interacting with
the participants.
Informed consent: Yes
Evaluated: No
Remarks: It was measured
the self-attributed
minfulness by the
Freiburg Mindfulness
Inventory
Placebo of the MBI
intervention: Placebo
saline for naloxone
- The MBI group meditation
group produced fewer errors in
ANT (Attention Network Test)
- Increases in pain tolerance
occurred in both groups
(accentuated in control), and
correlated with reported
mindfulness
- Naloxone showed a trend to
decrease pain tolerance in both
groups.
Grazzi et al.
(2021)
Study type: Open
Label Study
Population: 37 (2 ♂/35 ♀)
Mean age: 15 ±2
Experimental groups:
Participants completed 6
weekly group sessions of
guided meditation, and
one booster session 15
days later.
Inclusion criteria:
Adolescents (12–18)
chronic or high-frequency
migraine without aura.
Previous experience in
MBI: meditation naive
Duration: Chronic
Modality/type:
Migraine
Type: Adaptation of
MBSR and MBCT
programs, by shortening
these programs
Duration/place: 6 weeks
group sessions with 1 h
duration followed by one
booster session 15 days
after
Referred: Not explicitly mentioned.
Informed consent: Yes: for adolescents
and their parents; details not available
Evaluated: No Placebo of the MBI
intervention: Not
performed but authors
refer as a limitation
intrinsic to an
open-label study
- MBI decreases headache
frequency MBI had effects on
medication intake, disability,
trait anxiety, symptoms of
depression and catastrophizing
(Continued)
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TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Khatib et al.
(2024)
Study type: RCT
Population: 59 (29 ♂/30
♀)
Mean age: 46
Experimental groups:
- Mindfulness
- Sham
mindfulness-meditation
Inclusion criteria:
- Not positive for opioids
- Not pregnant
- Meditation naive
- Responsive to the
straight leg-raise test,
- Not having back surgery
within a year of the
enrollment
- Not concurrently
enrolled in other
experiments
- Not initiating new pain
therapies during the study
period.
Previous experience in
MBI/meditation:
Mindfulness naive
Duration: Chronic
Modality/type: Low
back pain
Type: Mindfulness based
mental training
Duration: Four 20-min
sessions
Instructors:
- Formation/experience:
certified meditation
instructors.
- Conflicts of
interest/Disclosure of
Instructors/Authors:
Referred: Drug
assignment blinded to
patients, nurses, and
experimenters. Only the
physicians, pharmacist,
and coordinator aware of
drug assignment.
Participants were
compensated $400 for
study completion.
Referred: Yes
- In Straight leg-raise 1
(non-meditation rest), patients were
instructed to “rest with your eyes
closed” and after 7 min, pain ratings
were collected.
- In pre-intervention bolus control,
patients were instructed to “continue
resting with your eyes closed” (8 min).
- In all 4 mindfulness sessions,
instructions acknowledging arising
thoughts, feelings, and/or emotions,
that such sensations and emotions were
“momentary” and “fleeting,” and to
“return their attention back to the
breath” whenever such discursive
events occurred. During training day 4,
participants were asked to practice
while lying in the supine position and
wearing a face mask to emulate the
conditions in the post-intervention
testing sessions.
- During each sham
mindfulness-meditation training
session, the participants were told,
approximately every 2–3 min, to “take
deep breaths as we sit in meditation.”
Evaluated: No
Remarks: Not referred
Placebo of the MBI
intervention: Sham-
mindfulness meditation
(train individuals to
“take slow, deep
breaths” in a meditative
posture but omits the
mindfulness-specific
instructions
non-reactive attention
to breath sensations—
hypothesized to mediate
pain relief); Placebo
saline for naloxone
- After the interventions,
mindfulness and sham
mindfulness-meditation
effectively attenuated induced
pain.
- Mindfulness-meditation with
lower pain before and after the
straight leg-raise test when
resting and during meditation
when compared to the sham
mindfulness-meditation group.
- Mindfulness and sham
mindfulness-meditation
associated with significant
reductions in back pain during
saline and naloxone infusion
when compared to rest
(non-meditation).
- Meditation directly reduces
evoked chronic pain through
non-opioidergic processes
- Mindfulness group with
lower straight leg-raise induced
pain than the sham
mindfulness-meditation group
during rest (non-meditation)
and meditation.
- Mindfulness and sham
mindfulness-meditation
training was also associated
with significantly lower Brief
Pain Inventory severity and
interference scores
- Mindfulness and sham
mindfulness-meditation
training associated with
significant improvements in
pain interference and pain
catastrophizing after 80-min of
mental training
(Continued)
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TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
May et al. (2018)
Study type: RCT
Population: 32 (18 ♂/14
♀)
Mean age: 52 ±52
Experimental groups:
- Saline
- Naloxone
Inclusion criteria:
- Pain-free adults with
established meditation
practice
- From the local
community
Previous experience in
MBI/meditation:
Experienced meditators
Duration: Acute
Modality/type:
Electric current
5 Hz
Type: Open
Monitoring/Awareness
but the background of
the experienced
meditators was very
diverse.
Duration/place: 10 min
prior to nociceptive
stimulation Instructors:
- Formation/experience:
Not referred
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred in detail
Referred: The researcher described the
protocol taking into account the
specificities of the sessions and
participants gave their consent
Informed consent: Yes; in two different
moments; Details not available
Evaluated: Yes The
authors referred that “the
participants had a variety
of expectations of the
drug effect”.
Remarks:
- Participants were kept
blind as to the naloxone
or saline administration.
- They were subsequently
asked “in which session
they believed they
received naloxone” and
“in your opinion what
does naloxone do”
Placebo of the MBI: No;
the placebo effect
focuses on
naloxone/saline
administration
- MBI induced analgesia
(lowered pain intensity and
pain unpleasantness)
- Naloxone increased
meditation-induced analgesia
(lower pain intensity and pain
unpleasantness)
Namjoo et al.
(2019)
Study type: RCT
Population: 85 (29 ♂/56
♀)
Mean age: 36 ±7
Experimental groups:
- MBCT
- Attention Placebo
Control
Inclusion criteria:
->19 years
- Headache experience at
least
- 3 days/month and for >
3 months) due to a
primary headache
- Reading and writing
skills to understand and
complete worksheets
Previous experience in
MBI/meditation: Not
referred (just “engaging in
other psychotherapies for
pain condition”)
Duration: Chronic
Modality/type:
Headache
Type: MBCT (the first
half of the protocol
focused on the
preferment of awareness
of patients about mind
default mode; in the
second half of treatment,
enhanced awareness
converted to automatic
skills and patients learn
to choose intentionally
to respond to their
experiences rather than
to react.
Duration 8-weekly 2 h
group program
Instructors:
- Formation/experience:
Superior in MBCT
fibromyalgia patients.
- Conflicts of
interest/Disclosure of
Instructors/Authors:
Referred: none
Referred: No
Informed consent: Yes
Evaluated: No
Remarks: Not referred
Placebo of the MBI
intervention: Attention
Placebo Control −8
weekly 2 h sessions;
participants received
attention and therapist’s
empathy and
participated in group
discussion.
- Change of scores across the
two groups over time (for pain
severity and for pain
interference (pleasing result for
researchers who claim that
MBI can affect pain
perception)
- MBI resulted in a higher rate
of pain openness and a lower
rate of pain focus compared to
the APC group from baseline
to follow-up.
- MBI resulted in a higher rate
of pain distancing compared to
the APC group from baseline
to post-test and the reappraisal
scores decreased in the
follow-up—MBI was
ineffective and could not make
any changes on pain diversion
(Continued)
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TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Schmidt et al.
(2011)
Study type: RCT
Population: 177 (0 ♂/177
♀)
Mean age: 52 ±5
Experimental groups:
- MBSR
- Active control procedure
(o que é?) Wait list
Inclusion criteria:
- 18–70 years of age
- Currently with
fibromyalgia diagnosis
(criteria of the American
- College of
Rheumatology)
- Command of the
German language
- Motivation to
participate
Previous experience in
MBI/meditation: Not
referred
Duration: Chronic
Modality/type:
Fibromyalgia
Type: MBSR
(mindfulness meditation
and mindful yoga
exercises)
Duration: 8-week group
program (one 2.5-h
session every week, and
an additional 7-h all-day
session on a weekend
day.) Instructors:
- Formation/experience:
at least 7 years of
previous experience
teaching MBSR
- Conflicts of
interest/Disclosure of
Instructors/Authors:
Referred: none
Referred: “Informational brochures
were provided that briefly described
the 2 interventions as alternative
behavioral treatments potentially
capable of enhancing the wellbeing in
fibromyalgia patients.
- No suggestion was made about the
superiority of either treatment.”
- “Patients in the intervention arms
were told that 2 new innovative
treatments were to be compared, one
based on the concept of mindfulness
(entailing meditation and yoga lessons,
as well as homework), and the other
based on health support techniques
(entailing relaxation and stretching
exercises, as well as homework). The
active control group was referred to as
the relaxation group. All patients
participating in one of the 2 active
treatment arms were also offered
participation in their treatment of
choice after completion of the trial.”
Informed consent: Yes
Evaluated: Yes
Remarks: “Pre- and
post-intervention 1-h
personal interviews were
conducted by each
instructor to establish
rapport and to help
patients formulate
realistic individual goals
for the intervention.”
Placebo of the MBI
intervention: The active
control is considered
the placebo.
8-week group of size
and weekly format
similar to that of the
MBSR program taught
by a single instructor;
Equivalent amounts of
social support and
weekly topical
educational discussions;
use of Jacobson
Progressive Muscle
Relaxation training
(PMR), and
fibromyalgia- specific
gentle stretching
exercises; homework
assignments were
similar in duration and
intensity to those in the
MBSR group; patients
received compact discs
(CDs) with instructions
for daily exercises
- No significant differences
between groups on primary
outcome (health related quality
of life), but patients overall
improved in HRQoL at
short-term follow-up. Only
MBI manifested a significant
pre-to-post- intervention
improvement in HRQoL
- Multivariate analysis of
secondary measures
(disorder-specific quality of
life, depression, pain, anxiety,
somatic complaints, and a
proposed index of
mindfulness) indicated modest
benefits for MBSR patients.
MBSR yielded significant pre-
to-post-intervention
improvements in 6 of 8
secondary outcome variables,
the active control in 3, and the
wait list in 2.
Seminowicz et al.
(2020)
Study type: RCT
Population: 98 (9 ♂/89 ♀)
Mean age: 36
Experimental groups:
MBSR Stress management
for headache (o que é?)
Inclusion criteria:
- 18–65 years of age
- Diagnosis of migraine
(International
Classification of
Headache Disorders for
migraine with/without
aura)
-≥1 year history of a
migraine diagnosis
Previous experience in
MBI/meditation:
Meditation naive
Duration: Chronic
Modality/type:
Migraine
Type: MBSR vs. stress
management (active
control)
Duration/Place: 12
group sessions over 4
months, including 8
weekly sessions followed
by 4 biweekly sessions.
Instructors:
- Formation/experience:
Two experienced,
certified instructors (10
and 40 years of
meditation experience)
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred: none
Referred: Not explicitly mentioned.
Informed consent: Yes; details not
available
Evaluated: No
Remarks: Authors state
that the study accounts
for the influence of
expectations and
non-specific effects of
intervention but it is not
mentioned how the
expectations were
evaluated
Placebo of the MBI
intervention: The active
control is considered
the placebo. This
intervention included
12 sessions over 4
months with on didactic
content about the role
of stress and other
triggers in headaches in
a similar format of the
intervention group,
minus the retreat.
- MBI decreased headache and
migraine frequency and
intensity
- MBI decreased
headache-related disability, as
well as yielded a higher
treatment response rate, in
comparison to the active
control
(Continued)
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TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Sharon et al.
(2016)
Study type: RCT
Population: 14
Mean Age: not specified
Experimental groups:
- Intravenous naloxone
(0.1 mg/kg)
- Intravenous saline
Inclusion criteria: Same
meditation practice
Previous experience in
MBI/meditation:
Experienced meditators
Duration: Acute
Modality/type: Cold
stimulus (2–4◦C
water)
Type: Sitting
mindfulness meditation
with Shamatha or
Vipassana meditation
Duration/place: The
details of the
mindfulness practice
(duration, guidance,
groups) during the
intervention are unclear
Instructors:
- Formation/experience:
Not referred
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred: None
Referred: No details
Informed consent: Not referred
Evaluated: No
Remarks: Not referred
Placebo of the MBI
intervention: No; the
placebo effect focuses
on naloxone/saline
administration
- MBI and placebo reduced
pain and unpleasantness scores
- Naloxone did not reverse
MBI-induced induced
analgesia
- Positive correlation between
pain scores following naloxone
vs. placebo and participants’
mindfulness meditation
experience (reduced response
to placebo with increasing
experience).
Vencatachellum
et al. (2021)
Study type: Mixed
factorial design
Population: 62 (31 ♂/31
♀)
Mean age: 26 ±85
Experimental groups:
- Mindfulness-meditation
- Suppression (o que é?)
Inclusion criteria:
- 18 years or older
- Healthy
- Acute and chronic pain
free
Previous experience in
MBI/meditation: Not
referred
Duration: Acute
Modality/type:
Noxious heat
(43–49.5◦C)
Type: Mindfulness
meditation: open
awareness to sensations,
thoughts and emotions;
Audio recording
Suppression: Mentally
blocking out any arising
sensations, thoughts and
emotions and concealing
any external
manifestation of current
experiences
Duration: 10 min
Instructors:
- Formation/experience:
not referred
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred: none
Referred: A research staff member
provided instructions.
Informed consent: Yes; details not
available
Evaluated: No
Remarks: The authors
state that mindfulness
leads to a prioritization of
current sensory
information over previous
expectations, which were
not evaluated
Placebo of the MBI
intervention: Lack of
MBI reduction of
conditioned
hyperalgesia is
interpreted as absence
of placebo effect
- Pain Intensity: reduced
conditioned hypoalgesia in the
MBI group compared to the
suppression group
- Pain Unpleasantness: smaller
conditioned hypoalgesia
magnitudes in the MBI group
compared to the suppression
group
(Continued)
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Wells et al. (2020)
Study type: RCT
Population: 60 (30 ♂/30
♀)
Mean age: 27 ±7 years
old
Experimental groups:
- Mindfulness-meditation
(n=19)
- Sham-mindfulness
meditation
- Slow-paced breathing
Inclusion criteria:
- 18 years or older
Healthy
- Acute and chronic
pain-free
Previous experience in
MBI/meditation:
Meditation-naive
Duration: Acute
Modality/type:
Noxious heat
(49◦C)
Type: Mindfulness
meditation: non-reactive
attention to breath
sensations
Duration: 4 separate
sessions, 20 min each
Instructors:
- Formation/experience:
Certified Meditation
Teachers
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred in detail
Referred: Participants were informed of
their experimental group. Participants
of the sham group were lead to believe
“they were practicing mindfulness
meditation without instructions related
to mindfully attending to the breath in
a non-evaluative manner. Participants
were first told they were randomly
assigned to the mindfulness meditation
group.”
Informed consent: Yes; details not
available
Evaluated: No
Referred: The sham group
was intentionally lead to
belied that they were
practicing mindfulness
breathing
Placebo of the MBI
intervention: Sham-
mindfulness
meditation; Slow
Breathing; Saline
- MBI reduced pain
unpleasantness, but not pain
intensity, after naloxone or
saline infusion sessions when
compared to rest.
- Slow-paced breathing
reduced pain intensity and
unpleasantness ratings during
naloxone, but not saline
infusion.
- Sham-mindfulness
meditation reduced pain
unpleasantness during saline
infusion which was reversed by
naloxone.
- Sham-mindfulness did not
lower pain intensity.
- Self-reported “focusing on
the breath” is a feature
associated with the
mindfulness-meditation and
slow paced- breathing, but not
sham-mindfulness meditation.
(Continued)
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Westenberg et al.
(2018)
Study type: RCT
Population: 125 (63 ♂/62
♀)
Mean age: 55 ±15
Experimental groups:
- Mindfulness-based
video exercise
- Education pamphlet
Inclusion criteria:
Attending an
appointment with the
orthopedic
Previous experience in
MBI/meditation:
Meditation naive
Duration: Chronic
Modality/type:
Musculoskeletal
pain
Type: Visualization
practice of identifying
stress full
thoughts/feeling and
releasing with the breath
using a video support
Duration/place:
60-second mindfulness;
waiting room
Instructors:
- Formation/experience:
Background of the
instructors not referred
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred: none
Referred: Not explicitly mentioned.
Informed consent: Yes; details not
available
Evaluated: No
Remarks: Participants
were kept blind to the
intervention. They were
told that a comparison of
2 pain and stress
management
interventions was being
performed without
specifying the
intervention.
Placebo of the MBI
intervention: Attention
placebo control with an
educational pamphlet
about pain and stress
with the same duration
as MBI.
- MBI improved momentary
pain, anxiety, depression, and
anger patients in the waiting
room (high levels of
psychologic distress)
Zautra et al.
(2008)
Study type: RCT
Population: 144 (46 ♂/98
♀)
Mean age: 52 ±12
Experimental groups:
- Mindfulness-meditation
- Cognitive Behavioral
Therapy
- Education only
Inclusion criteria:
->or 18 years
- Self/Clinical- Diagnosis
of rheumatoid arthritis
Duration: Chronic
Modality/type:
Rheumatoid
arthritis
Type: Adaptation of
MBSR and MBCT to
chronic pain; examining
and promoting emotion
regulation and
adaptation in chronic
pain.
Duration: 8 weeks
program (MBSR/MBCT
format) but shorter (no
retreat; 10 min sitting
meditations).
Instructors:
Formation/experience:
not referred (doctoral-
level psychologist;
student level)
Referred: Not explicitly mentioned.
Informed consent: Yes; details not
available.
Evaluated: No
Remarks: The authors
state that “a direct
assessment of expectation
of improvement and
satisfaction with
treatment would be
import to assess
equivalence between
groups”
Placebo of the MBI
intervention: Education
group used as an
attention placebo
control
- MBI improved self- reported
pain, dependent on depression
history and pain assessment
method
- Patients with recurrent
depression benefited most
from MBI, in the affective
dimension and along with
physicians’ ratings of joint
tenderness
(Continued)
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Zeidan et al.
(2015)
Study type: RCT
Population: 75 (38 ♂/37
♀)
Mean age: 27 ±6
Experimental groups:
- Mindfulness meditation
Placebo conditioning
- Sham mindfulness
meditation
- Book-listening control
Inclusion criteria:
- Healthy
- Pain-free
- Right-handed volunteers
Without any prior
meditative experience
Previous experience in
MBI/meditation:
Meditation naïve
Duration: Acute
Modality/type:
Noxious heat
(35–49◦C)
4 days of Mindfulness
intervention vs. 4 days of
a placebo conditioning
regimen.
Type: Mindfulness-based
mental training: training
day 1: focus on the
breath sensations
occurring “at the tip of
the nose.” Training day
2: expansion of the focus
to the “full flow of the
breath,” including bodily
sensations training days
3 and 4: minimal
meditation instructions.
Duration: 4 sessions in 4
days; 20 min
Instructors:
- Formation/experience:
not referred
- Conflicts of
interest/Disclosures of
Instructors/Authors: Not
Referred
Referred: Participants were told that
they were participating in an
“experimental trial of a new
formulation of a topical, local
anesthetic being tested for its pain
reducing effects over time.” They were
told that the drug’s name is “lidocaine”
and that it “has been proven effective at
progressively reducing pain after
multiple applications in preliminary
studies at other universities.”
Informed consent: Yes; Details
provided
Evaluated: No
Remarks: The sham group
was intentionally lead to
belied that they were
practicing mindfulness
breathing
Placebo of the MBI
intervention: A
placebo- conditioned
regimen was designed
and tested
- All cognitive manipulations
(i.e., MBI, placebo
conditioning, sham MBI)
attenuated pain intensity and
unpleasantness ratings when
compared to rest and the
control condition.
- MBI produced greater pain
relief than placebo and sham
MBI by engaging different
brain mechanisms from those
of placebo and sham induced
analgesia
- The cognitive state of
mindfulness meditation
deactivated brain regions that
facilitate low-level sensory and
nociceptive processing
including the thalamus and
PAG compared with rest and
the main effects of placebo and
sham MBI.
- Compared with placebo
manipulation, MBI produced
greater activation in brain
regions that mediate the
cognitive control of pain.
Placebo produced greater
activation in several brain areas
in comparison to MBI.
- Sham MBI induce
overlapping activation of some
brain areas with MBI, and
deactivation of brain regions
associated with the default
mode network of the brain.
- Some brain areas presented
higher activation during sham
MBI compared with MBI,
whereas other had the opposite
response
(Continued)
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 1 (Continued)
References
Study type
Participants Pain MBI Communication research
team/participants
Participants
expectations
Analysis of
placebo eects
Outcomes
Zeidan et al.
(2016)
Study type: RCT
Population: 78 (39 ♂/39
♀)
Mean age: 27 ±7
Experimental groups:
- Meditation +naloxone
- Control +naloxone
- Meditation +saline
- Control +saline
Inclusion criteria:
- Healthy
- Pain-free
Meditation-naive
- Recruited from the local
community
Previous experience in
MBI/Meditation:
Meditation naïve
volunteers
Pain duration:
Acute
Pain modality:
Noxious heat
(35–49◦C)
Type: Mindfulness-based
mental training: training
day 1: focus on the
breath sensations
occurring “at the tip of
the nose.” Training day
2: expansion of the focus
to the “full flow of the
breath,” including bodily
sensations training days
3 and 4: minimal
meditation instructions
(no instructions for
practice tice outside
training sessions).
Duration: 4 sessions of
20 min.
Instructors:
- Formation/experience:
not referred
- Conflicts of
interest/Disclosures of
Instructors/Authors:
Referred in detail
Referred: Participants in the
meditation group were instructed to
“begin meditating until the end of the
experiment.” Participants in the
control group subjects were told to
“close your eyes and relax until the end
of the experiment”
Evaluated: No
Remarks: Not referred
Placebo of the MBI
intervention: Placebo
saline for naloxone
- MBI during saline infusion
significantly reduced pain
intensity and unpleasantness
ratings when compared to the
control+saline group.
- Naloxone infusion failed to
reverse meditation-induced
analgesia (pain intensity and
unpleasantness ratings)
- No significant differences in
pain intensity or pain
unpleasantness reductions
between the
meditation+naloxone and the
meditation+saline groups.
- MBI during naloxone
produced significantly greater
reductions in pain intensity
and unpleasantness than the
groups.
MBCT, Mindfulness based Cognitive Therapy; MBSR, Mindfulness-Based Stress Reduction; RCT, Randomized Controlled Trial.
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Lopes et al. 10.3389/fnint.2024.1432270
role of mindfulness in the reduction of cue-induced hyperalgesia.
Another study was a secondary analysis of a previous study (Zeidan
et al., 2016;Case et al., 2021) and demonstrated that participant
expectations about MBIs-induced effects on pain relief predicted
pain reductions, with this correlation being higher during opioid
antagonism (naloxone).
Some studies indicate that the placebo effect plays an important
role in MBIs’ pain relief and that expectancy is the strongest
predictor of decreases in pain unpleasantness and intensity, as well
as increases in pain tolerance (Davies et al., 2021,2022). One study
indicates that mindfulness meditation produces greater pain relief
than a placebo intervention (Zeidan et al., 2015) while engaging
different brain mechanisms. According to this study, mindfulness
is associated with the activation of brain areas responsible for the
cognitive modulation of pain, such as the ACC, bilateral anterior
insula, and putamen nucleus, and the deactivation of nociceptive
and sensory areas, including the thalamus and PAG. In contrast,
the placebo effect is associated with greater activation in the
bilateral dorsolateral PFC, PAG, thalamus, cerebellum, posterior
cingulate cortex, and superior frontal gyrus. SHAM mindfulness
activates brain areas that partially overlap with those activated
and deactivated by mindfulness, producing greater activation in
the thalamus, periaqueductal gray, bilateral dorsolateral prefrontal
cortex, and cerebellum and a minor activation in the posterior
cingulate cortex and right globus pallidus.
We also conducted a specific analysis of the control groups in
the studies, considering acute (Table 2) and chronic (Table 3) pain
separately, given the diversity of the analyzed outcomes. Two of the
19 studies were not included in the analysis because they did not
have a control group (Grazzi et al., 2021;Vencatachellum et al.,
2021) and were longitudinal evaluations of the interventions. As
previously mentioned, the main aims of the studies varied, such
as evaluating the opioid-mediated mechanisms of MBIs and/or the
MBIs themselves. Therefore, the control groups were specifically
designed, including saline infusion (e.g., Zeidan et al., 2016;Esch
et al., 2017;May et al., 2018;Namjoo et al., 2019;Wells et al., 2020;
Case et al., 2021;Khatib et al., 2024) or a specific placebo (Davoudi
et al., 2021).
Interestingly, the analysis of the control groups when the
interventions were MBIs frequently included interventions such as
passive controls, book listening, or educational programs (Zautra
et al., 2008;Zeidan et al., 2016;Esch et al., 2017;Case et al., 2021).
Controls more closely related to MBIs were also designed to equate
the non-specific features of the MBI (general Sham mindfulness),
stress management, or slow breathing techniques (Zeidan et al.,
2015;Seminowicz et al., 2020;Wells et al., 2020;Davies et al.,
2021,2022,2023;Khatib et al., 2024). A recent study included an
experimental group specific to the MBI, in which all conditions
matched the structural features of the MBI (e.g., attention to the
intervention and instructions designed to give the meditator the
sense that they were practicing a guided meditation) but lacked
the instructions to provide attentional stability and meta-awareness
(Davies et al., 2023).
The studies varied widely in terms of outcomes, covering
sensory (intensity and threshold) and cognitive-emotional (e.g.,
catastrophizing, anxiety, and depression) aspects. Among the 11
studies that specifically controlled for the MBI (and not the
pharmacologic intervention), MBIs had a similar effect to the
control intervention in at least one of the analyzed parameters.
These parameters included sensory aspects (Sharon et al., 2016;
Davies et al., 2021,2022,2023; pain intensity), emotional
components (pain unpleasantness; Davies et al., 2023), medical
consumption (Davies et al., 2023), and multifactorial parameters
(quality of life; Schmidt et al., 2011).
MBIs had a higher effect than the sham intervention in sensory
parameters (Zautra et al., 2008;Zeidan et al., 2015;Westenberg
et al., 2018;Seminowicz et al., 2020;Wells et al., 2020;Case
et al., 2021;Khatib et al., 2024; pain intensity) and several
cognitive/emotional aspects of pain (Zautra et al., 2008;Zeidan
et al., 2015;Westenberg et al., 2018;Davies et al., 2021). In none
of the analyzed studies did sham interventions have a higher effect
than MBIs.
To assess the quality of the studies included in this review, the
Cochrane Risk of Bias Tool for Randomized Controlled Trials was
used (Higgins et al., 2011), as well as the Newcastle-Ottawa Scale for
non-randomized studies (Tables 4,5). Most of the studies reviewed
have a moderate risk of bias, and therefore, the sample of articles
analyzed may be considered of good quality.
Discussion
To the best of our knowledge, this is the first systematic review
evaluating the possible effects of expectations and the placebo effect
on the outcomes of MBIs for pain management. Systematic reviews
support the efficacy of MBIs in pain management, suggesting
that these cognitive-behavioral therapies could be useful (Hilton
et al., 2017;Mcclintock et al., 2019;Pardos-Gascon et al., 2021).
However, these studies highlight the need for further research
due to the variability in the effects observed. This need is also
supported by the present systematic review since all analyzed
studies showed an effect of MBIs on pain management. Notably,
the studies often evaluated the effects of MBIs on both the
sensory and emotional dimensions of pain by measuring pain
intensity and pain unpleasantness, which is commendable given
the multidimensional nature of pain (Price, 2000;Raja et al.,
2020).
Further research is needed to understand the mechanisms of
MBIs in pain, considering the established effects of expectations
and placebo on pain and their neurobiological mechanisms
(Zunhammer et al., 2021;Benedetti et al., 2022). In this study,
we attempted to systematically evaluate whether participant
expectations of MBIs for pain were evaluated and whether the
potential for MBI-derived placebo effects was considered. Previous
systematic reviews and meta-analyses have suggested that the
mechanisms of action should be studied (Hilton et al., 2017;
Mcclintock et al., 2019;Pardos-Gascon et al., 2021). Given the
knowledge of placebo-induced analgesia, we hypothesized that
MBI-induced placebo effects could have an effect.
Despite the growing body of research on MBIs, the “next
generation of mindfulness-based intervention research”
(Rosenkranz et al., 2019) emphasizes the need for better
experimental designs to investigate the underlying mechanisms
of MBIs’ beneficial effects. In general, studies on MBIs, not only
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 2 Comparison of the eects of MBIs and sham (control) interventions in the acute pain studies, focusing on the main pain outcomes.
References Main mechanisms Type of sham
intervention
Pain outcomes
Intensity/
threshold
Tolerance Unpleasantness Catastrophizing
Case et al.
(2021)
Opioid-mediated
modulation of
expectations
- Active (Book
Listening) or
Passive control
- Saline infusion
MBI>Controls N/A N/A N/A
Davies et al.
(2021)
Placebo effects of MBIs Specific Sham
mindfulness
MBI=Control MBI=Control MBI>Control N/A
Davies et al.
(2022)
Role of expectations in
placebo effects of MBIs
Specific Sham
mindfulness
MBI=Control MBI=Control MBI=Control N/A
Esch et al.
(2017)
Opioid modulation - Passive control
- Saline infusion
N/A MBI=Control N/A N/A
May et al.
(2018)
Opioid modulation Saline infusion MBI>Control N/A MBI>Control N/A
Namjoo et al.
(2019)
Opioid modulation Saline infusion MBI>Control N/A N/A N/A
Sharon et al.
(2016)
Opioid modulation Saline infusion MBI=Control N/A MBI=Control N/A
Wells et al.
(2020)
Opioid modulation - Slow-paced
Breathing or Sham
Mindfulness
Meditation
- Saline infusion
MBI>Control N/A MBI=Control N/A
Zeidan et al.
(2015)
MBI vs. placebo
analgesia
- Placebo
conditioning
- General Sham
Mindfulness (GSM)
- Active control
(Book listening)
MBI>active
controls
(GSM)>Book
listening
N/A MBI>active controls
(GSM)>Book listening
N/A
Zeidan et al.
(2016)
Opioid modulation - Active (book
listening)
- Saline infusion
MBI>Control N/A MBI>Control N/A
MBI>Control means that the effect of MBI was significantly higher than the sham intervention.
for pain, should prioritize longitudinal evaluations and active
controls, as well as account for the instructors’ experience and the
participants’ expectations (Caspi and Burleson, 2007;Davidson
and Kaszniak, 2015;Van Dam et al., 2018). Additional research
using matched sham interventions is necessary in this field.
In a recent review of MBIs’ effects on fibromyalgia, we identified
several study limitations (Leca and Tavares, 2022), confirming that
experimental design concerns also apply to pain studies. Further
studies with adequate experimental designs are needed to better
evaluate the effects of MBIs, particularly regarding the instructors’
experience. In the present study, we found similar constraints
in the 19 analyzed studies, particularly regarding the instructors’
experience. A total of eight of the 15 analyzed studies did not report
the experience of the instructors. It was shown that the experience
of the instructors and their time of practice may influence the
outcomes of some MBIs (Davidson and Kaszniak, 2015;Van Dam
et al., 2018).
Attempts to contact authors for missing information were
unsuccessful. Two studies (Zeidan et al., 2015;Sharon et al., 2016)
did not have instructors, as their aims differed from the others,
reducing the number of relevant studies to 15 instead of 17 studies.
Other studies only mentioned that the instructors were
psychologists with expertise in mindfulness practices (Wells et al.,
2020;Davoudi et al., 2021), which is also vague information.
Some studies referred to both the extent of the instructors’
experience and the type of practice (Schmidt et al., 2011;Namjoo
et al., 2019). One additional constraint in the analyzed studies is
the lack of reporting and/or evaluation of participants’ previous
experience with mindfulness or meditation in six of the analyzed
studies (Zautra et al., 2008;Schmidt et al., 2011;Namjoo et al.,
2019;Case et al., 2021;Davoudi et al., 2021;Vencatachellum
et al., 2021). This is a challenging issue since participants’ prior
experience with mindfulness or meditation may prompt them to
recognize if they are receiving a sham intervention. Consequently,
these participants may not experience the same placebo effect as
those who believe they are receiving active treatment. This bias
could be mitigated by selecting participants who are completely
naive to mindfulness. Addressing these issues in future research
would be an important step in better understanding the factors that
influence MBIs’ effects on pain. Among the 19 analyzed studies, 10
used acute stimuli, while the remaining studies evaluated various
chronic pain conditions such as recurrent headaches/migraines,
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 3 Comparison of the eects of MBIs and sham (control) interventions in the chronic pain studies, focusing on the main pain outcomes.
References Main aim Type of sham
(control)
intervention
Main chronic pain outcomes
Severity/
intensity/
frequency
Pain-related
disability
Quality of life
(health related/
neuropathic-
specific)
Medication
consumption
Emotional distress
(unpleasantness/
catastrophizing/
anxiety/ depression/
coping)
Davies et al. (2023) Effects of Specific- and
General- sham
interventions
- General Sham
mindfulness (GSM)
- Specific Sham
mindfulness (SSM)
MBI=Controls (both
GSM and SSM)
GSM=SSM
N/A N/A MBI=Controls (both
GSM and SSM)
GSM=SSM
MBI=Controls (both GSM
and SSM)
GSM=SSM
Davoudi et al. (2021) Vitamin D effects Pharmacologic placebo MBI>Control MBI>Control MBI>Control N/A N/A
Khatib et al. (2024) Opioid effects in MBI and
Sham-MBI
- Sham-matched
mindfulness
- Saline infusion
MBI>sham mindfulness N/A N/A N/A N/A
Schmidt et al. (2011) MBSR in fibromyalgia General Sham
Mindfulness (GSM)
N/A N/A MBI=GSMaN/A N/A
Seminowicz et al. (2020) MBSR in headache Stress management MBI>Control N/A N/A N/A N/A
Westenberg et al. (2018) Mindfulness-based video
exercise
Attention placebo
control
MBI>Control N/A N/A N/A MBI>Control
Zautra et al. (2008) Mindfulness in arthritis Attention placebo
control (education)
M>ControlbN/A N/A N/A MBI>Controlb
MBI>Control means that the effect of MBI was significantly higher than the sham intervention.
aGeneral Active Sham (Active Control) had statistically significant effects in secondary outcomes in longitudinal analysis and comparison with passive control.
bDependent on history of recurrent depression.
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 4 Analysis of risk of bias for randomized controlled trials (Cochrane Risk of Bias Tool).
References Random and
sequential
sample selection
Blinded allocation
(the researcher does
not know the
treatment of the
next patient)
Single blinded or
double blinded
sample/patients
and/or investigators
Blinded
evaluation of the
results
Justification for
the cases of
withdrawal of
the study
Report of all
results (do not
select only
positive results)
Risk of bias
Case et al. (2021) Yes Yes Yes - Yes - Moderate
Davies et al. (2021) Yes Yes Yes - Yes Yes Moderate
Davies et al. (2022) Yes Yes Yes - Yes Yes Moderate
Davies et al. (2023) Yes Yes Yes - Yes Yes Moderate
Davoudi et al. (2021) Yes - Yes - No Yes High
Esch et al. (2017) Yes Yes Yes - No Yes Moderate
Khatib et al. (2024) Yes Yes Yes - No Yes Moderate
May et al. (2018) Yes Yes Yes - Yes Yes Moderate
Namjoo et al. (2019) Yes No Yes - Yes Yes Moderate
Schmidt et al. (2011) Yes Yes Yes No Yes Yes Moderate
Seminowicz et al. (2020) Yes Yes Yes Yes Yes Yes Low
Sharon et al. (2016) Yes Yes Yes - Yes - Moderate
Wells et al. (2020) Yes Yes Yes - Yes Yes Moderate
Westenberg et al. (2018) Yes No Yes - Yes Yes Moderate
Zautra et al. (2008) Yes Yes Yes - No Yes Moderate
Zeidan et al. (2015) Yes No No - Yes - High
Zeidan et al. (2016) Yes Yes Yes - Yes - Moderate
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Lopes et al. 10.3389/fnint.2024.1432270
TABLE 5 Analysis of risk of bias for non-randomized studies (Newcastle-Ottawa Scale).
References Selection Comparison Result/exposition Risk of bias
Adequate
definition
of cases
Representativeness
of cases
Selection of
controls
Definition
of controls
According to
the
methodology
Verification
of the
exposition
Same methods
for cases/controls
No
response
rate
Grazzi et al. (2021)∗ ∗ ∗ -∗ ∗ -∗Moderate
Vencatachellum
et al. (2021)
∗ ∗ ∗ ∗ ∗ ∗ ∗ - Low
diabetic neuropathy, and musculoskeletal/articular pain. However,
acute and chronic pain may differ in terms of the mechanisms
of mindfulness. Due to neuroplastic changes in the nervous
system from acute to chronic pain and the specificities of chronic
pain types, caution is needed when translating MBIs for pain
management in both acute and chronic pain.
There are still very few articles focusing on the role of
expectations in MBIs’ pain relief. There is a considerable gap
in the field of pain research, given that the role of expectations
in MBIs for other conditions has been demonstrated. The label
“mindfulness” in a study has been shown to drive expectancy
(Ghanbari Noshari et al., 2023), potentially leading to the
placebo effect. Since pain has a cognitive dimension and lacks
objective biomarkers, MBIs primarily rely on self-reported
experiences. Therefore, understanding patients’ expectations
and the information they received about the intervention
is crucial. However, our analysis revealed that most studies
did not clearly specify the type of information provided
to participants.
The information in the three studies that analyzed the effects
of MBIs on pain responses was clear. Two of these studies
concluded that the placebo effect plays a role in pain responses
during MBIs, with expectancy being the strongest predictor of
decreases in pain unpleasantness and intensity and increases
in pain tolerance (Davies et al., 2021,2022). In one study,
investigators created a cover story, informing the participants
that they would be allocated to one of two groups (mindfulness
or no treatment), while they were allocated to one of three
groups (mindfulness, sham mindfulness, or placebo; Davies et al.,
2021).
In another study, participants were informed that the aim
of the study was to test a newly developed MBI that integrated
highly effective elements of existing MBIs for pain and was
expected to greatly reduce pain. A similar cover story was
used, but participants were allocated to one of three groups
(mindfulness, sham mindfulness, or no treatment), while they
were, in fact, allocated to one of five groups (MM+: told they
were receiving mindfulness and actually received mindfulness;
MM-: told they were receiving sham but actually received
mindfulness; SHAM+: told they were receiving mindfulness but
actually received sham; SHAM-: told they were receiving sham
and actually received sham; and no treatment control). This design
demonstrated the effects of patients’ expectation on MBI results
for pain and the occurrence of a placebo effect (Davies et al.,
2022).
For a placebo effect to be accurately measured and controlled
for, the sham intervention must fulfill two roles. First, it must match
in credibility (i.e., from a participant’s or patient’s perspective, it
must be indistinguishable from actual mindfulness), as evidenced
by equivalent scores on credibility or manipulation checks.
Second, the sham intervention must elicit expectations of benefit
equal to those receiving mindfulness, as evidenced by equivalent
expectancy ratings post-exposure or by pre-exposure and post-
exposure changes in expectancy ratings across both groups. In this
regard, defining sham-mindfulness interventions or even sham-
mindfulness interventions with specific MBI features is crucial
(Davies et al., 2023) and may provide new insights into the specific
mechanisms of MBIs.
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Lopes et al. 10.3389/fnint.2024.1432270
Two studies focused on the effect of expectation on MBIs’ pain
relief. One of them hypothesized that mindfulness could reduce
cue-induced hypoalgesia and hyperalgesia and found evidence
to support the role of mindfulness in reducing cue-induced
hyperalgesia (Vencatachellum et al., 2021). The other study was a
secondary analysis of a previous study (Zeidan et al., 2016) and
demonstrated that the expectations of the participants about MBI-
induced pain relief predicted pain reductions, with the correlation
being higher during opioid antagonism (naloxone). Collectively,
the results of studies that properly control MBIs for factors such
as expectations show that these expectations should be considered.
The studies by the Davies group (Davies et al., 2022,2023) provide a
solid ground for collecting and numerically measuring participant
expectations to manipulate them and evaluate the placebo effect.
It should be noted that only a few studies have properly
measured and manipulated pain expectancies. Therefore, the
intentions of the participants in MBIs and their expectations
regarding pain improvement should be evaluated using appropriate
questionnaires before and after the interventions.
One study investigated the neurobiological mechanisms
underlying MBIs’ pain relief and whether they were similar to
those mediating the placebo effect (Zeidan et al., 2015). This
study concluded that MBIs produce greater pain relief than a
placebo intervention while engaging different brain mechanisms.
The differences in the magnitude of the effects and the underlying
brain structures indicate that the MBIs’ effects on pain relief are
not entirely mediated by placebo, although placebo plays a role.
However, the limited number of studies, along with some of the
abovementioned pitfalls in the experimental design, prevents solid
conclusions to be drawn about the influence of expectations on
“MBIs-induced” pain relief. Further studies are necessary to allow
additional systematic reviews and meta-analyses on this fascinating
issue in neuroscience, psychology, and medicine.
Overall, this systematic review indicates that certain aspects
of MBIs for pain management need to be considered before this
type of cognitive-behavioral intervention is widely adopted for
pain management. For example, it is important to determine the
expectations of the participants in the interventions, as these may
be manipulated to maximize placebo effects and better establish the
mechanisms behind the beneficial effects of MBIs. The importance
of including adequate sham controls should be highlighted in the
experimental design of MBIs for pain management. Regarding the
neurobiological mechanisms underlying the effects of MBIs on pain
management, such as opioid involvement, future neuroimaging
studies may be important. Due to the neuroplastic changes induced
by chronic pain and its impact on human suffering, it is crucial to
continue studying chronic pain rather than focusing predominantly
on acute pain. Evaluating the long-term impact of MBIs and
assessing the durability of treatment effects is also essential,
particularly for chronic pain conditions.
Limitations of the present study
This study presents some limitations. The small number of
studies that actually evaluated the effects of expectations was
much smaller than the 19 analyzed studies, which impairs the
ability to conduct a meta-analysis. Nevertheless, the large majority
of the studies were of good quality, as demonstrated by the
risk of bias assessment. Another limitation was the inability to
consistently retrieve data regarding the population, such as age and
gender, which considerably affect pain responses and responses to
psychological interventions such as MBIs.
It is important for researchers in MBIs for pain to openly
discuss the limitations and constraints of the current available
interventions to evaluate the mechanisms of the placebo effect in
MBIs for pain. Replicating studies that show that the placebo effect
plays a role in MBIs for pain (e.g., Zeidan et al., 2016;Davies
et al., 2022) would be important. There is a clear need for better
development, validation, and reporting of the sham interventions
used in MBIs. Longitudinal studies of novice and expert meditators
are necessary to evaluate how specific (mindfulness) and non-
specific (placebo) effects change over time with more training
and expertise.
Currently, there is a significant scope in MBIs for pain to
develop useful and specific placebo interventions, as the concept
of a “universal placebo” does not exist in MBIs. The present
systematic review also highlights the need to continue analyzing the
neurobiological basis of MBI to gain a better understanding of the
pain modulatory mechanisms, other than opioids, that may support
controlled therapeutic interventions of MBIs in pain management.
Data availability statement
The original contributions presented in the study are included
in the article/supplementary material, further inquiries can be
directed to the corresponding author.
Author contributions
AL: Conceptualization, Investigation, Validation, Visualization,
Writing – original draft, Writing – review & editing, Data curation,
Formal analysis, Methodology, Software. RS: Supervision,
Validation, Writing – review & editing. IT: Conceptualization,
Investigation, Validation, Visualization, Writing – original
draft, Writing – review & editing, Funding acquisition,
Resources, Supervision.
Funding
The author(s) declare financial support was received for the
research, authorship, and/or publication of this article. This study
was performed within the aims of Cátedra de Medicina da Dor
(Fundação Grunenthal, Portugal).
Conflict of interest
The authors declare that the research was conducted in the
absence of any commercial or financial relationships that could be
construed as a potential conflict of interest.
The author(s) declared that they were an editorial board
member of Frontiers, at the time of submission. This had no impact
on the peer review process and the final decision.
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Lopes et al. 10.3389/fnint.2024.1432270
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