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Efficacy, Treatment Characteristics, and Biopsychological Mechanisms of Music-Listening Interventions in Reducing Pain (MINTREP): Study Protocol of a Three-Armed Pilot Randomized Controlled Trial

  • Medizinische Hochschule Brandenburg (Theodor Fontane)

Abstract and Figures

Background: Pain can severely compromise a person's overall health and well-being. Music-listening interventions have been shown to alleviate perceived pain and to modulate the body's stress-sensitive systems. Despite the growing evidence of pain- and stress-reducing effects of music-listening interventions from experimental and clinical research, current findings on music-induced analgesia are inconclusive regarding the role of specific treatment characteristics and the biopsychological mechanisms underlying these effects. Objective: The overall aim of this pilot randomized controlled trial is to test and compare the differential effects of frequency-modulated and unmodulated music (both researcher-selected) on experimentally induced perception of acute pain and to test the efficacy of the interventions in reducing biological and subjective stress levels. Moreover, these two interventions will be compared to a third condition, in which participants listen to self-selected unmodulated music. Methods and Analysis: A total of 90 healthy participants will be randomly allocated to one of the three music-listening intervention groups. Each intervention encompasses 10 sessions of music listening in our laboratory. Frequency-modulation will involve stepwise filtering of frequencies in the audible range of 50–4,000 Hz. Acute pain will be induced via the cold pressor test. Primary (i.e., pain tolerance, perceived pain intensity) and secondary (i.e., heart rate variability, electrodermal activity, hair cortisol, subjective stress) outcomes will be measured at baseline, post, and follow-up. In addition, intermittent measurements as well as a follow-up assessment and a range of tertiary measures (e.g., music-induced emotions) are included. Discussion: This is the first study to systematically test and compare the effects of music frequencies along with the control over music selection, both of which qualify as central treatment characteristics of music-listening interventions. Results will be highly informative for the design of subsequent large-scale clinical trials and provide valuable conclusions for the implementation of music-listening interventions for the reduction of perceived pain. Clinical Trial Registration: Clinical Trials Database of the U.S. National Library of Medicine: Identifier NCT02991014.
Content may be subject to copyright.
published: 04 November 2020
doi: 10.3389/fpsyt.2020.518316
Frontiers in Psychiatry | 1November 2020 | Volume 11 | Article 518316
Edited by:
Anja C. Huizink,
Vrije Universiteit
Amsterdam, Netherlands
Reviewed by:
Satu M. Baylan,
University of Glasgow,
United Kingdom
Nóra Kerekes,
University West, Sweden
Urs M. Nater
These authors share first authorship
Specialty section:
This article was submitted to
Psychosomatic Medicine,
a section of the journal
Frontiers in Psychiatry
Received: 07 December 2019
Accepted: 22 September 2020
Published: 04 November 2020
Feneberg AC, Kappert MB,
Maidhof RM, Doering BK, Olbrich D
and Nater UM (2020) Efficacy,
Treatment Characteristics, and
Biopsychological Mechanisms of
Music-Listening Interventions in
Reducing Pain (MINTREP): Study
Protocol of a Three-Armed Pilot
Randomized Controlled Trial.
Front. Psychiatry 11:518316.
doi: 10.3389/fpsyt.2020.518316
Efficacy, Treatment Characteristics,
and Biopsychological Mechanisms of
Music-Listening Interventions in
Reducing Pain (MINTREP): Study
Protocol of a Three-Armed Pilot
Randomized Controlled Trial
Anja C. Feneberg 1†, Mattes B. Kappert 2† , Rosa M. Maidhof 1, Bettina K. Doering 3,
Dieter Olbrich 4and Urs M. Nater 1
1Clinical Psychology of Adulthood, Department of Clinical and Health Psychology, Faculty of Psychology, University of
Vienna, Vienna, Austria, 2Clinical Biopsychology, Department of Psychology, University of Marburg, Marburg, Germany,
3Division of Clinical and Biological Psychology, Department of Psychology, Catholic University Eichstätt-Ingolstadt, Eichstätt,
Germany, 4Center for Psychosomatic Rehabilitation, Klinik Lipperland, Bad Salzuflen, Germany
Background: Pain can severely compromise a person’s overall health and well-being.
Music-listening interventions have been shown to alleviate perceived pain and to
modulate the body’s stress-sensitive systems. Despite the growing evidence of pain- and
stress-reducing effects of music-listening interventions from experimental and clinical
research, current findings on music-induced analgesia are inconclusive regarding the role
of specific treatment characteristics and the biopsychological mechanisms underlying
these effects.
Objective: The overall aim of this pilot randomized controlled trial is to test and
compare the differential effects of frequency-modulated and unmodulated music (both
researcher-selected) on experimentally induced perception of acute pain and to test the
efficacy of the interventions in reducing biological and subjective stress levels. Moreover,
these two interventions will be compared to a third condition, in which participants listen
to self-selected unmodulated music.
Methods and Analysis: A total of 90 healthy participants will be randomly allocated to
one of the three music-listening intervention groups. Each intervention encompasses 10
sessions of music listening in our laboratory. Frequency-modulation will involve stepwise
filtering of frequencies in the audible range of 50–4,000 Hz. Acute pain will be induced
via the cold pressor test. Primary (i.e., pain tolerance, perceived pain intensity) and
secondary (i.e., heart rate variability, electrodermal activity, hair cortisol, subjective stress)
outcomes will be measured at baseline, post, and follow-up. In addition, intermittent
measurements as well as a follow-up assessment and a range of tertiary measures (e.g.,
music-induced emotions) are included.
Discussion: This is the first study to systematically test and compare the effects of
music frequencies along with the control over music selection, both of which qualify as
Feneberg et al. MINTREP: Study Protocol
central treatment characteristics of music-listening interventions. Results will be highly
informative for the design of subsequent large-scale clinical trials and provide valuable
conclusions for the implementation of music-listening interventions for the reduction of
perceived pain.
Clinical Trial Registration: Clinical Trials Database of the U.S. National Library of
Medicine: Identifier NCT02991014.
Keywords: autonomic nervous system, cold pressor test, music, music-induced analgesia, music intervention,
pain management, stress reduction
The experience of pain is a multifaceted and highly individual
phenomenon that involves sensory, affective, cognitive, social,
and biological components. Perceived pain can cause serious
disruptions in daily functioning and often compromises an
individual’s well-being and quality of life (1,2). While acute pain
is defined as a “sensory and emotional experience associated
with actual or potential tissue damage, or described in terms
of such damage” that is mostly unpleasant, though temporary
(3), chronic pain typically lasts several months or even years,
occurs with or without an underlying somatic cause, and affects a
large proportion of our society (4). For instance, pain conditions
including low back pain and migraine are amongst the leading
causes of disability and disease burden worldwide (4). In addition
to the individual suffering, the treatment of chronic pain is
associated with tremendously high direct and indirect costs
for society as a whole (5). For these reasons, chronic pain is
considered a global health challenge that needs to be treated by
affordable, effective, and well-accepted interventions (68).
Over the last decades, music as an adjuvant treatment for the
management of both acute and chronic pain has received growing
interest in clinical practice and scientific research [e.g., (9,
10)]. “Music-induced analgesia” offers several advantages, since
music is cost-effective, non-invasive, easy to (self-)administer
and does not have the drawback of severe side effects as
compared to most pharmacological treatments (11,12). A vast
body of evidence supports the pain-reducing effects of music in
diverse conditions, including surgical and chronic pain. While
surgical (i.e., postoperative) pain can be considered (mostly)
transient and functional to a certain degree (e.g., by causing
the individual to protect affected body parts), chronic pain is
not (or no longer) related to actual tissue damage, exceeds the
healing period and is therefore considered dysfunctional (13).
In a recent meta-analysis by Garza-Villareal et al. (14) including
14 randomized controlled trials and a total of 1,178 chronic
pain patients, music interventions (mostly listening to recorded
music) have been shown to reduce self-rated pain and comorbid
psychological symptoms with moderate to large effect sizes. Two
further meta-analyses of music-based interventions for cancer
patients also found effects on pain ratings in the moderate
to high range and additional positive effects on symptoms
of anxiety, depression, and autonomic functioning (15,16).
Moreover, various meta-analyses summarizing the empirical
evidence in the context of pre-, intra-, and post-operative periods
of surgery have documented beneficial effects of music on
ratings of pain and anxiety, as well as a reduction in anesthetic
medication intake during postoperative recovery (12,17,18). In
sum, the overall findings support the beneficial role of music-
based interventions for the reduction of pain in diverse settings
and patient populations. Nevertheless, it has been consistently
emphasized that methodological shortcomings and a large study
heterogeneity leave many questions unanswered [e.g., (11,12,
14)]. Therefore, despite a growing body of promising empirical
evidence, the literature on music-induced analgesia is still
inconclusive with regard to the optimal treatment characteristics
as well as the biopsychological mechanisms underlying the effects
of music listening on pain perception [see also (10)].
In addition to clinical studies with patient populations,
laboratory-based studies with healthy participants have
elucidated several important moderating and mediating
factors with respect to the effects of music listening on acute
pain perception (outlined below). Although the evidence from
these studies is certainly restricted in terms of generalizability to
chronic pain patients, such approaches allow standardizing the
magnitude of pain stimulation as well as keeping confounding
variables to a minimum (19), which is of great advantage when
investigating new treatment characteristics and mechanisms
of action. For these reasons, we will conduct a pilot study that
includes an experimental induction of acute pain in healthy
participants in order to determine the differential efficacy of
three music-listening interventions in reducing perceived pain
and to examine the biopsychological mechanisms underlying the
(potential) intervention effects.
Although various theories have been proposed with respect
to the psychological and biological mechanisms underlying
music-induced analgesia, the mediating processes are still not
yet very well-understood (9,10). The processing of pain is
modulated via descending pathways, neurotransmitter systems,
and neuronal/synaptic activity changes involving cortical and
subcortical brain regions, the brainstem, and the spinal cord
[see (20) for review]. Psychological processes, especially changes
in attention and emotional state, are suggested to influence the
processing of pain (21,22). In this context, many researchers
emphasize the distracting abilities of music and posit that
music binds cognitive capacities, diverts the listener’s attention,
and consequently inhibits pain sensations [e.g., (2325)]. In
addition, emotional engagement with music might explain
its pain-reducing effects. Particularly pleasurable music has
been shown to induce positive emotions (e.g., joy, pleasure)
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Feneberg et al. MINTREP: Study Protocol
in the listener and to modulate mood states (e.g., enhance
feelings of relaxation, decrease feelings of anxiety) (2628),
which are assumed to be associated with a downregulation of
pain experiences (2931). In addition, research in the fields of
neuroscience and psychoneuroendocrinology has revealed that
music affects a multitude of cortical und subcortical areas in
the brain, many of which are also involved in the processing
of pain, indicating that music-induced analgesia involves the
descending pain modulation pathway (9,32). For example,
previous experimental studies applying imaging techniques and
pharmacological manipulations (3335) have substantiated the
idea that pleasurable music affects dopaminergic and endogenous
opioid pathways that are associated with the brain’s reward
system. The release of dopamine and endogenous opioids in
response to pleasurable music could therefore qualify as a
possible biological pathway that leads to pain relief [see also (36)].
Furthermore, a biopsychological mediation model has been
advocated that proposes that the autonomic nervous system
(ANS) and subjective stress mediate the effects of music on pain
perception (37,38). In line with this idea, four recent systematic
reviews and meta-analyses have underlined the effectiveness
of music in decreasing biological and subjective markers of
stress (3942). The ANS is responsible for rapidly adapting the
individual to internal and external threats via a coordinated
interplay of its sympathetic and parasympathetic branch (43).
Consequently, the ANS is involved in the body’s processing
of and response to pain, which is reflected by changes in
biomarkers of the ANS such as heart rate, blood pressure, and
respiration rate (4446). Particularly heart rate variability and
skin conductance are of special interest, since these indicators
allow a relatively fine-grained interpretation of sympathetic and
parasympathetic activity (4749). Interestingly, the ANS is also
highly sensitive to musical stimulation (50,51). A prominent
model explaining the effects of music on ANS suggests that
music modulates activity in the limbic and paralimbic regions
including the hippocampus and the amygdala, which are also
involved in the regulation of ANS activity and the processing
of pain (9,52). To the best of our knowledge, only few studies
have investigated the effects of music on autonomic functioning
in the context of pain [e.g., (5356)]. In addition, we are not
aware of any experimental or clinical study that has explicitly
aimed at testing changes in ANS activity as a potential mediator
between music listening and pain perception. One exception
to this is a previous ambulatory assessment study from our
own lab, in which women diagnosed with fibromyalgia (i.e., a
condition characterized by chronic widespread pain) reported on
experiences of pain, stress, and their natural (i.e., experimentally
not manipulated) music listening behavior multiple times per
day over a duration of 14 days (38). The findings indicated
that control over pain was significantly enhanced by music
listening, but no effects on biological or subjective levels of stress
were found [in contrast to similar studies in healthy subjects,
e.g., (57)]. Therefore, the authors abstained from conducting a
mediation analysis. It is noteworthy that observational studies
conducted in patients’ everyday life are of high value with
regard to ecological validity (58); however, many parameters
in daily life research cannot be controlled for, particularly in
patient populations, and might have masked effects of music on
ANS activity. This, again, underlines the necessity for controlled
laboratory-based experimental studies with acute pain induction
in healthy participants in order to unravel mechanisms of action
underlying the effects of music listening on pain perception.
Next, we argue that structural elements of music and choice
over musical selection are two pivotal treatment characteristics in
music-listening interventions that lack a systematic investigation
in previous studies (10,59). In a recent meta-analysis by Martin-
Saavedra et al. (60), the common neglect of reporting musical
characteristics (e.g., tempo, instrumentation, presence of lyrics)
in previous randomized controlled trials investigating music
for pain management was criticized, since no clear conclusions
can be drawn based on the current literature. In this regard,
in their analyses of three experimental pain studies using
participants’ self-selected music, Knox et al. (61) found that
timbral and tonal aspects were significantly correlated with
measures of experimentally induced pain perception, indicating
that structural elements of music might differentially moderate
the effects of music on pain reduction.
In contrast to the relative lack of conclusive findings in the
field of pain management, musical characteristics such as sound
intensity, tempo, timbre, and arousal level have been shown to
affect ANS activity in a plethora of studies (6268). However, only
recently, audio frequencies, which constitute another inherent
feature of music, have been brought into focus of scientific
investigations (6972). From a technical perspective, the term
frequency describes the number of oscillations per time unit, i.e.,
for audio frequency, it is the number of vibrations per second
that determines the pitch of a sound and is measured in Hertz
(Hz). Music can be defined as a combination of a fundamental
frequency and multiple partial overtones, which are suggested to
be translated from the cochlea into neural activity in a first step,
followed by a pre-processing in the auditory brainstem, and are
then analyzed in the auditory cortex and other brain regions (52).
Nowadays, diverse commercial and free-to-listen compositions
with frequency-modulated music are available that are claimed
to exert a positive influence on the cognitive, emotional, social,
and physiological domains of their consumers. Typically, these
diverse programmes are based on different ideas about which
frequencies might be particularly beneficial or detrimental to the
human body and brain, with each programme thus justifying its
specific approach of frequency modulation (e.g., amplification or
filtering of certain frequencies) (73). Besides anecdotal evidence
on the potential benefits of these methods, scientific research
within this field is just in its infancy. For example, in the study
by Nakajima et al. (71), 12 healthy women underwent a stress-
inducing procedure three times in a row and listened to one
of three versions of the Horn Concerto in E-flat major, K.417
by Mozart, afterwards. The respective conditions comprised
the music piece modulated in the high-frequency spectrum
(equal of above 3.5 kHz), in the low-frequency spectrum (below
0.5 Hz), or not modulated at all. Heart rate variability (HRV) was
measured as dependent variable indicating autonomic recovery
during music listening. Results indicated that particularly the
modulation of high-frequency components was more effective
in supporting autonomic recovery compared to the other
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Feneberg et al. MINTREP: Study Protocol
conditions. In another study, Akimoto et al. (69) tested so-called
“solfeggio frequency music.” In their study, nine participants
listened to 5 min of “regular” relaxing piano music, i.e., tuned
to the international standard reference tone of 440 Hz, on 1 day,
and to the same piece tuned to a reference tone of 444 Hz (which
results in the inclusion of 528 Hz), on a different day. Biomarkers
of the ANS were assessed during and after exposure to music.
Results indicated subtle differences in HRV and significant
reductions in negative mood states in the 444 Hz (528 Hz), but
not in the 440 Hz music condition. Thus, findings from both
studies support the notion that specific frequency components
in music might be capable of differentially modulating the
activity of the ANS and psychological outcomes. Certainly, it is
necessary to interpret the data with caution and to recognize their
limited generalizability, particularly since both studies focused on
short-term effects of frequency-modulated music within a single
session and a small number of participants.
In addition to these experimental studies, recent investigations
applied a music intervention labeled “Audiovisuelle
Wahrnehmungsförderung” (AVWF R
)1, that involves a repeated
exposure to frequency-modulated music, in a clinical setting
(74,75). The authors found beneficial effects of this frequency-
modulated music intervention on HRV (74) and on the
cortisol-awakening response (i.e., indicator of the endocrine
stress system) in psychosomatic inpatients (75). These findings,
though preliminary, could indicate that the AVWF method
might have a beneficial impact on biological indicators of
stress in patients suffering from chronic conditions (74,75).
However, patients were not randomly assigned to treatment and
control groups in the study. Thus, it remains unclear whether
improvements in the variables of interest were actually caused
by the frequency modulation in the music, since the mere act
of music listening or other confounding aspects (e.g., selection
and performance bias) cannot be ruled out based on the current
findings (74,75). Consequently, in line with the evidence
reviewed above, it would be a critical endeavor to test if the
beneficial impact of music on pain perception can actually be
enhanced by a modulation of certain frequencies in music. Only a
randomized controlled trial that compares frequency-modulated
music with the same music in an unmodulated version and in
which both participants and examiners are blinded with regard
to frequency modulation allows drawing firm conclusions.
Furthermore, previous research is limited with regard to
systematic comparisons of the effects of control over choice
of music selection, i.e., researcher- vs. participants’ self-selected
music. Self-selected music might increase feelings of emotional
and cognitive involvement during music listening (31,55,76).
Self-selected music in contrast to pre-selected music is assumed
to better capture the listener’s personal preferences and is
therefore thought to be associated with a higher liking of
and familiarity with the music, as well as an increased sense
of control, all of which have been related to pain-reducing
effects (29,31,77). However, in some settings (e.g., hospital,
rehabilitation), it might be more practical to make use of
predetermined music selections. Therefore, some researchers
1A corresponding English translation is “Audiovisual Perception Enhancement”.
have opted for pre-selected (i.e., researcher-selected) music pieces
in the context of pain management such as slow, classical music,
since this is believed to be perceived as relaxing and pleasant
by most individuals [e.g., (78)]. Others offered participants to
choose pieces from a variety of musical genres in order to
permit some degree of personal preference [e.g., (79,80), see
also (81)]. Overall, self-selected music has been shown to be
superior to music chosen by researchers/clinical staff for pain
alleviation in patients with chronic pain conditions (14) and to
be superior to other distracting and emotionally engaging stimuli
in experimental studies with healthy participants (24).
A final shortcoming in previous research concerns the fact that
the existent body of studies is inconclusive with respect to the
stability of these effects (14). In previous laboratory-based studies,
experimental pain induction and music listening are typically
administered concurrently and in one session only [e.g., (31,
55,82)]. Although this is a valuable approach for investigating
the short-term impact of music on pain perception when
processed in parallel, these results are of limited validity with
regard to longer-lasting benefits of music for pain management.
Knowledge on the required length and amount of an intervention
is necessary in order to optimally balance spending of resources
(e.g., temporal, financial) and desired health outcomes. In the
context of music interventions for pain management, however,
previous studies are characterized by a remarkable variation in
length and frequency of music-listening sessions and whether
pain-reducing effects of music-based interventions last over
several weeks or even months have been examined only rarely.
For example, Finlay (83) found short-term, but no long-term
or cumulative effects of music listening on perceived pain
intensity and unpleasantness in chronic pain patients, whereas
other research groups found a steady increase in music-induced
analgesia over 2 (78) and 4 (84) weeks, respectively. However,
none of these studies included a follow-up assessment to test
whether the beneficial effects of music on pain perception lasted
even after cessation of the intervention period. In order to close
this research gap, we chose a long duration and high number
of music-listening sessions in addition to the inclusion of a (1
month) follow-up assessment in order to be able to investigate the
potential intermediate stability of the effects of music listening on
measures of pain perception.
This study addresses a number of open research questions
with regard to the overall efficacy, role of specific treatment
characteristics and biopsychological mechanisms of music-
listening interventions in reducing perceived pain.
First, we will investigate the pain-reducing effects of
frequency-modulated vs. unmodulated music, which are both
researcher-selected, within a randomized controlled, laboratory-
based, double-blind trial. Additionally, we include a third study
arm, in which participants will listen to their self-selected
(unmodulated) music. Since all study procedures (e.g., duration
and number of sessions and measurements) will be conducted in
parallel to the researcher-selected music-listening interventions,
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Feneberg et al. MINTREP: Study Protocol
we will be able to directly compare the differential effects of
all three music-listening interventions on measures of pain
perception. Furthermore, besides measures of pain perception,
we will investigate the effects of these three music-listening
conditions on biomarkers of the ANS and other stress-related
biological and subjective markers. In addition, we will test
whether changes in these markers of stress mediate the effects
of the music-listening interventions on perceived pain. We
will apply a laboratory-based, experimental paradigm for the
induction of acute pain (i.e., cold pressor test) at baseline,
post, and follow-up, as well as intermittently during the
intervention period.
Considering the complexity in design, assessments, and
procedure and the relative lack of conclusive previous findings,
we consider the current study a preliminary, though extensive,
pilot trial. The results of this pilot randomized controlled
trial (pilot-RCT) will be highly informative for the design and
evaluation of subsequent large-scale trials.
This pilot-RCT targets the following main hypotheses:
1. Listening to researcher-selected frequency-modulated music
and self-selected unmodulated music will result in stronger
increases in pain tolerance and stronger decreases in perceived
pain intensity from baseline to post-intervention compared to
listening to researcher-selected unmodulated music.
2. Stronger decreases in biological and subjective markers of
stress from baseline to post-intervention are expected in
the researcher-selected frequency-modulated music and self-
selected unmodulated music-listening conditions than in the
researcher-selected unmodulated music-listening condition.
Since there is no previous literature indicating a superiority
of researcher-selected frequency-modulated or self-selected
unmodulated music, we will test these comparisons in a two-
sided manner.
3. Changes in pain tolerance and perceived pain intensity will
be mediated by changes in biomarkers of the ANS and
subjective stress.
In addition to these main hypotheses, we will examine whether
reductions in measures of pain perception and markers of stress
persist until the follow-up assessment (4 weeks after the post-
assessment) aiming at investigating the potential intermediate
stability of the effects.
Moreover, we plan to conduct additional exploratory analyses
in order to unravel further health benefits as well as mediating
and moderating factors in association with the music-listening
interventions. For example, previous music research indicates
that music interventions might improve sleep quality (85), reduce
fatigue (86,87), and enhance mood (88). Moreover, empirical
evidence underlines the role of music-induced emotions and
memories (26,89), perceived musical valence and arousal (38,
57) as well as liking of and familiarity with the music (31,
90,91) among other music-related aspects for the effects of
music listening on perceived pain. Moreover, person-specific
characteristics such as cognitive style of music listening (92,93)
and music-related mood regulation strategies (94) have been
suggested to influence measures of pain perception and markers
of stress (82,95). Consequently, the current study aims at
investigating following additional questions: are the expected
pain- and stress-reducing effects stable after cessation of the
interventions? Do the interventions benefit further health-related
parameters, such as sleep and fatigue? What roles do music-
induced perceptions (i.e., emotions, memories, chills), perceived
music attributes (valence, arousal), changes in mood states,
as well as liking of and familiarity with the music play in
relation to measures of pain perception and markers of stress?
Do the habitual cognitive style of music listening and music-
related mood regulation habits moderate the effects of the
music-listening interventions on measures of pain perception
and markers of stress? In order to investigate these additional
questions, we will assess a comprehensive set of tertiary variables.
Study Design
The study is a laboratory-based, (double-)blind, randomized
controlled trial with three parallel arms: frequency-modulated
researcher-selected music, unmodulated researcher-selected
music and unmodulated self-selected music. Double blinding
with respect to frequency modulation will be achieved in the
researcher-selected music conditions, and participant blinding
will be ensured regarding frequency modulation within the
self-selected music condition. Figure 1 displays the study
flow chart.
Overall, 90 participants (30 participants per intervention
condition) will attend a baseline assessment, followed by 10
sessions of music listening conducted within 3 consecutive weeks.
Finally, post and follow-up assessments will be conducted. We
do not anticipate protocol modifications. Nevertheless, if any
trial modifications should be considered necessary, all changes
in design, measures, or eligibility criteria will be recorded in the
online protocol registration entry and will be included in the final
manuscript for journal submission.
Following the study preparation phase (April–November
2016), recruitment and testing started in December 2016 in
Marburg, Germany. Due to the move of our lab from Marburg,
Germany, to Vienna, Austria, recruitment and testing needed to
be paused as of January 2018 for 9 months. Testing continued
in October 2018 and is presumed to be accomplished in
December 2022.
Study Setting and Procedure
All 13 appointments (baseline, 10 music-listening sessions,
post-intervention assessment, follow-up assessment) will be
held in our laboratory. Since previous research indicates
that chronobiological rhythms influence perceived pain and
stress parameters (96,97), the appointments will be scheduled
exclusively between 12 and 6 p.m. The 10 music-listening sessions
(intervention period) will be scheduled within 3 consecutive
weeks. Baseline and post-assessments will be held as closely in
time as possible to the first and last music-listening session,
respectively. Some degree of variability between participants will
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Feneberg et al. MINTREP: Study Protocol
FIGURE 1 | Study flow diagram.
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Feneberg et al. MINTREP: Study Protocol
BOX 1 | Instructions for study appointments
No intake of analgesic medication on days of study appointments
• No use of body lotion or other fatty agents in the chest area (before
the appointment) to minimize artifacts in ECG recordings on days of
study appointments
• No consumption of alcoholic and/or energizing beverages or food, no
smoking, no excessive exercise or relaxation techniques (i.e., meditation,
yoga) for at least 1 hour prior to study appointments
Wearing of comfortable clothing during appointments.
be accepted in order to better enable participants to fit the large
number of appointments into their daily schedules.
After a telephone-based screening and upon inclusion,
participants will be scheduled a baseline appointment and receive
an email with instructions that they are asked to comply
with in order to prevent any interference with behavioral and
physiological measures (see Box 1).
Participants allocated to the self-selected music condition will
also receive an email attachment instructing them to compile
120 min of their favorite music pieces. This self-selected music
compilation should be brought to the first baseline assessment
on a portable device and handed to the examiner. At the end of
the baseline appointment, the examiner and participant arrange
further appointments for the subsequent 10 sessions of music
listening within the next 3 consecutive weeks.
At the beginning of each appointment, participants will be
asked to indicate whether any of the behaviors mentioned in
Box 1 (drinking alcoholic or energizing beverages, smoking,
etc.) apply. Additionally, the examiner will document whether
participants state being in a currently stressful phase (i.e., exams),
had poor sleep quality or short sleep duration during the previous
night, or have any current illness. Affirmation of intake of
analgesic medication at baseline, music-listening sessions 1, 3, 6,
10, post-, or follow-up assessments will lead to rescheduling of
the respective session since acute pain will be induced at these
appointments. The detailed protocol and timeline for baseline,
post, and follow-up appointments is displayed in Figure 2A,
the protocol and timeline for music-listening sessions 1, 3,
6, and 10 is depicted in Figure 2B. The examiner will be
blind regarding frequency modulation and will be in charge
of instructing the participants during the course of the study.
An independent second scientific staff member, unblinded with
regard to intervention conditions, will be in charge of adjusting
the music delivery systems (described below) according to the
respective music-listening intervention. This person will not
interact with the participants face-to-face at any time.
Study Population
Eligibility criteria are age between 18 and 35 years, body mass
index between 18.5 and 30 kg/m², fluency in speaking and
reading German, and ability to attend our laboratory for 10
appointments within 3 consecutive weeks. Participants of both
genders will be included (15 women and 15 men per group).
The following exclusion criteria are specified to ensure an
accurate delivery of the music-listening interventions:
- Perfect pitch
- Music-related studies (i.e., university level education)
or profession
- Impairment of hearing capability (e.g., chronic/acute tinnitus,
hearing loss).
Additionally, since our primary and secondary outcome
measures are susceptible to a range of lifestyle factors and
health conditions (98,99), and in order to reduce any potential
risk related to participation in the study, the following further
exclusion criteria will be applied based on participant self-report:
- Cardiovascular disease
- Artery occlusive disease
- Hyper-/Hypotension
- Diabetes
- Extreme visual impairment
- Chronic pain condition
- Raynaud syndrome
- Irregular menstrual cycle
- Pregnancy or breastfeeding
- Inability to refrain from smoking for more than 2.5 h
- Regular and problematic alcohol consumption
- Regular intake of pain medication and/or psychotropic drugs
- Mental disorders: current major depression/anxiety disorder;
current eating disorder or eating disorder within the past 5
years, current substance abuse or substance abuse within the
past 2 years; current or previous psychosis, schizophrenia, or
bipolar disorder
- Premenstrual syndrome
- Inability to self-identify as a man or woman.
Recruitment, Screening, and Consent
Participant recruitment will be conducted by advertising on
public notice boards, internet classified ads, social media sites
and via announcements in university classes. The study will be
presented to the public as “Music for stress management: A
music-based intervention study,” and a study email address will
be given for contact purposes. Interested potential participants
will be asked to send an email including their telephone number
in order to establish a first contact.
A two-step screening approach will ensure that only healthy
participants are included. First, prospective participants will
complete a telephone-based screening interview to check for
inclusion and exclusion criteria with regard to medical conditions
and lifestyle factors. Thereafter, the detailed study information
and an online link to confirm or decline study participation
will be sent to the positively screened participants. In the case
of confirmation, participants will be emailed a subsequent link
leading to an online survey including a battery of questionnaires
with further in-depth inclusion and exclusion criteria. If
participants screen positive for depression, pre-menstrual
syndrome or any psychiatric disorders apply [either based on
self-report within the telephone screening or based on the
online questionnaires, e.g., Patient Health Questionnaire (100),
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Feneberg et al. MINTREP: Study Protocol
FIGURE 2 | Protocol and timeline for study appointments: (A) baseline, post, and follow-up, (B) music-listening sessions 1, 3, 6, and 10.
Beck Depression Inventory-II (101), Premenstrual Syndrome
Questionnaire (102)], they will be excluded from the study. If no
exclusion criteria apply, participants will be randomly allocated
to one of the three music-listening interventions, and the baseline
appointment will be scheduled. The informed consent obtained
online will be corroborated by a personal signature at baseline.
Participants will be compensated for completion of the study
with 80 e. In the case of pre-mature termination of the study,
participants will be compensated proportionally.
We will use a block randomization stratified by gender using the
blockrand package (103) and the statistical software R, version
3.4.2 (104). Block lengths will vary randomly between 3, 6,
and 9. The randomization procedure will be performed by an
independent researcher unrelated to the study. The resulting
90 computer-generated notes stating participant gender and
experimental condition will be placed into separately sealed
envelopes and stored in a locked cabinet. Upon inclusion of a
new participant, the project coordinator will draw an envelope
containing the note with the respective condition to which the
included participant will be assigned. This information will be
shared with the scientific co-worker who will be in charge of
setting the music-delivery systems (see below) during the course
of the intervention period, but not with the experimenter.
To ensure that all participants across all conditions have similar
beliefs in terms of treatment expectancy, participation in the
study (as stated in the study information) implies random
assignment to either frequency-modulated or unmodulated
music, irrespective of selection of music (researcher- vs. self-
selection). The modulation of frequencies in our intervention is
not or only barely audible as confirmed in a pilot study conducted
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Feneberg et al. MINTREP: Study Protocol
in our own lab. Therefore, participants will be unable to detect
whether the music they listen to is frequency-modulated (or not),
and we will check participants’ assumptions concerning their
assigned condition at the end of the study (as described below).
With regard to frequency modulation in the researcher-
selected conditions, the participants and the examiner (who will
be in charge of instructing and interacting with the participants
throughout the study sessions) will be fully blinded. Similar
to participants in the researcher-selected music conditions,
participants in the self-selected music condition will expect to
hear either frequency-modulated or unmodulated music. Due
to technical constraints, however, frequency modulation will not
be applied in this study arm and participants will be exclusively
listening to unmodulated music. In this case, the examiner
interacting with the participants will be aware of the fact that
no frequency modulation will be applied. Consequently, apart
from the examiner’s and participants’ awareness of researcher-
selected vs. self-selected music, the study features a double-blind
design (examiner and participant) with regard to the frequency
modulation within the researcher-selected music arms and a
single-blind design (participant only) with regard to the self-
selected music arm. The scientific co-worker who will be in
charge of the music-delivery systems and administering the
correct music intervention to the participating subjects will be
fully aware of the respective conditions. Moreover, the study
coordinators will also be unblinded since they will be in charge
of assigning participants to examiners and scientific co-workers.
Neither scientific co-workers nor study coordinators will interact
directly with the participants.
At the end of the post-assessment, participants will be asked to
indicate which condition they believe they were allocated to (i.e.,
frequency-modulated or unmodulated music) in order to check if
blinding has been successful. After termination of the study (i.e.,
after the completion of the follow-up assessment), participants
will be debriefed with regard to their intervention allocation.
They will be further debriefed with regard to the study goals
and the fact that no frequency modulation occurred in the self-
selected music-listening condition. In the case of premature study
termination, participants will be debriefed accordingly.
Music-Listening Interventions
Each of the three music-listening interventions consists of
10 sessions of music listening within 3 consecutive weeks.
There is no pre-defined minimum number of sessions per
week in order to ensure integration of the intervention into
participants’ schedules. We chose a highly concentrated number
of intervention sessions since we assume a dose-dependent
effect on measures of pain perception and markers of stress
(38,105). Each music-listening session will encompass 60 min of
music listening and 10–20 min for additional data assessments
before and after music listening. Participants will receive
the intervention individually. During music listening, each
participant will be in a reclined position on a lounge chair and
will listen to the allocated music via headphones.
Frequency-Modulated Researcher-Selected Music
Frequency modulation and music pieces used in this arm are
comparable to the procedures of applications of AVWF-based
music interventions in previous clinical studies (74,75). Six
different mixes of music pieces are chosen that cover a wide
range of genres such as classic, instrumental, pop, rock, and
world music (see Box 2 for details). Three of these mixes are
compositions of known artists of which two also contain vocals.
The remaining three of the music mixes are instrumental music
pieces that were directly composed, recorded, and provided by
the developer of the AVWF method. Four of the six mixes will be
presented repeatedly within the 10 music-listening sessions. Each
mix has a length of 60 min. According to the AVWF method,
the applied music is modulated within the audible frequency
range of 50–4,000 Hz via a software system. This involves filtering
the harmonic overtones of low frequencies of the music pieces
presented in music-listening sessions 1–7. In sessions 8–10,
modulation will be additionally applied to frequencies in the
high spectrum. The modulated music will be transferred onto
a music delivery system (described below) which is equipped
with hardware components and additional modulating features,
increasing the magnitude of modulation from session to session.
This treatment is based on the assumption that listening to music
modulated in the low- and high-frequency spectrum improves
stress regulation and benefits the ANS via indirect stimulation of
afferent and efferent nerves within the auditory passage (106).
For persons with average hearing ability, the frequency
modulation is typically not detectable according to the AVWF
developer. We conducted a pilot study with a convenience
sample of 10 healthy subjects (seven women, three men, all
psychology students) in order to test whether participants
would be able to guess correctly if they listened to frequency-
modulated or unmodulated music. We randomly assigned
participants to one of the two conditions (5 per group) and
chose a composition of classic instrumental music that was
self-composed by the AVWF developer for both conditions.
Moreover, for the frequency-modulated music condition, we
decided to apply a modulation stage that would be usually
played during the sixth session (i.e., advanced modulation of
frequencies compared to the first sessions). Participants listened
to the respective music for a duration of 20 min in sitting
position via headphones. Afterwards, they filled out a paper-
pencil questionnaire asking them (a) to indicate whether the
music they listened to was presumably frequency-modulated or
unmodulated and (b) to estimate how confident they feel in
their answer on a VAS ranging from 0 to 100%. One participant
did not provide answers, leaving data from nine participants for
evaluation. Three participants (33.3%) allocated to the frequency-
modulated music made the correct guess with an average
confidence level of 50.3%. It is notable that one of these three
participants had visual impairments and reported extremely
good hearing abilities. Moreover, three participants (33.3%)
who were allocated to unmodulated music, guessed wrongly
and reported having been listening to frequency-modulated
music with an average confidence level of 43.0%. Furthermore,
one participant (11.1%) reported correctly having listened to
unmodulated music with a confidence level of 15.0% and
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BOX 2 | Overview of the music used in each music-listening session in the
researcher-selected music conditions.
ML session Title of Album(s) Artist(s)
1 Well-balanced Oliver Shanti
2 AVWF–Classics I AVWF®
3 QE2; Earth Moving Mike Oldfield
4 Violine Volume I AVWF®
5 The Beatles; The Beatles Munich Symphonic Sound
Orchestra; Classic Dream
6 See session 1
7 See session 4
8 See session 5
9 See session 3
10 Guitar I AVWF®
Participants will listen to a mix of music pieces of the specified album and
artist for 60 min in each session. Frequency modulation increases with
session number in the frequency-modulated researcher-selected
music-listening (ML) condition.
two participants (22.2%) thought they listened to unmodulated
music although they had been allocated to the frequency-
modulated music, with an average confidence level of 42.5%. In
summary, considering the 50% chance of guessing correctly and
that those who did guess correctly were not overall confident
in their estimation, we concluded from these results that
there was no systematic identification of frequency-modulated
music, confirming the notion that frequency modulation is
typically undetectable.
Unmodulated Researcher-Selected Music
The same music pieces in identical sequence as in the frequency-
modulated researcher-selected music condition (see Box 2) will
be presented to participants. However, music pieces will not be
frequency-modulated and will be presented via a music delivery
system without modulating features.
Unmodulated Self-Selected Music
Participants will receive an email before their baseline
appointment instructing them to compile 120 min of
their favorite music, irrespective of genre or other musical
characteristics (e.g., tempo, instrumental, vocal). Participants
will be assured that their personal selection will not be judged
in any way and that they should select songs or musical
excerpts that they will be able to enjoy listening to for 60 min.
Participants will also be advised to bring their compilation
on a portable memory device in mp3 format at their baseline
appointment, when the examiner will transfer the music onto
the study server and onto the music-delivery system without
modulating features for the subsequent 10 music-listening
sessions. During the intervention period, the self-selected music
will be played in shuffle mode in order to ensure variation
across and within sessions. On every occasion, the current
playlist will be recorded by the scientific co-worker for our
internal records.
Materials and Equipment
Music-Delivery Systems
Music will be presented via two different non-commercially
available music-delivery systems [as described in (75)]. One of
these will modulate the music via specific hardware components
while the other will play music unaltered. Both systems consist
of a computer with touch display and an amplifier built into a
wooden case and equipped with Windows media player software.
All participants will listen to their respective music via over-ear
headphones (beyerdynamic, Heilbronn, Germany).
Pain Induction
The cold pressor test (CPT) is a safe, reliable, and frequently
applied method to induce cold pain in experimental settings
(107,108). The CPT apparatus consists of a plastic bucket filled
with crushed ice and water. A metal grid placed into the bucket
holds the ice at the bottom of the bucket, and an electrical
pump constantly circulates the water to maintain a constant
temperature within the bucket. The target temperature is 1C and
is controlled by a thermometer. Participants are asked to immerse
their dominant hand into the water up to their wrist without
moving their hand or making a fist. Participants are instructed
to keep their hand in the water for as long as they can stand it. In
this study, participants will be facing a wall, and the examiner will
turn away from the participant in order to eliminate confounding
due to social desirability. When extracting their hand from the
water, the participants will be asked to signal this verbally to the
examiner. After a maximum duration of 3 min, participants will
be asked to pull their hand out of the water in order to prevent
any potential tissue damage. Moreover, participants do not know
after which of the music-listening sessions they will be exposed to
the CPT in order to avoid anticipation effects.
Outcome Measures
Course of Assessments
Table 1 reports the assessment schedule for measures of pain
perception as well as for biological and subjective markers
of stress. See Figure 2A for the protocol and timeline for
baseline, post, and follow-up appointments and Figure 2B for
the protocol and timeline for music-listening sessions 1, 3, 6,
and 10. In accordance with our hypotheses regarding measures
of pain perception and markers of stress, primary and secondary
outcomes will be measured at baseline and post-intervention.
Furthermore, to investigate the intermediate stability of potential
benefits of the music-listening interventions, we have included a
follow-up assessment 4 weeks after the post-assessment.
The intervention period encompasses 10 sessions of music
listening, each for a duration of 60 min, within 3 consecutive
weeks. Music-listening sessions 1, 3, 6, and 10 will also include
assessments of perceived pain in response to cold pain (induced
via the CPT after music listening) and continuous measurements
of biomarkers of the ANS as well as measurements of momentary
subjective stress before and after music listening, as well as before
and after the CPT. Furthermore, we will assess a range of tertiary
variables during the course of the study (e.g., music-induced
emotions, mood). The detailed assessment schedule including all
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TABLE 1 | Assessment schedule for measures of pain perception and markers of stress.
Measures Online survey BL Intervention period Post FU
M1 M2 M3 M4 M5 M6 M7 M8 M9 M10
Pain perception Pain tolerance (seconds) x x x x x x x
Perceived pain intensitya(VAS) x x x x x x x
Subjective stress Momentary stressb(VAS) x x x x x x x x x x x x x
Chronic Stress (SSCS) x x x
Stress reactivity (PSRS) x x x
Biological stress
HRVcx x x x x x x
EDAcx x x x x x x
Hair cortisol x x
The intervention period comprises 10 sessions of music listening (for a duration of 60 min each) scheduled within 3 consecutive weeks. Perceived pain will be induced via the cold
pressor test (CPT) at baseline (BL), music-listening sessions (M) 1, 3, 6, and 10 (after music listening, respectively), at post, and at follow-up (FU). Music-listening sessions 2, 4, 5, 7, 8,
and 9 comprise music listening only and no subsequent pain induction.
aPerceived pain intensity will be assessed pre- and post-CPT.
bMomentary stress will be assessed pre- and post-music listening and pre- and post-CPT.
cHRV and EDA will be derived from resting state (=10 min) at baseline, post, and follow-up; in addition, HRV and EDA will be measured continuously throughout music-listening sessions
1, 3, 6, and 10.
EDA, electrodermal activity; HRV, heart rate variability; PSRS, Perceived Stress Reactivity Scale; SSCS, Screening Scale for Chronic Stress; VAS, visual analog scale.
measured variables (primary, secondary, tertiary) is reported in
the Supplementary Tables 1, 2.
Primary Outcomes
Pain tolerance and perceived pain intensity: Pain tolerance will
be operationalized via time in seconds elapsed from immersion
until extraction of the hand during the CPT. It will be recorded
by the examiner using a stopwatch. Perceived pain intensity will
be measured before and after the CPT via paper-and-pencil visual
analog scales (VAS). Participants will be provided with a piece of
paper containing the sentence “I am in pain” and a 10 cm line
ranging from 0 to 100. They will be instructed to mark the line
accordingly (0 =no pain, 100 =maximal pain). Additionally,
after the CPT, participants will be asked to report how painful
they perceived the CPT to be by responding to the sentence “The
test was painful” and again marking a VAS corresponding to their
experience (0 =not at all painful, 100 =maximally painful).
Measures of pain perception will be assessed at baseline, post, and
follow-up as well as after music listening in sessions 1, 3, 6 and 10
(see Table 1 and Figure 2).
Secondary Outcomes
Since stress is a multidimensional phenomenon, we consider
biological (autonomic, endocrine) as well as subjective
indicators that operationalize different aspects and time-varying
characteristics of stress as our secondary outcomes (109).
Autonomic and Endocrine Stress Markers
Heart Rate Variability We will record an electrocardiogram
(ECG) at a sampling rate of 256 Hz for the analysis of heart
rate variability as an indicator of ANS activity using Equivital
EQ02 Life Monitors and Equivital Life Shirts (Hidalgo Limited,
Cambridge, UK). Time domain (e.g., square root of the mean
squared differences between successive RR intervals, RMSSD;
percentage of successive RR intervals that differ by more than
50 ms, pNN50) as well as frequency-domain (e.g., high-frequency
band, HF; low- to high-frequency ratio, LF/HF) indices (110) will
be calculated. At baseline, post, and follow-up, ECG recordings
will take place at rest for 10 min while watching a video
featuring landscapes (111) with the sound turned off. At the same
appointments, ECG will be additionally recorded continuously
(i.e., including pain induction). In music-listening sessions 1, 3,
6, and 10, ECG will be recorded constantly throughout the whole
session (i.e., including music listening and pain induction).
Electrodermal Activity Electrodermal activity (EDA) will be
recorded at a sampling rate of 16 Hz using Equivital EQ02
Life Monitors and corresponding EQ-ACC-034 EDA sensors
(Hidalgo Limited, Cambridge, UK). EDA will be derived from
the intermediate phalanx of the middle and index finger of the
non-dominant hand using pre-gelled Biopac EL507 electrodes
with Ag/AgCl contacts (Biopac Systems Inc., Goleta, CA, USA).
Recording will take place analogously to ECG recordings.
Hair Cortisol Cortisol is the main effector hormone of the
hypothalamic-pituitary adrenal axis, an important stress-
sensitive system besides the ANS. The secretion of cortisol is
increased upon exposure to environmental stressful situations
and accumulates in hair, reflecting a measure of chronic stress
exposure (112). Hair samples for the subsequent analysis of hair
cortisol will be taken at baseline and follow-up assessment. Three
strands of hair will be taken scalp-near from the posterior vertex
region. The most scalp-near 1 cm of hair will be analyzed as this
represents cortisol secretion in approximately the last month
and thus gives insight into each individual’s cumulative stress
exposure over the month before sampling. In the context of this
study, we will thus be able to assess chronic biological stress in
the 4 weeks before baseline and in the 4 weeks before follow-up
(reflecting the timeframe between the post-measurement and
follow-up assessment).
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Subjective Stress Measures
Subjective Momentary Stress We will measure momentary
subjective stress via VAS (paper-and-pencil) before and after
music listening in all 10 music-listening sessions and before
and after conducting the CPT (i.e., at baseline, music-listening
sessions 1, 3, 6, 10, post, and follow-up). On each occasion,
participants will be asked to respond to the sentence “I am feeling
stressed” using a VAS ranging from 0 (not stressed at all) to 100
(maximally stressed).
Chronic Stress We will use the Screening Scale for Chronic Stress
(SSCS) comprising 12 items of the Trier Inventory of Chronic
Stress (TICS) (113) at baseline, post, and follow-up assessment to
measure subjective chronic stress. We have adjusted the reference
period in the instructions of the SSCS from 4 weeks to 1 week
so that baseline and post-assessment will not overlap. The TICS
encompasses 57 items on six subscales (work overload, worries,
social stress, lack of social recognition, work discontent, intrusive
memories) and will be used at baseline, too.
Stress Reactivity Stress reactivity will be measured by the German
version of the Perceived Stress Reactivity Scale (PSRS) (114),
administered at baseline, post, and follow-up assessment. The
PSRS consists of five subscales (Prolonged Reactivity, Reactivity
to Work Overload, Reactivity to Social Conflicts, Reactivity to
Failure, Reactivity to Social Evaluation) which can be combined
into one overall scale.
Tertiary Variables
Tertiary variables will be assessed throughout the study. These
may serve as outcome, control, moderator and/or mediator
variables in exploratory analyses related to the study. The
assessment schedule for tertiary variables is displayed in the
Supplementary Tables 1, 2.
In each music-listening session, momentary mood [short
scale of the Multidimensional Mood Questionnaire, MDMQ-
short (115)] will be assessed directly before and after music
listening. Additionally, based on previous literature investigating
the impact of music on measures of pain perception and
stress, we developed a questionnaire assessing music-related
perceptions concerning the respective music that was listened
to. The questionnaire will be provided after music listening
in each session. It includes questions on music-induced
emotions, perceived valence and arousal of the music,
music-induced memories, and is also thought to control for
mind-wandering or sleeping during the music-listening sessions
(see questionnaire 1 in online Supplementary Material).
Furthermore, musical engagement between sessions will be
assessed (see questionnaire 2 in online Supplementary Material)
as a potential control variable.
At baseline, post, and follow-up assessments, the following
additional variables will be assessed via questionnaires: emotion
regulation strategies [Emotion Regulation Questionnaire, ERQ
(116)], fatigue [Multidimensional Fatigue Inventory, MFI-20
(117)], sleep quality [Pittsburgh Sleep Quality Index, PSQI
(118)], and depressive symptoms [Beck Depression Inventory-
II, BDI-II (101)]. Moreover, at baseline only, cognitive style
of music listening (Music-Empathizing-Music-Systemizing
(ME-MS) Inventory), music preferences [revised version of
the Music Preference Questionnaire, MPQ (119)], personality
traits [openness to experience, conscientiousness, extraversion,
agreeableness, neuroticism, Big Five Inventory-10 (120)],
perceived social support [subscale of the Berlin Social Support
Scales, BSSS (121)], and menstrual cycle phase (self-report) will
be assessed.
For the purpose of monitoring the participants during
the intervention period, they will receive paper-and-pencil
questionnaires with open-ended questions at the end of music-
listening sessions 1, 3, 6, and 10. This will enable them to
report whether they felt any disturbances associated with the
music-listening session and whether they had any specific
thoughts during the CPT in order to control for cognitive pain-
coping strategies.
At the end of the post-assessment, participants will receive
a paper-and-pencil post-monitoring questionnaire, asking them
to indicate which condition (i.e., frequency-modulated or
unmodulated music) they believe they were assigned to and how
confident they are in this belief. Moreover, participants will be
asked whether they perceived increased self-awareness due to
study participation, whether any positive or negative changes in
well-being, mood, or general health occurred during the course of
the intervention, and to state how compatible study participation
was with their individual schedules. At the follow-up assessment,
final post-monitoring and control questions regarding musical
engagement, previous familiarity with and use of music-listening
interventions and study conformity will be assessed.
Sample Size Determination
Previous investigations employing a comparable design are
lacking and we consider the current study a pilot trial in order
to yield sufficient precision for a sample size calculation in a
subsequent full trial. Therefore, following the recommendations
mentioned in (122,123) and (124), we decided to test 30
participants in each group. A power analysis using GPower 3
(125) suggested that this sample size will be sufficient to achieve
a medium effect (f=0.25) in a repeated-measures analysis
of variance (α=0.05, power (1-β)=0.80) with condition
as the between-subject factor (frequency-modulated researcher-
selected vs. unmodulated researcher-selected vs. self-selected)
and time (baseline vs. post) as the within-subject factor. In
the case of dropouts, we will continue recruitment and repeat
the randomization procedure until at least a number of 30
participants is collected in each group. Thus, the final number
of participants in each group might slightly differ.
Statistical Analysis
Repeated-measures analyses of variance will be conducted to
test our main hypotheses 1 and 2. Mediation hypotheses will
be tested with continuous time modeling procedures. P-values
of 0.05 will be considered statistically significant. Analyses
for comparisons between the researcher-selected frequency-
modulated and self-selected unmodulated music conditions will
be conducted in a two-sided manner. Any further exploratory
analyses will be specified in future publications. We will perform
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both per-protocol and intention-to-treat analyses. Missing data
will be imputed in accordance with (126).
Ethical Considerations
The study has been approved by the Local Ethics Committee
of the Department of Psychology of the University of Marburg
(2016–27k) and the Local Ethics Committee of the University
of Vienna (00331). It is preregistered on
(Identifier: NCT02991014). The study has begun in Marburg
(recruitment and testing from December 2016 until December
2017) and will be continued in Vienna. Potential participants
will be informed about the procedure and general aims of
the study. Participants will be told that they will be randomly
assigned to a researcher-selected or self-selected music-listening
condition; they will be told that their respective music might be
frequency-modulated. In fact, only researcher-selected music will
be frequency-modulated. This deception is necessary to avoid any
confounding effects due to expectancy bias. Written informed
consent will be obtained from all participants. Participants can
withdraw from the study at any time. All participants will be
debriefed upon completion of or withdrawal from the study.
Conducting the CPT will be painful. Nevertheless, in order to
study effects of music-based interventions on pain, it is essential
to evoke pain. Participants can withdraw their hand at any
time. Maximum immersion time will be limited to 3 min to
ensure the safety of the procedure. To further rule out any risk,
persons suffering from conditions like cardiovascular diseases,
Raynaud syndrome or high or extremely low blood pressure will
be excluded from participation.
Results of this research study will be presented at national
and international conferences and published in a peer-reviewed
journal. In accordance with the recommendations of the German
Psychological Association (DGPs) (127), primary data of this
study will be made available in an electronic online repository.
Data Monitoring and Management
A data monitoring committee has not been established since
this study is considered to be of minimal risk. Questionnaires
that are administered electronically will be saved in a password-
protected online database. Paper-and-pencil questionnaires will
be stored in a locked cabinet. They will be entered into and saved
in electronic files on a regular basis. Access to study data will be
limited to research staff who require direct access.
After inclusion of a new participant (i.e., after online
confirmation of study participation and successful online
screening), the participant will be allocated a unique study code
(sequential number), which will be used for all further study
documentation to ensure confidentiality. All data analysis will
be performed via study code only. The master files that connect
the unique participant codes with sensitive person-related
information will be stored separately in a locked cabinet with
limited access.
Music-listening interventions are an effective adjuvant for the
management of pain and stress. There is still uncertainty
concerning the role of particular treatment characteristics for
the effects of music-listening interventions on measures of pain
perception and markers of stress. Some authors argue that certain
frequencies in music might be especially useful for alleviating
perceived pain and stress, and suggest that musical stimuli
should be modulated accordingly. Moreover, some researchers
emphasize the importance of high standardization in the design
of music-listening interventions and thus argue in favor of
music selection by researchers, while others advocate self-
selection of musical stimuli by participants to achieve beneficial
effects. Furthermore, very few studies have investigated both
measures of pain perception and markers of stress together,
making it difficult to unravel the potential role of stress in
pain perception.
This study aims to determine potential influences of
frequency modulation as well as of self- vs. researcher-
driven selection of music stimuli in terms of the efficacy in
reducing perceived pain and markers of stress. Moreover,
while there is comprehensive evidence of direct effects of
music-based interventions on pain perception, we seek
to investigate whether these effects might be mediated by
changes in biomarkers of the ANS and subjective stress and
whether this can result in long-term benefits. To address
these open questions, we designed a randomized controlled,
laboratory-based, double-blind pilot trial comparing frequency-
modulated researcher-selected music with unmodulated
researcher-selected music. In addition, we included a third
condition, in which participants will listen to their self-selected
unmodulated music.
Certain limitations of our study warrant consideration. Due
to technical constraints, we will not have the opportunity
to conduct frequency modulation on music, which is self-
selected by participants. Thus, our design does not allow us
to test a possible interaction between frequency modulation
(modulated or unmodulated) and selection (self-selected or
researcher-selected). In addition, the procedures for participants
randomized to the self-selected music condition are not entirely
comparable to the procedures for participants in the researcher-
selected music conditions: participants in the self-selected music
condition will spend time and effort in selecting their favorite
pieces of music whereas this does not apply to participants in
the researcher-selected music condition. In case of significant
differences between these two conditions, we cannot completely
rule out that the effects depend, in part, on the act of listening
to music that one has chosen in an effortful process or other
confounding aspects instead of the music per se. Examining
these mechanisms lies, however, beyond the scope of the current
study and has been discussed elsewhere with suggestions on
how to disentangle the confounding variables (e.g., increased
control over choice, familiarity) in studies investigating self-
and researcher-selected music (10). Furthermore, due to the
repeated exposure to the CPT, the possibility of desensitization
effects needs to be considered. There are not many studies that
Frontiers in Psychiatry | 13 November 2020 | Volume 11 | Article 518316
Feneberg et al. MINTREP: Study Protocol
investigated intervention effects on cold pressor pain including
a repeated exposure to the CPT. However, those that did,
found that there were no desensitization effects with respect to
pain tolerance (128). Furthermore, considering biomarkers of
the ANS, Minkley et al. (129) found no desensitization effects
on blood pressure during repeated exposure to the (socially
evaluated) CPT, however, desensitization of heart rate was
documented. Other studies suggest that ANS activity remains
unaffected by repeated exposure to the cold pressor test if the
recovery period is long enough (130), which applies to the present
study. Importantly, if desensitization effects should occur in the
present study, we would assume that these affect participants
across conditions due to the randomization and would thus
apply to all three conditions. Therefore, systematic differences in
pain perception between the conditions should stay unaffected.
Moreover, we are only able to investigate the effect of one
specific method of frequency modulation. However, we chose
to investigate this particular approach, since the AVWF method
has been applied in clinical research with patients suffering
from stress-associated disorders with first positive results (74,
75). Consequently, it seems a reasonable starting point to test
specifically the AVWF method and to investigate its potential
to reduce perceived pain and markers of stress in a pilot-
RCT. Another limitation concerns the lack of a non-musical
control condition (e.g., listening to an audio book or another
type of non-musical auditory stimulation). However, adding
such a group would be of limited use because this would
merely allow us to test whether music per se has an effect
compared to non-musical auditory stimuli. The effectiveness of
music per se in reducing pain (14,17) and stress (39,41) has
already been shown in various studies. Thus, given the costs
of including an additional control group, we did not deem
such a group necessary in order to answer our study questions
within the current pilot-RCT. Furthermore, considering the 4
weeks between the post- and follow-up assessments, it might
be argued that this is a rather short timeframe in order to
investigate the stability of potential benefits of the music-listening
interventions. However, in the context of our study, stability
needs to be considered in the context of the experimental nature
of the study, such that it might provide initial evidence on
how long potential effects could last in healthy participants.
If our results reveal preliminary evidence for effects enduring
for 4 weeks after termination of the interventions, this would
clearly underscore the importance of further examinations of
such effects in a subsequent study, which may include chronic
pain patients and a longer duration until follow-up assessment.
Finally, we will only recruit healthy young adults in a laboratory
setting using experimentally induced pain, which obviously
differs from real-life pain conditions in several ways, such as
the individual’s possibility to stop the pain-inducing procedure
at any time (19). Thus, the generalizability of findings will be
limited. Nevertheless, in order to investigate biopsychological
mechanisms, we consider it important to examine potential
effects in a well-controlled, highly standardized design first,
before conducting studies with clinical populations in more
naturalistic settings.
Apart from the above-mentioned limitations, there are
several strengths of our study. To the best of our knowledge,
this is the first study to test effects of frequency-modulated
music vs. researcher-selected music on experimentally induced
acute pain using a longitudinal, randomized controlled and
double-blind design. By including a third condition, i.e., self-
selected unmodulated music we will be able to compare the
differential effects of the three music-listening interventions and
to fill research gaps that have been documented in the literature
(9,10,14). Moreover, by including measures of biological
and subjective stress, the current study will address secondary
variables that have been proposed to mediate the effects of
music on pain perception (37,38). Unlike most previous studies,
we will not investigate effects on measures of pain perception
during concurrent music listening but will instead test whether
even after cessation of listening to music an effect on pain
perception can still be achieved. This will enable us to investigate
the potential stability of the pain-reducing effects of music
listening—at least within an intermediate time-frame, an aspect
that is currently highly under-researched (14). Moreover, we
will measure a great variety of tertiary variables such as sleep
quality, fatigue, mood, and music-related perceptions, allowing
us insights into the effects of music on many domains of health.
Consequently, this study is the first important step toward
a deeper understanding of the efficacy, the role of treatment
characteristics (i.e., frequency modulation, control over selection
of music) and biopsychological mechanisms underlying the
phenomenon of music-induced analgesia. The results from
the current pilot-RCT will provide important information
on the differential effects and effect-sizes on perceived
pain as well as the potential biopsychological mechanisms
underlying the effects of the three employed music-listening
interventions on perceived pain. These findings are pivotal
for the sound design of future large-scale randomized
controlled trials focusing on the effects of particular music-
listening interventions for the reduction of pain. In addition,
although preliminary, results from this study will be highly
informative for the implementation and improvements of
music-listening interventions offered to acute and chronic
pain patients.
The study has been reviewed and approved by the Local Ethics
Commitee, Department of Psychology, University of Marburg,
Marburg, Germany (2016–27k), and the Local Ethics Commitee,
University of Vienna, Vienna, Austria (00331). All participants
will provide their written informed consent to participate in
this study.
AF, MK, BD, DO, and UN designed the study. AF, MK, and RM
wrote the first draft of the manuscript. All authors reviewed and
edited the manuscript and approved its final version.
Frontiers in Psychiatry | 14 November 2020 | Volume 11 | Article 518316
Feneberg et al. MINTREP: Study Protocol
The authors acknowledge funding by the Research Platform The
Stress of Life (SOLE) - Processes and Mechanisms underlying
Everyday Life Stress.
The authors would like to thank Birga Bohn for her involvement
in designing parts of the study. They further thank José Carlos
Garcia Alanis and Dr. Kristina Klaus-Schiffer for support with
the randomization procedure. Moreover, the authors would
like to acknowledge that the music-delivery systems and music
mixes that will be used in the study are kindly provided by
Ulrich Conrady.
The Supplementary Material for this article can be found
online at:
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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.
Copyright © 2020 Feneberg, Kappert, Maidhof, Doering, Olbrich and Nater. This
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Frontiers in Psychiatry | 18 November 2020 | Volume 11 | Article 518316
... The use of a single VAS for the assessment of subjective acute stress has been validated in a clinical context [110] and is also widely used in other studies in related research fields (e.g. Feneberg et al., [111]; Thoma et al. [32]). ...
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The pain- and stress-reducing effects of music are well-known, but the effects of visual art, and the combination of these two, are much less investigated. We aim to (1) investigate the pain- and (2) stress-reducing effects of multimodal (music + visual art) aesthetic experience as we expect this to have stronger effects than a single modal aesthetic experience (music/ visual art), and in an exploratory manner, (3) investigate the underlying mechanisms of aesthetic experience, and the (4) individual differences. In a repeated-measures design (music, visual art, multimodal aesthetic experience, control) participants bring self-selected “movingly beautiful” visual artworks and pieces of music to the lab, where pain and stress are induced by the cold pressor test. Activity of the pain and stress responsive systems are measured by subjective reports, autonomic (electrocardiography, electrodermal activity, salivary alpha-amylase) and endocrine markers (salivary cortisol).
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Auditory stimulation training (AST) has been proposed as a potential treatment for children with specific language impairments (SLI). The current study was designed to test this assumption by using an AST with technically modulated musical material (ASTM) in a randomized control group design. A total of 101 preschool children (62 male, 39 females; mean age = 4.52 years, SD = 0.62) with deficits in speech comprehension and poor working memory capacity were randomly allocated into one of two treatment groups or a control group. Children in the ASTM group (n = 40) received three 30-min sessions per week over 12 weeks, whereas children in the comparison group received pedagogical activities during these intervals (n = 24). Children in the control group (n = 37) received no treatment. Working memory, phoneme discrimination and speech perception skills were tested prior to (baseline) and after treatment. Children in the ASTM group showed significantly greater working memory capacity, speech perception, and phoneme discrimination skills after treatment, whereas children in the other groups did not show such improvement. Taken together, these results suggest that ASTM can enhance auditory cognitive performance in children with SLI.
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Music has been associated with alterations in autonomic function. Tempo, the speed of music, is one of many musical parameters that may drive autonomic modulation. However, direct measures of sympathetic nervous system activity and control groups and/or control stimuli do not feature in prior work. This article therefore reports an investigation into the autonomic effects of increases and decreases in tempo. Fifty-eight healthy participants (age range: 22–80 years) were randomly allocated to either an experimental (n = 29, tune) or control (rhythm of the same tune) group. All participants underwent five conditions: baseline, stable tempo (tune/rhythm repeatedly played at 120 bpm), tempo increase (tune/rhythm played at 60 bpm, 90 bpm, 120 bpm, 150 bpm, 180 bpm), tempo decrease (tune/rhythm played at 180 bpm, 150 bpm, 120 bpm, 90 bpm, 60 bpm) and recovery. Heart rate, blood pressure, respiration, and muscle sympathetic nerve activity were continuously recorded. The 60 bpm in the tempo decrease stimulus was associated with increases in measures of parasympathetic activity. The 180 bpm in the tempo increase stimulus was also associated with shifts towards parasympathetic predominance. Responses to the stimuli were predicted by baseline %LF. It is concluded that the individual tempi impacted upon autonomic function, despite the entire stimulus having little effect. The 60 bpm in an increasingly slower stimulus was associated with greater vagal modulations of heart rate than faster tempi. For the first time, this study shows that response direction and magnitude to tempo manipulations were predicted by resting values, suggesting that music responders may be autonomically distinct from non-responders.
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Music interventions are used for stress reduction in a variety of settings because of the positive effects of music listening on both physiological arousal (e.g., heart rate, blood pressure, and hormonal levels) and psychological stress experiences (e.g., restlessness, anxiety, and nervousness). To summarize the growing body of empirical research, two multilevel meta-analyses of 104 RCT, containing 327 effect sizes and 9,617 participants, were performed to assess the strength of the effects of music interventions on both physiological and psychological stress-related outcomes, and to test the potential moderators of the intervention effects. Results showed that music interventions had an overall significant effect on stress reduction in both physiological (d = .380) and psychological (d = .545) outcomes. Further, moderator analyses showed that the type of outcome assessment moderated the effects of music interventions on stress-related outcomes. Larger effects were found on heart rate (d = .456), compared to blood pressure (d = .343) and hormone levels (d =.349). Implications for stress-reducing music interventions are discussed.
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The autonomic nervous system as operating system of the human organism permeats all organ systems with its pathways permeating that it is involved with virtually all diseases. Anatomically a central part, an afferent part and sympathetic and parasympathetic efferent system can be distinguished. Among the different functional subsystems of the autonomic nervous system, the cardiovascular autonomic nervous system is most frequently examined with easily recordable cardiovascular biosignals as heart rate and blood pressure. Although less widely established, sudomotor tests pose a useful supplement to cardiovascular autonomic assessment as impaired neurogenic sweating belongs to the earliest clinical signs of various autonomic neuropathies as well as neurodegenerative disorders and significantly reduces quality of life. Clinically at first, the autonomic nervous system is assessed with a detailed history of clinical autonomic function and a general clinical examination. As a lof of confounding factors can influence autonomic testing, subjects should be adequately prepared in a standardized way. Autonomic testing is usually performed in that way that the response of the autonomic nervous system to a well-defined challenge is recorded. As no single cardiovascular autonomic test is sufficiently reliable, it is recommended to use a combination of different approaches, an autonomic test battery including test to measure parasympathetic and sympathetic cardiovascular function (deep breathing test, Valsalva maneuver, tilt, or pressor test). More specialized tests include carotid sinus massage, assessment of baroreceptor reflex function, pharmacological tests or cardiac, and regional hemodynamic measurements. Techniques to measure functional integrity of sudomotor nerves include the quantitative sudomotor axon reflex sweat test, analysis of the sympathetic skin response as well as the thermoregulatory sweat test. In addition to these rather established techniques more recent developments have been introduced to reduce technical demands and interindividual variability such as the quantitative direct and indirect axon reflex testing or sudoscan. However, diagnostic accuracy of these tests remains to be determined. We reviewed the current literature on currently available autonomic cardiovascular and sudomotor tests with a focus on their physiological and technical mechanisms as well as their diagnostic value in the scientific and clinical setting.
This proceedings paper is the first in a series of three papers developing mathematical models for the complex relationship between pain and the sleep-wake cycle. Here, we briefly review what is known about the relationship between pain and the sleep-wake cycle in humans and laboratory rodents in an effort to identify constraints for the models. While it is well accepted that sleep behavior is regulated by a daily (circadian) timekeeping system and homeostatic sleep drive, the joint modulation of these two primary biological processes on pain sensitivity has not been considered. Under experimental conditions, pain sensitivity varies across the 24 h day, with highest sensitivity occurring during the evening in humans. Pain sensitivity is also modulated by sleep behavior, with pain sensitivity increasing in response to the build up of homeostatic sleep pressure following sleep deprivation or sleep disruption. To explore the interaction between these two biological processes using modeling, we first compare the magnitude of their effects across a variety of experimental pain studies in humans. To do this comparison, we normalize the results from experimental pain studies relative to the range of physiologicallymeaningful stimulation levels. Following this normalization, we find that the estimated impact of the daily rhythm and of sleep deprivation on experimental pain measurements is surprisingly consistent across different pain modalities. We also review evidence documenting the impact of circadian rhythms and sleep deprivation on the neural circuitry in the spinal cord underlying pain sensation. The characterization of sleep-dependent and circadian influences on pain sensitivity in this review paper is used to develop and constrain the mathematical models introduced in the two companion articles.
Background: Stress and anxiety are increasingly common among young people. The current research describes two studies comparing the effects of self-selected and researcher-selected music on induced negative affect (state anxiety and physiological arousal), and state mindfulness. Method: In Study 1, 70 undergraduates were randomly assigned to one of three conditions: researcher-selected music, self-selected music, or a silent control condition. In Study 2, with 75 undergraduates, effects of music were compared to an active control (listening to a radio show). Negative affect was induced using a speech preparation and arithmetic task, followed by music listening or control. Self-reported anxiety and blood pressure were measured at baseline, post-induction, and post-intervention. Study 2 included state mindfulness as a dependent measure. Results: Study 1 indicated that participants who listened to music (self-selected and researcher-selected) reported significantly greater anxiety reduction than participants in the silent control condition. Music did not reduce anxiety compared to an active control in Study 2. However, music listening significantly increased levels of state mindfulness, which predicted lower anxiety after self-selected music listening. Conclusions: Music may provide regulation in preparation for stressful events. Yet, the results of Study 2 indicate that other activities have similar benefits, and shows, for the first time, that music listening increases mindfulness following a stressor.
When studying the factors which influence stress reactivity in within-subject designs, test-retest reproducibility data is needed to estimate power and sample size. We report such data regarding a new experimental stress protocol, based on simultaneous application of the socially evaluated, bilateral feet Cold Pressor Test (CPT) and the Paced Auditory Serial Addition Task (PASAT). Cardiovascular, neuroendocrine, and subjective (affective) stress responses of 32 healthy males were measured twice, at an interval of one week. The novel protocol induced substantial stress reactivity in all parameters at both test and retest. Cardiovascular reactivity remained unchanged, but cortisol and subjective responses were lower at second stress exposure, with high test-retest stability of neuroendocrine (r>.7) and cardiovascular measures (r = .5 to r = .9). PASAT performance improved. Response attenuation suggests habituation-like and/or learning effects. Data provided by our study demonstrate feasibility and power of this stress protocol for investigating changes in stress reactivity in repeated, within-subject designs.
Background Cross-sectional and experimental knowledge highlight the contribution of various health-promoting behaviors, such as physical activity, regular sleep, and healthy nutrition to mental and physical health. Beyond these well-studied lifestyle behaviors, music listening and perceived respect in social interactions are just recently proposed everyday life experiences, which may act as health-promoting factors. Purpose This study tested the simultaneous contribution of several health-promoting behaviors and factors and examined listening to music and positive social interaction by means of perceived respect as new potentially preventive and health-promoting behaviors and factors using an ambulatory assessment design. Methods Seventy-seven young healthy adults (38 women, 23.9 ± 4.5 years) completed surveys on their psychological state (i.e., mood, stress, and fatigue) five times a day for four consecutive days. A saliva sample was collected with each data entry to explore the physiological stress markers salivary cortisol, alpha-amylase, and flow rate as further outcome variables. As predictors, perceived respect, self-reported physical activity, the sleep’s restfulness, daily coffee, alcohol, vegetable/fruit consumption, and music listening behavior were recorded. Results Overall, restful sleep, mean daily perceived respect, and listening to music were most clearly associated with more positive psychological states, that is, better mood and lower fatigue and perceived stress. Associations with daily alcohol, coffee, and vegetable/fruit consumption appeared rather minor. While perceived respect scores were associated with lower daily cortisol output, coffee consumption was positively related to daily cortisol and alpha-amylase. Self-reported physical activity was unrelated to either outcome measure. Conclusions These findings provide important insights regarding potential resources of health (i.e., music and respect), their covariation, and which psycho-physiological mechanisms may underlie the links between health factors and well-being. Findings also have implications for the development of interventions aiming to increase resilience and foster health. Here, strategies for improving sleep quality, the use of music, and approaches that emphasize mutual respect and appreciation appear useful additions.
Chronic pain is a common, complex, and distressing problem that has a profound impact on individuals and society. It frequently presents as a result of a disease or an injury; however, it is not merely an accompanying symptom, but rather a separate condition in its own right, with its own medical definition and taxonomy. Studying the distribution and determinants of chronic pain allows us to understand and manage the problem at the individual and population levels. Targeted and appropriate prevention and management strategies need to take into account the biological, psychological, socio-demographic, and lifestyle determinants and outcomes of pain. We present a narrative review of the current understanding of these factors.
Purpose: Pain, anxiety, and nervousness related to dental procedures can cause acute changes in the autonomic nervous system. Music is widely accepted as a relaxation method during dental treatment; however, its effects during dental treatment are unclear. The authors explored the effects of listening to music during extraction of the impacted mandibular third molar on the autonomic nervous system and the psychological state and hypothesized that listening to music would suppress sympathetic nervous activity and decrease anxiety. Materials and methods: In this prospective study, 40 patients scheduled for extraction of an impacted mandibular third molar were randomized into 2 groups: extraction without music (control group) and extraction while listening to music (music group). Heart rate variability was recorded during the experiment, and Modified Dental Anxiety Scale and State-Trait Anxiety Inventory (STAI) scores were recorded before and after the procedure. Descriptive and bivariate statistics were computed and the P value was set at .05. Results: An increased low-to-high frequency ratio was observed in the control group during incision and flap reflection, bone removal, and separation of the tooth crown; the ratio was significantly decreased in the music group during these time points (P < .05). Compared with the control group, the music group had a significantly greater decrease in postoperative STAI State Anxiety scores from preoperative levels (P < .05). Conclusions: This study suggested that listening to music while undergoing extraction of the impacted mandibular third molar suppresses activity of the sympathetic nerves during incision, flap reflection, bone removal, and separation of the tooth crown and relieves anxiety after treatment. Future studies will focus on the mechanisms involved and methods to prevent the onset of systemic incidents.