The Analgesic Effects of Music and Chronic Pain: A

Narrative Review

Sacha Moufarrej
Department of Neuroscience, University of Washington

Abstract

Chronic pain has become a significant public health concern, with prevalence rates in the US
ranging between 11 and 40%. With no cure for this family of disorders, treatment has turned
toward management of symptoms. Current research has promoted the development of a
biopsychosocial model for the mechanisms of chronic pain, and a richer understanding of
neuropathology may improve upon cognitive, behavioral, and other alternative therapies for
chronic pain. One such proposed alternative treatment is music therapy, based on the analgesic
effects of music that have been documented for millennia. This study aims to provide a narrative
synthesis of current research on the neural mechanisms of chronic pain, the circuitry that
underlies music-induced analgesia, and the application of these neuropsychological findings to
the development of effective music therapies.

Introduction

As a leading cause of disability and a major interconnectivity of neural populations

reason for physician visits, the prevalence of within the brain, through which a complex
chronic pain on a global scale has created a perception of the physical self is attained
distressing economic and public health [21]. While originally developed through the
issue. Patients with chronic pain often also study of phantom limb pain, this theory
experience comorbid conditions, such as extended the original pain research on gate
depression and anxiety, which contribute to control by emphasizing the dynamic nature
the disabling effects of these conditions [8]. of the brain, and showed the ways in which
Current traditional medical and these parallel and cyclical circuits could be
pharmaceutical treatments have resulted in hijacked [18]. Melzack’s work was critical
an epidemic of opioid abuse, medications to the understanding that this modulation,
which have been proven effective for acute whether due to injury or idiopathic causes,
pain treatment but largely ineffective and was not solely based on sensory inputs, and
harmful for chronic pain. Thus, researchers emphasized that the brain itself was the key
and clinicians have begun to look for to understanding pain as a sensory,
alternative therapies that aim to manage psychological, and cognitive human
symptoms, as opposed to cure chronic pain. experience.
In 1990, a revolutionary theory of This biopsychosocial model for the
pain perception emerged that highlighted the neuropathology of chronic pain has provided
role of the brain and central processing: the an effective theoretical foundation for
neuromatrix theory, developed by Ronald research into the mechanisms of music-
Melzack. This theory describes the induced analgesia. The healing powers of
music have been documented for millennia, the amygdala, a structure that contributes to
and music has been and continues to be a emotional processing [1]. In addition, when
prevalent therapy for a variety of ailments. comparing acute or transient and chronic
Now, through the development of functional pain centralized activation, fMRI results
neuroimaging technologies and show a greater increase of the activity in the
advancement of neurological research, the prefrontal cortex (PFC) in patients with
anatomical and physiological bases of the chronic pain, supporting the hypothesis that
previously anecdotal and subjectively modulation of pain processing pathways
experienced effects of music are being results in a greater cognitive and emotional
identified. This research has great experience of pain in the chronic state [1].
implications for the acceptance of music- These studies also indicate a decrease in
based therapies for chronic pain, an activity in the ACC and Th in chronic pain
inherently biopsychosocial experience. participants compared to healthy controls [9,
However, to our knowledge, there currently 24].
is limited synthesis of the research done on More recently, the nucleus
pain processing and on music-induced accumbens (NAc), a key region of the basal
analgesic mechanisms supported by clinical ganglia, has been studied for its role in
trials and neuroimaging results. Thus, the motivation, reward, and pain processing.
aims of this article are to provide a narrative The NAc receives glutamatergic inputs from
review of recent work on pain processing various cortical regions (including the PFC,
and music-induced analgesia (MIA), analyze ACC, amygdala, and hippocampus) and
the commonalities in their cortical circuitry, dopaminergic inputs from the midbrain’s
and determine the efficacy of current music ventral tegmental area, the latter of which
therapy trials. encodes reward value of various
environmental stimuli [27]. It has previously
Neurobiology of Pain: Central Nervous been implicated in its role in the
System Mechanisms of Chronic Pain development of addiction, and is a key
Processing modulatory region that affects the pain
experience in the presence of opiate input
Recent imaging studies have [4]. NAc medium spiny neurons with D2
provided greater insight into the central dopamine receptors have specifically been
mechanisms of pain processing and the ways implicated in the indirect inhibition of action
in which these mechanisms are altered in as a response to aversive stimuli, such as
chronic pain disorders. The brain regions pain: D2 receptors are responsible for a
implicated in pain processing are: 1) the pathway of inhibition within this
primary and secondary sensory cortex (S1 subpopulation of NAc neurons, and are
and S2), responsible for preliminary themselves inhibited by dopamine [4].
perception of sensory and nociceptive Recent functional neuroimaging
stimuli; 2) the insular cortex (IC), whose studies, both in humans and animal models,
complex role in higher-level functions is still have shown plasticity in the NAc that may
being studied, and which is thought to play a contribute to the experience of chronic pain.
role in the subjective experience of pain; 3) Increased synaptic transmission between the
the anterior cingulate cortex (ACC), which NAc and PFC in patients with chronic pain
contributes to attention and emotional implies the augmentation of emotional and
modulation; 4) the thalamus (Th), a key hub reward/punishment circuitry in chronic pain
for exchange of neural information, and 5) processing. D2 medium spiny neurons show
increased activation in chronic pain from injury, post-surgically, or from cancer
participants, due to a decrease in and neurological degeneration. However,
dopaminergic input, which is the source of many cases prove to be idiopathic, and
inhibition in this subset of NAc neurons [4]. genetic research indicates the presence of
Other studies have shown a change in potential biomarkers involved in the
galanin receptor 1 (GalR1) in neurons of the pathogenesis of chronic pain disorders [7].
NAc, which are critical for the activation of The prevalence of idiopathic chronic pain
AMPA and NMDA receptors for the continues to support a comprehensive
excitatory neurotransmitter glutamate. As biopsychosocial model.
mutations in GalR1 arise, a desensitization
of AMPA receptors is observed, leading to a
period of long-term depression, in which The Neural Mechanisms of Music-
synaptic activation is reduced. This Induced Analgesia
mechanism has been hypothesized to be
related to comorbid depressive symptoms in Neuroimaging research on the
patients with chronic pain [30]. neurological processing of music has used
the neuromatrix theory as the foundation for
studying music-induced analgesia (MIA),
and has focused on increasing our
understanding of the effects of musical
stimuli on the descending pain modulatory
system (DPMS) that constitutes the
aforementioned cortical structures [11]. The
numerous sources of modulation within this
pain matrix—including emotion, sensation,
expectation, attention, neurotransmitter
dysfunction, and genetics—have led
researchers to postulate the similarity in the
anatomical bases of musical and pain
processing [32].
Figure 1. Pain Processing Neuromatrix [4]. Through functional neuroimaging,
Salimpoor et al (2013) have shown that
Overall, it appears that the several regions within the brain are recruited
centralized mechanisms responsible for pain in response to stimulation using desirable
processing are modulated as pain becomes a new music. The circuits between the NAc
chronic condition. The neuromatrix theory, and the ventromedial PFC, amygdala,
supported by functional neuroimaging, hippocampus, ACC, and S1 and S2 were
emphasizes the inherent interconnectivity strongly activated as participants listened to
that alters the cognitive processing of pain, desirable music, the desirability of which is
as it incorporates sensory, emotional, and measured through participant surveys [28].
endogenous neuromodulatory input to As previously discussed, these connections,
provide a more holistic view of the ways in and the NAc especially, play a significant
which idiopathic chronic pain develops. role in reward value and emotional
It is important to note that chronic processing: as dopamine release increases in
pain disorders have a variety of underlying response to a rewarding stimulus, activation
causes. For some, chronic pain can develop of cortical structures, such as D2-expressing
medium spiny neurons in the NAc, one system with the vibrational frequency of
increases, in direct opposition to the another system” [16]. Research has shown
decrease in response found to play a role in that the oscillations and synchrony present
comorbid depressive symptoms in patients in the physical manifestation of music may
with chronic pain [23, 28]. These findings affect a person’s physiological rhythms,
are corroborated in rat models, where the establishing a resonance that modulates
use of “melodic music” stimuli increased heart rate, blood pressure, respiratory rate,
endogenous levels of dopamine and and cortical activity [5, 29]. Hauck et al’s
serotonin, resulting in greater activation of study of neural oscillations also provides a
the dopaminergic and serotonergic caudate look at this entrainment theory, using a more
putamen (CPu)—a structure within the active music therapy approach. The
striatum that is implicated in emotional researchers found that patient composition
processing, motivational drive, and perhaps of “healing” music, defined by its positive
most importantly within this context, emotional valence, yielded decreased
anticipation of reward or pleasure—and the gamma band activity in S1, indicating that
dopaminergic NAc [22]. this synchronization of high frequency
The theoretical basis of MIA excitation (40-100 Hz) plays a role in
mechanisms can be divided into three sensitization during early stages of pain
dimensions: distraction, entrainment, and processing [14]. These gamma waves have
emotional modulation. also been implicated in higher cortical
processing functions, and their reduction
Music and Distraction during music therapy may signify
modulation in emotional processing and
Pain has been recognized as an descending control of pain [14].
attention-demanding perceptual process;
thus, numerous cognitive behavioral Music and Emotional Modulation
therapies have been developed based on the
idea of providing a distraction from pain [6]. Finally, since patients with chronic
Studies of neural oscillations support pain disorders often experience comorbid
psychological observation of the efficacy of mental health disorders, such as highly
distraction mechanisms: the use of receptive prevalent depression and anxiety, these
music stimuli (or pleasurable music symptoms provide a clear target for clinical
listening) showed a decrease in the power research and alternative treatment. As
and amplitude of delta-band activity (0-4 previously mentioned, music processing is
Hz) in the cingulate cortex and anterior largely characterized by activation and
insula, indicative of distraction within modulation of various emotional processing
structures implicated in pain processing, pathways: greater dopaminergic excitation
specifically those that draw conscious of the NAc, for example, seems to improve
attention to pain [14, 19]. activation of neurons whose inhibition is
often associated with depression [23].
Music and Entrainment Similarly, an increase in levels of serotonin
in the CPu overrides the reduction of
Entrainment is defined as a process serotonergic activity that is often linked to
in which “two previously out-of-step depression [22]. By combining a distraction
oscillators lock into phase with one another, from the attentional bias for negative
replacing the vibrational rate or frequency of information, with stimulatory endogenous
excitatory neurotransmitter release in combatting both the physical and
emotional processing circuits, and psychological components of chronic pain
enhancement of the internal locus of control, [13]. As stated above, the body responds
music can provide a useful, non-invasive physiologically to music, whether through
therapy for decreasing depressive symptoms distraction, entrainment, or emotional
and facilitating the stimulation of positive modulation, and effects both homeostatic
mood states [10,12]. Previous clinical and cognitive processes.
psychological research has shown that the There is a growing body of clinical
emotional valence of music is key to the research that supports the use of music as a
efficacy of music-induced analgesia, in management therapy for patients with
which music with positive emotional chronic pain disorders. Assessment of pain,
valence significantly decreases the depression, and anxiety levels in music
experience of anxiety and stress within a therapy studies have consistently shown
painful environment [26]. decreases in these varying physiological and
neuropsychological symptoms, as music
Music Therapy for Chronic Pain therapy often fulfills at least one of the three
dimensions previously discussed [3,10,11,
The goals of chronic pain treatment 15, 20]. However, this literature has
differ, or should differ, greatly from those of emphasized that passive listening to music
acute pain treatments. Reducing pain may not be enough. Thus, researchers have
intensity is neither necessary nor sufficient begun differentiating between music
for effective chronic pain care. Rather, the medicine as a passive experience, and music
suffering that is often experienced in therapy as an active, individually developed
patients with chronic pain is more often management treatment [16].
produced because of the fundamental It is notable that self-selected music
implication of chronicity as “pain that has seems to cause a greater positive physical
no meaning or known end” [31]. In fact, the change than randomized music. This is
reliance on “pain intensity readings” and important when thinking about conducting
opioid prescriptions is a contributing factor music therapy [14, 16, 17, 20]. Creating a
to the opioid epidemic that has spread across strong rapport between the music therapist
the United States: the relentless focus on and patient is key to the development of
decreasing pain intensity promotes the individualized care. This is a limitation of
prescription of opioids for chronic pain much of the empirical research on music-
conditions. While advantageous for induced analgesia, in which researchers
treatment of acute pain, opioids have no often use randomized, unknown music,
proven benefits for chronic pain patients. disregarding the preferences of the
Long-term opioid use, at best, has no effect participants. This most likely leads to
on pain intensity, and at worst, dramatically inaccuracy in the results of the efficacy of
increases pain and leads to substance abuse, music therapy for chronic pain patients.
overdose, and death. While music cognition research often
Music therapy is a prime example of requires the analysis of music’s “objective”
an effective therapy that shifts from the structural features—such as pitch, timbre,
current medicalized approach to a more valence, and rhythm—this approach may be
holistic approach to pain treatment. Rather reductionist within the context of music
than focusing on augmenting a patient’s therapy [25]. A patient’s experience of
physical health, music is effective in music is informed by the structural aspects
of the music in conjunction with treatment of the whole biopsychosocial,
enculturated preferences, leading to a model enculturated being.
of overlapping emotional and cognitive
processes across various cultures [2]. Thus,
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