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Running head: EMPATHY FOR PAIN 2
EMPATHY FOR PAIN And its Neural Correlates
Bachelor Degree Project in Cognitive Neuroscience
Basic level 15 ECTS Spring term 2016
Emelie Löfstrand
Supervisor: Judith Annett Examiner: Paavo Pylkkänen
Running head: EMPATHY FOR PAIN 2
Abstract
The phenomenon of empathy has been fascinating laymen and scholars for centuries and has
recently been an important subject for cognitive neuroscientific study. Empathy refers to the
ability to understand and share others’ emotions and a characteristic of this ability is the
capacity to empathize with others in pain. This review intends to examine and read up on the
current state of the field of the neural and behavioral mechanisms associated with empathy for
pain. The neural underpinnings of the first-hand experience of pain have been shown to be
activated in a person observing the suffering individual, and this similarity in brain activity
has been referred to as shared networks. This phenomenon plays an important role in the
study of empathy. However, different factors have been shown to influence empathy for pain,
such as age, gender, affective link between observer and sufferer, as well as phylogenetic
similarity. This thesis discusses these differences, as well as atypical aspects affecting the
empathic ability such as synaesthesia for pain, psychopathy and Asperger’s disease. Further,
empathy for pain can be modulated by the individual observing someone in pain. For
example, caregivers often down-regulate their empathic response to patients in pain, possibly
in order to focus on their treatment and assistance. Also, paying attention to harmful stimuli
heightens the perception of pain; therefore, the painful experience can be less remarkable
when focusing on something else. The effect of empathy from others directed to oneself when
suffering is discussed, as well as the consistency and limitations of presented research.
Keywords: empathy, pain, shared networks, pain matrix, empathy for pain
EMPATHY FOR PAIN 3
Table of Contents
Introduction 5
Empathy 9
Neural Correlates of Empathy 9
Mirror neurons 9
The empathy circuit 11
Pain 13
Theories of Pain 13
Gate control theory of pain 15
Pain Pathways 17
Neural Correlates of Pain 18
Empathy for Pain 19
Neural Correlates of Empathy for Pain 19
Shared networks 21
Somatosensory system 22
Factors Influencing Empathy for Pain 23
Age 23
Gender 25
Empathy for non-human entities 26
EMPATHY FOR PAIN 4
Empathy among caregivers 27
Racial bias 28
Atypical Aspects of Empathy for Pain 30
Synaesthesia for pain 30
Psychopathy 31
Huntington’s disease 32
Asperger’s syndrome 33
Post-traumatic stress disorder 34
Regulation of Empathy for Pain 35
Empathy Affects Pain Perception 37
Conclusions 38
References 43
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Introduction
The term “empathy” derives from the Greek word “empatheia” (passion),
composed of “en” (in) and “pathos” (feeling). It was introduced into the English language
from the German word “einfûhlung” (feeling into), which was then referred to as resonance
with works of art, but later on came to describe the resonance between humans (Singer &
Klimecki, 2014). The phenomenon of empathy and its many facets have been fascinating
laymen and scholars for centuries (Lamm & Majdandžić, 2015). In the late 20th century,
researchers began to study this phenomenon on a scientific level. (Singer & Klimecki, 2014)
In order to explain empathy, we first need to clarify how it differs from other
related states which also have to do with the sharing of emotions. Empathy is commonly
referred to as the ability to understand or feel what another being is experiencing (e.g. Singer
& Klimecki, 2014; Fan & Han, 2008; Mu, Fan, Mao, & Han, 2008). According to some
researchers, the sharing of emotions is a conscious process in which the other individual is
considered the source of the state or the feeling (Betti & Aglioti (2016). However, others
support the view that empathy is a multifaceted construct, consisting of several sub-constructs
(Preston & de Waal, 2002).
Empathy refers to the ability to understand and share others’ emotional states
(Mu et al., 2008). For example, if someone is happy we get happy too, and if someone suffers
from pain, we suffer too. Importantly, one does not confuse the feelings of another with one’s
own feelings. Empathy is not to be confused with emotion contagion, which is a state in
which feelings are shared, but the self-other distinction is not present. Emotion contagion is
commonly present in babies, where this distinction is not yet developed (Singer & Klimecki,
2014). It is assumed that emotion contagion is the foundation of empathy, and that its function
is on the one hand on a phylogenetic level to provide a link between humans and other
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species, and on the other hand on an ontogenetic level between adults and children (de Wall,
2008).
When someone experiences negative emotions, the observer often experiences
compassion, or more commonly referred to as sympathy. In this state, one does not share the
feeling of suffering but rather experiences a warm and caring feeling of concern. This is
accompanied by a motivation to help the other, a so called prosocial motivation (Singer &
Klimecki, 2014). In sympathy, one feels for and not with the other. Another reaction to the
suffering of others is empathic/personal distress. In this case, the observer perceives the
suffering as self-oriented, and reacts with aversion to the situation. The observer has a strong
desire to withdraw from the situation in order to avoid this negative feeling (Singer &
Klimecki, 2014).
As in the state of sympathy or empathic distress, empathy does not concern only
negative feelings. On the other hand, empathy can occur regardless of the valence of the
feelings, either positive or negative (Singer & Klimecki, 2014)
The ability to experience empathy is not unique to humans; it seems to derive
from antecedents in other species as well as rodents (Panksepp & Panksepp, 2013). There is
also compelling evidence that other animals than humans possess the ability to experience
sympathy; for example, some animals consolidate each other when losing a fight (de Waal,
2008).
It is of great social importance to possess the ability to feel empathy for others.
If we encounter a person who seems to lack this ability, they are usually considered to be
either socially impaired or socially deviant (Bruneau, Jacoby, & Saxe, 2015). The ability to
experience empathy is one of our most fundamental skills. It requires both emotional and
cognitive functioning in the sense that one needs to be able to understand the thought and
feelings of another, as well as take part in their emotions (Rameson, Morelli, & Lieberman,
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2012). Therefore, many scientists differentiate between affective, or emotional empathy, and
cognitive empathy (Ruckmann et al., 2015). Affective empathy refers to the sharing of
feelings with others whereas cognitive empathy is the ability to understand others’ emotions,
which is strongly connected to theory of mind (Eres & Molenberghs, 2013).
For example, affective empathy is most often associated with activity in the
insula, whereas cognitive empathy is, on the other hand, connected to activity in the
midcingulate cortex and the adjacent dorsomedial prefrontal cortex (MCC/dmPFC). These
findings provide validation for the hypothesis that empathy consists of several components. In
other words, affective and cognitive empathy correlate with different neural and structural
activities (Eres, Decety, Louis, & Molenberghs, 2015).
Affective empathy is typically referred to as the conscious experience of others’
emotional states, which requires a self-other distinction, and an understanding of the origin of
the emotion. In other words, this component of empathy reflects one’s subjective experience
of other beings’ emotions. Affective empathy differs from emotion contagion and mimicry,
which are automatic responses and do notnecessarily require the distinction between self and
other. It is also different from sympathy and empathic concern since they don’t have to
contain the sharing of emotions. Affective empathy has, on the other hand, been thought of as
an umbrella term encompassing emotion contagion, mimicry, sympathy and empathic concern
(Eres et al., 2015).
Cognitive empathy refers to the ability to understand others’ motivation
(Decety, 2011). Some researchers refer to cognitive empathy as Theory of Mind (ToM)
(Mazza et al., 2015), although others make a distinction between empathy and ToM. Kanske,
Böckler, Trautwein and Singer (2015) investigated a novel functional magnetic resonance
imaging (fMRI) paradigm called EmptaTom in order to reveal clearly separable neural
networks for empathy and ToM. For the experience of empathy, there seemed to be a network
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in the anterior insula, whereas for ToM, a network was found in the ventral temporoparietal
junction. EmptaTom allows separation of the affective and cognitive routes to understanding
others (Kanske et al., 2015).
The understanding and experience of another person’s pain, as well as other
emotional states, is a characteristic of empathy. Many studies on empathy have been carried
out with specific focus on pain. The brain areas involved with the direct experience of pain
are also involved with empathy for the pain of others (Decety, Michalska, & Akitsuki, 2008)
which makes the study of pain important for the understanding of empathy.
Pain serves a function from an evolutionary perspective because it warns the
subject and, in turn, the surrounding beings. The behavioral expressions as well as empathy
for pain are necessary for us to be able to help and give care to the suffering individual (Craig,
2004). Facing a person that experiences pain can give rise to a variety of responses, ranging
from ignoring to helping (Goubert et al., 2005). Usually, the sharing of the feeling of pain is
an automatic response, although behavioral responses are distinguished by cognitive factors
such as perspective taking, and emotion regulation such as motivation (Eres & Molenberghs,
2013).
In this review, there will be a presentation of the similarities and differences
between the direct experience of pain and empathy for another person’s pain. The aim is to
explore what happens in the brain of a person who observes another person suffering from
pain in contrast to the direct experience of pain. First there will be a brief overview of the
phenomenon of empathy and its neural correlates. Then there will be an overview of the
physiology of pain and the different pathways and neural structures involved with painful
experience. This section will provide an understanding of the direct experience of pain, from
peripheral stimuli to the fundamental neural processes giving rise to a painful experience.
Thereafter, the essay will focus specifically on empathy for pain. Here prominent research in
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this field will be presented, including the disparity of empathy for pain in different neural
deficits, genders and ages. Moreover, this section will also examine the factors which underlie
how empathy for pain can be altered and regulated.
Empathy
Neural Correlates of Empathy
A growing number of studies indicates that understanding and sharing of
emotions of others depends on a recruitment of the same neural structures both associated
with our own experience and when observing others experience the same thing (Rameson &
Lieberman., 2009). The simulation theory of empathy suggests that our understanding of
another being’s emotions and thought is gained when we use our own minds as a model
(Rameson & Lieberman, 2009) and the discovery of mirror neurons and shared networks have
been considered to support this notion (Gallese & Goldman, 1998). In the following, the
phenomenon of mirror neurons will be presented as well as an overview on its current debate.
Mirror neurons. In 1992, an interesting discovery was made that showed that
specific neurons in a monkey’s brain fire when the monkey reaches for objects, as well as
when it observes someone else perform the same action. This phenomenon was revealed by
recording specific cells with electrodes inserted into the brain of the monkey. The monkey
was then presented with a peanut and when it reached for this, the recorded cell fired. In
another experiment, the monkey observed the experimenter reach for a peanut instead, which
caused the very same cell in the monkey’s brain to fire. What makes these neurons special is
that there is no distinction between the monkey’s own performance of an action and the mere
observation of another performing the very same action (De Waal, 2009). This discovery has
been said to be as important to psychology as the discovery of DNA to biology, and the fact
that this was done in monkeys further shows that empathy is not unique to humans (De Waal,
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2009). However, the existence of mirror neurons is not proven to be the same as empathy, and
the role they play in empathy is not clear yet (Lamm & Majdandžić, 2015). There are
differing opinions among scientists as to whether mirror neurons correlate with action
understanding or if they are simply a part of the action. In the same way, the activity in shared
networks involved with empathy for pain could either be thought of as a route to
understanding the feelings of others or as a sign of it (Lamm & Majdandžić, 2015).
The hypothesis that mirror neurons reflect action understanding has been
heavily questioned and Hickok (2009) puts forward arguments against this proposal. He states
that “a motor representation cannot distinguish between the range of possible meanings
associated with such an action” (Hickok, 2009, p. 1240). This means that an action consists of
several elements and that the intentions and components of an action could be many.
Therefore, because of this range of possible meanings and ways to achieve a goal, there has to
be a clear distinction between the goal and the specific motor actions necessary to achieve it.
The hypothesis that action understanding is a consequence of a similar activity in our own
brain would then be false, either because mirror neurons do not code actions, or because
motor representations are not the basis of action understanding (Hickok, 2009).
The brain areas that are associated with mirror neurons are collectively called
the “mirror system” (Baron-Cohen, 2011). As mentioned earlier, these areas are active when
an individual performs an action as well as when observing someone else performing the very
same action. For ethical reasons, it has been somewhat difficult to establish which areas the
human mirror system might contain, although it has been suggested that it involves the IFG,
the inferior parietal lobule (IPL) and the inferior parietal sulcus (IPS) Although there is no
direct evidence that mirror neurons reflect empathy (Lamm & Majdandžić, 2015), the mirror
system is implicated in mimicry and emotion contagion. For example, when someone else
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yawns and one involuntarily yawns too, these areas are activated. Actions such as these,
which are called “mimetic” actions, occur automatically (Baron-Cohen, 2011).
The empathy circuit. The neuroscientific understanding of empathy has
increased quickly, thanks to a growing number of studies (mostly carried out with fMRI
because of its availability and precision) which have enabled us to associate different brain
regions with components of empathy (Lamm, & Majdandžić, 2015). Frequently, the brain
areas involved with empathy have been referred to as the empathy circuit (e.g. Baron-Cohen,
2011)
The medial prefrontal cortex (MPFC) is referred to as a centrality that processes
social information. It is also involved with the ability to compare one’s own perspective with
another’s. The dorsal part of this region (dMPFC) is associated with thinking about the
thoughts and feelings of other people, as well as our own. The ventral part (vMPFC) is on the
other hand involved with merely the thoughts of the self and one’s own mind, rather than
someone else’s (Baron-Cohen, 2011). It has also been hypothesized by Damasio that this area
has to do with the processing of emotional valence in actions. Damasio proposes a so called
“somatic marker”, which is the emotional outcome of an action and the thing that makes us
tend to repeat only the actions that we associate with positive emotions (Damasio, Everitt, &
Bishop, 1996). Also, this theory is supported by findings demonstrating that the vMPFC is
one of the regions involved with the control of mood-related behaviors (Lim, Janssen,
Kocabicak, & Temel, 2015). The vMPFC is one of the regions that show abnormally low
activation in people with low empathy (Baron-Cohen, 2011) and it also seems to be involved
with cognitive empathy (Shamay-Tsoory, Aharon-Peretz, & Perry, 2009).
The orbitofrontal cortex (OFC) is a part of the vMPFC. When OFC is damaged,
patients lose their social judgement which affects the social behavior. Further, OFC
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impairments are often associated with empathy dysfunction and psychopathy (e.g., Baron-
Cohen, 2011; Shamay-Tsoory et al., 2009).
Adjacent to the OFC is the frontal operculum (FO). The adjacent part of the FO
is, together with the anterior insula, involved with the processing of other’s negative emotions
and negative experiences such as pain. They are also associated with positive feelings of
another, in that these two areas map the bodily feelings of others into the internal state of the
observer (Jabbi, Swart, & Keysers, 2007). Also, the posterior insula has been suggested to
support an early convergence of sensory and affective processing (Morrison, Löken, &
Olausson, 2010).
Moving on to the area located inferior to the FO, called the inferior frontal gyrus
(IFG), this area is important in the processing of emotional faces (Baron-Cohen, 2011).
Moreover, the IFG is involved with affective empathy and if damaged, this capacity is heavily
disturbed (Shamay-Tsoory et al., 2009).
The middle cingulate cortex (MCC) plays a role in empathy in that it is
associated with bodily aspects of self-awareness (Baron-Cohen, 2011). Together with the
anterior insula (AI) it is activated during the experience of pain as well as when observing
others in pain (Baron-Cohen, 2011; Singer et al., 2004). Damage to these regions can disrupt
the ability to recognize emotions such as happiness, disgust and pain (Baron-Cohen, 2011).
The temporo-parietal junction (TPJ) seems to be important to ToM, in that it is
associated with the judgement of other’s intentions and beliefs (Saxe & Kanwisher, 2003). It
is also involved with the self-other distinction (Schulte-Rüther et al., 2008).
Superior temporal sulcus (STS) is associated to empathy because of animal
studies revealing neurons in STS have been found to respond when the animal observes
someone else’s gaze (Baron-Cohen, 2011). Further, this area seems to be involved with the
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processing of biological motion and facial expressions of others. The STS might also play a
role in emotional perspective taking. (Schulte-Rüther, Markowitsch, Shah, Fink & Piefke,
2008).
The last brain structure that has been concluded to be a part of the empathy
circuit is the amygdala (Baron-Cohen, 2011). The amygdala is associated with emotional
learning and regulation processing (Wager, Davidson, Hughes, Lindquist, & Ochsner, 2008).
It is also involved with empathic regulation towards the emotional pain of others such as
deliberate control of self-focused distress (Bruneau et al., 2015)
The abovementioned areas are the major structures implicated in empathy
(Baron-Cohen, 2011) and moreover the most important regions to this thesis. In the following,
it will be discussed how their activity may be represented in the observer of a person suffering
from pain, as well as in the suffering individual. Keeping our current knowledge of empathy
in mind, some differences between these activities and the consequences of how impairments
to some of these areas may affect empathy will be presented.
Pain
Theories of Pain
Physical pain includes a number of events such as tissue damage, visceral
unpleasantness, arousal, a change in the direction of attention, negative affect as well as a
desire to withdraw from similar experiences. Most of these features are nonspecific when
looked at individually, in that they do not occur merely as a reaction to pain. Therefore,
nociceptive pain does not represent pain as such; rather, it representsthe combination of
several features (Zaki, Wager, Singer, Keysers, & Gazzola, 2016). This combination of events
is referred to as nociceptive pain, which is the first hand-experience of physical pain (Zaki et
al., 2016). The term derives from nociceptors; the kind of receptors that are activated when
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non-neural tissue is damaged. In the skin, there are different nerve fiber endings, which
possess different functions. These fibers are axons of cells and neurons that project to the
dorsal root ganglia (DRG) or the trigeminal ganglia (TG) (Chuquilin, Alghalith, & Fernandez,
2016). The different types of fibers are categorized by means of their diameter and
myelination. It is the small fibers with little or no myelination that are responsible for the
sensation of pain, and that are called nociceptors (Chuquilin et al., 2016). C-fibers, which are
unmyelinated and slowly conducting, are often polymodal and respond to noxious thermal
mechanical stimuli (Julius & Basbaum, 2001). Also, many C-fibers respond to chemical
noxious stimuli such as acid or capsaicin. Aδ-fibers are, on the other hand, slightly myelinated
and therefore conduct faster than C-fibers (Weiss et al., 2008). They respond to intense
mechanical stimuli, and can alternate in how they are affected by tissue damage or heat
(Julius & Basbaum, 2001).
It has been assumed that Aδ-fibers mediate so called “first” pain, which is rapid,
acute and sharp pain, whereas C-fibers are thought to mediate “second” pain, namely the
delayed, more diffuse and dull pain (Julius & Basbaum, 2001). In relation to selective noxious
stimulation of tiny parts of the skin, C-fiber stimulation was strongly associated with activity
in the right frontal operculum and the anterior insula, whereas stimulation of Aδ-fibers was
not. Based on current knowledge of these structures, it has been further suggested (Weiss et
al., 2008) that C-fibers might be engaged in homeostatic and interoceptive functions in
another way than Aδ-fibers, “producing a signal of greater emotional salience” (p. 1372).
Information from the nociceptors travels to different parts of the brain via different pathways
from the spinal cord (Apkarian, Bushnell, & Schweinhardt, 2013).
Historically, the study of pain has resulted in differing theories about its origins
and characteristics. Specificity theory stated that pain is a specific modality, such as vision or
hearing. According to this theory, pain receptors in the body tissue project to a specific center
EMPATHY FOR PAIN 15
in the brain, where it is processed (Melzack & Wall, 1996). However, it has been argued that
clinical, physiological and psychological experiences do not support the idea of a direct
transmission from stimulus and sensation to the brain (Melzack & Wall, 1967). For example,
there is evidence from patients and cases in which the subject experiences severe pain even
though the pain stimulus is mild, as well as when subjects do not experience pain at all despite
powerful painful stimuli. Moreover, there have been difficulties in locating fibers that always
respond to harmful stimuli (Melzack & Wall, 1967).
As a reaction to specificity theory, a number of alternative theories came to
existence, which can be grouped under the term pattern theory. These ‘pattern theories’
suggested that there are no specific pain receptors; rather, the experience of pain arises from
an intense stimulation of nonspecific receptors, which in turn creates a nerve impulse pattern
(Melzack & Wall, 1996). However, most of the pattern theories failed to acknowledge the
existence of highly specialized fibers and receptors (Melzack & Wall, 1967). The proposal of
the so-called gate control theory of pain marked a significant change in thinking and
theorizing about pain
Gate control theory of pain.
The gate control theory of pain by Melzack and Wall (1967; 1996) contributed
to the understanding of pain by its emphasis on central neural mechanisms. It forced the
medical and biological sciences to consider the brain as an active system that modulates
inputs (Melzack & Katz, 2004). The theory suggests a “gating mechanism” which mediated
modulation of pain information and this proposal received greatreception and research
emerged to support or disprove it.
The human spinal cord includes gray matter that forms three pair of horns; the
dorsal, lateral and ventral horns. Out of these three, it is the dorsal horns that have been shown
to be important for the processing of pain in that they receive information from primary
EMPATHY FOR PAIN 16
afferent axons such as nociceptors that respond to for example tissue-damaging stimuli from
the skin, muscle joints and viscera (Todd & Koerber, 2013). The gate control theory states
that inhibitory interneurons in the dorsal horn are important to the control of incoming
sensory information and are thereafter sent to the brain (Todd & Koerber, 2013). The
foundation of the gate control theory rests upon the fact that impulses from peripheral
stimulation are transmitted to the following three spinal cord systems: substantia gelatinosa
fibers in the dorsal horn; dorsal column fibers that project to the brain; and the so called ‘T
cells’ in the dorsal horn (Melzack & Wall, 1967). The substantia gelatinosa consists of small
and densely packed cells that together form an extension of the spinal cord. In the dorsal horn,
nerve impulses from peripheral fibers are thought to be modulated. Thus, the substantia
gelatinosa functions as the gate control system. The modulation of the afferent patterns further
activates T cells, which in turn gives rise to the activation of neural mechanisms which
comprise an “action system”. In this system, the perception of the painful stimuli is processed,
as well as the response to it. The gate control system in the substantia gelatinosa is affected by
the so called “central control trigger” which contains of the afferent patterns in the dorsal
column. The central control trigger causes the activation of selective brain processes,
influencing how the nerve impulses will be modulated within the gate control system
(Melzack & Wall, 1967).
The gate control theory suggests that the experience of pain is a consequence of
an interaction between the three abovementioned systems (Melzack & Wall, 1967). Since the
theory was proposed the role of the dorsal horn has been intensively studied; however, there is
limited knowledge within this field. What is known is that the dorsal horn consists of four
neuronal components; primary afferent axons, interneurons, projection neurons and
descending axons. Altogether, these components make up for the response to and modulation
of sensory and nociceptive information and the transmission of this information to various
EMPATHY FOR PAIN 17
parts of the brain and other spinal segments (Todd & Koerber, 2013). The next section will
focus on pain and how the impulse projects from the onset of harmful stimuli to the brain,
giving rise to the overall experience of pain.
Pain Pathways
The multidimensional experience of pain implies different pathways involving
different structures in the brain. In order to clarify the broadness of pain, we need an
understanding of these pathways and how they comprise several brain areas, resulting in the
many components of the pain sensation.
The pathway most commonly associated with pain (Dostrovsky & Craig, 2013)
is called the spinothalamic projection because pain related information is sent directly from
the spinal column to the thalamus.
The information can also be sent from the thalamus to homeostatic control
regions in the medulla and brain stem. Spinal input to the brain stem affects the spinal and
forebrain activity, which in turn might influence pain experience (Dostrovsky & Craig, 2013).
When the information is sent to the brain stem it is called spinobulbar projection. This
pathway is involved with the integration of nociceptive activity with processes associated
with homeostasis and behavior. However, direct projections to the hypothalamus and ventral
forebrain are also possible.
In addition to the spinothalamic and spinobulbar projections, which are
considered to be the two most prominent pathways, there are also indirect pathways that seem
to be related to pain. These are the post-synaptic dorsal column (PSDC) system and the
spinocervicothalamic (SCT) pathway. The PSDC and SCT pathways both originate from cells
in the spinal dorsal horn and signals project from the brain stem to the forebrain (Dostrovsky
& Craig., 2013).
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The discovery of the abovementioned pathways expands our knowledge about
the multidimensionality of pain because it shows that the experience of pain is due to several
factors and projections and relates to different neural structures. However, it is important to
keep in mind that this experience is due to the activity in many brain regions simultaneously.
As Dostrovsky and Craig state, it is the “…constellation of activity across the entire brain that
must constitute the basis for the conscious experience of pain.” (Dostrovsky & Craig, 2013, p.
196).
Neural Correlates of Pain
Information from nociceptors projects via different pathways to the brain,
mostly through the thalamus, which is interconnected to different structures within the
cerebral cortex (Dostrovsky & Craig, 2013). When talking about the neural correlates of pain
one often refers to the involved brain structures as a “pain matrix” (Baron-Cohen, 2011;
Singer et al., 2004). The pain matrix consists of the following areas: the primary
somatosensory cortex (SI), the secondary somatosensory cortex (SII), insular regions, the
anterior cingulate cortex (ACC), the movement-related areas such as the cerebellum and
supplementary motor areas and the thalamus (Singer et al., 2004). The ACC and the MCC are
associated with the affective-motivational aspects of pain and also with functions linked to
emotional experiences (Lamm & Majdandžić, 2015).
Especially important to the study of pain is the thalamus. The lateral thalamus is
associated with discriminative pain, whereas the medial thalamus is involved with the
motivational aspects of pain. However, it is important to keep in mind that the sensation of
pain does not occur within the thalamus, but its interconnection to the cerebral cortex gives
rise to this particular experience (Dostrovsky & Craig, 2013).
As noted earlier, a growing number of studies suggest that a consistent cortical
and subcortical network has been found to respond to pain in healthy subjects. Commonly, the
EMPATHY FOR PAIN 19
areas involved with this network are the SI, SII, ACC, IC, PFC, thalamus and cerebellum. It
seems that the somatosensory cortices are associated with the perception of sensory features
such as location and duration of pain, and the limbic and paralimbic regions such as the ACC
and IC are associated with the emotional and motivational aspects of pain (Apkarian et al.,
2013).
Empathy for Pain
Neural Correlates of Empathy for Pain
When one is experiencing empathy for another’s pain, this involves a complex
process in which the sensory and emotional qualities of vicarious pain are extracted and then
mapped onto neural substrates which may or may not be those that are activated in the direct
experience of pain (Betti & Aglioti, 2016). However, some studies indicate that it is only the
affective component of the pain matrix that is involved with empathy for pain (Singer et al.,
2004) which suggests that it is only the emotional representation of pain that is shared
between the observer and the sufferer (Avenanti, Paluello, Bufalari, & Aglioti, 2006).
One of the first studies with focus on the social neuroscientific study of empathy
for pain was carried out by Singer et al. (2004). By using fMRI, the authors investigated
which brain regions were active when participants experienced pain, as well as when
observing another person suffering from pain. This provided evidence for pain-related
responses and also confirmed that empathic experience does not involve activation of the
entire pain matrix, but only the regions associated with the affective dimension of the
experience of pain. The study was carried out with the help of 16 couples, based on the
assumption that couples are likely to empathize with each other. The authors scanned the
female partners with fMRI and exposed either them, or their partners, to pain using an
electrode attached to the back of their right hands (Singer et al., 2004). A mirror was placed
so that the female could see both her and her partner’s hand. Stimulation was either low (no
EMPATHY FOR PAIN 20
pain) or high (painful) and presenter to either the female or the male. When females were
presented to pain (“self” condition), there was an increased activity in the following brain
areas: contralateral SI/MI, bilateral SII with peak activation in contralateral posterior insula
extending into SII, bilateral mid and anterior insula, ACC, right ventrolateral and mediodorsal
thalamus, brainstem, and mid and right lateral cerebellum (Singer et al., 2004). These regions,
which make up for the pain matrix have been associated with painful stimuli in several studies
(Bruneau et al., 2015; Jacoby, Bruneau, Koster-Hale, & Saxe, 2016; Lamm, Decety, &
Singer, 2011). When the male partners were presented with painful stimuli (“other”
condition), the following brain regions showed activation in the female’s brains: ACC (more
specifically, the anterior and posterior rostral zones), the AI bilaterally with an extension into
inferior prefrontal cortex, cerebellum and the brainstem. These activations show that some of
the areas in the pain matrix are activated also when observing another person suffering from
pain. However, the absence of activity in the somatosensory cortex is one distinct factor that
differentiates empathic pain from physical pain, in which there is activity in this region. Also,
in the “other” condition, there were observed activations in the ventral and dorsal visual
stream, including bilateral fusiform cortex, lateral occipital and right posterior superior
temporal sulcus, the left inferior parietal cortex, and the left superior frontal cortex. (Singer et
al., 2004) Results from this study showed that there was an overlapping neural activation in
cingulate and insular cortices during the direct experience of pain as well as when
empathizing with the pain of others. In other words, empathy recruits similar neural networks
as the direct experience of the emotion one is showing empathy for (Singer et al., 2004).
Because of these similarities between the neural activations for self-and-other-related
experiences, it has been suggested that the ability to experience empathy is partially based
upon the processing of our own emotions (Kanske et al., 2015).
EMPATHY FOR PAIN 21
Shared networks. As noted earlier, empathizing with another person’s feelings
has been shown to activate the neural networks that are also related to the direct experience of
the very same feeling (Betti & Aglioti, 2016). In order to study empathy on a neuroscientific
level, researchers often study these shared neural networks in relation to pain. This is mostly
done by either presenting participants with painful stimulation to their bodies, or by
presenting them with pictures or cues that indicates that another person experiences pain. The
most common way to measure the brain activity in such studies is by using fMRI. Thereafter,
comparisons are made between the first-hand experience of pain and the observation of
another person suffering from pain. These kinds of studies have repeatedly shown that shared
neuronal networks exist (Singer & Klimecki, 2014).
When empathizing with another individual suffering from pain, we talk about
empathic pain (Zaki et al., 2016). The overlap between nociceptive and empathic pain has
been noticed and investigated for decades and research has shown that specific brain
structures such as the anterior insula (AI) and parts of the cingulate cortex (CC) are typically
activated both in the experience of nociceptive pain and empathic pain (e.g., Lamm et al.,
2011; Singer et al., 2004). However, this activation of AI and CC might be represented in
other psychological states as well, such as attention or arousal (Singer, Critchley, &
Preuschoff, 2009). Hence, there is currently a debate among researchers on whether the
similarities between nociceptive pain and empathic pain suggest shared pain-specific
processes or if these findings are a consequence of incorrect reverse inference (Zaki et al.,
2016). This would mean that neural activity is incorrectly associated with a certain cognitive
process.
Even if pain is the most widely used and common way to study empathy, similar
studies have also shown similar paradigms of a shared network in field of touch, disgust, taste
and social rewards. A shared network has been observed in the somatosensory cortex in
EMPATHY FOR PAIN 22
relation to vicarious neutral touch, and in the medial orbitofrontal cortex in relation to
vicarious pleasant touch. In the study of shared social rewards, a shared network has been
found in the ventral striatum, and in the study of taste and disgust there is a shared network in
parts of the AI (Singer & Klimecki, 2014).
Somatosensory system. In the experience of empathy for pain, both affective
and sensorimotor pathways are involved. However, the question of what role the
somatosensory cortex (SI) plays in this process remains unanswered (Betti & Aglioti, 2016).
For example, experimental paradigms may affect the activation in the somatosensory cortex
since it is involved with touch and some experiments show visual cues where models are
being touched (Baron-Cohen, 2011; Lamm et al., 2011). Also, experiments in which
participants are presented to abstract visual cues that indicate the pain of another, did not
show significant activation of SI and SII (Singer et al., 2004). Although SI is mostly
considered to be involved with somatic processing, it also seems to play an important role in
complex cognitive functions such as social cognition. Activity in the somatosensory structures
during observation of the emotional state of others could provide the observer with a somatic
reflection of what that particular emotional state may feel like (Bufalari, Aprile, Avenanti, Di
Russo, & Aglioti, 2007).
Bufalari et al. (2007) used somatosensory-evoked potentials (SEPs) together
with EEG to investigate if observing a model suffering from pain or tactile stimuli modulates
neural activity in the somatic system of the observer. SEPs are a noninvasive, non-painful
way to assess somatosensory system functioning and were in this experiment obtained by
electrical stimulation of the right median nerve at the participants’ wrists. Attendants were
presented to video clips where models were experiencing pain or tactile stimuli. Activations
in the primary somatosensory cortex (SI) correlated with the intensity but not the
unpleasantness of the pain and touch. The results from this study suggest that neural activity
EMPATHY FOR PAIN 23
in SI is not only involved with the actual experience of pain and touch, but it also seems to be
modulated by the observation of others’ bodily sensations (Bufalari et al., 2007).
Factors Influencing Empathy for Pain
There are several factors that can influence to what degree one feels empathy for
another individual’s pain, such as the affective link or similarity between observer and
sufferer (Loggia, Mogil, & Bushnell, 2008), the age (Bandstra, Chambers, McGrath, &
Moore, 2011) and gender (Christov-Moore et al., 2014) of the observer and the context in
which the empathy is experienced. Factors such as these will be explained and discussed in
terms of behavioral and neural mechanisms in this following section.
Age. Already by the age of 5-6 years, it is very clear that children are able to
recognize and identify pain in others, and refinements of this ability continue through to early
adulthood (Deyo, Prkachin, & Mercer, 2004). However, little is known about how and when
children develop or express empathy for another individual’s pain (Bandstra et al., 2011). The
empathic response first emerges as a reaction of personal distress and is often accompanied
with self-focused behavior such as self-soothing. As the child matures, the control of the own
emotions typically becomes better and the focus on the needs of an individual in distress
becomes greater (Bandstra et al., 2011). In a test where 120 children between the ages of 18
and 36 months were presented with simulations of an adult’s pain and sadness respectively,
their empathy-related behaviors were investigated. The results in this study indicated that
children tended to be more sensitive to others’ sadness, in which they became distressed and
showed prosocial behavior. When presented with others’ pain, the children were more likely
to continue playing. However, behaviors associated with empathic concern and personal
distress emerged in both situations. It was speculated that the reason for a reduced reaction to
the pain stimulus might be a consequence of the children not regarding the pain of others as
EMPATHY FOR PAIN 24
threatening to their selves. Further, this finding has been suggested to be due to the frequency
of painful events that occur in childhood, thus leading the child to become inured to observing
others in pain (Bandstra et al., 2011). Older children were more likely to react to the pain
stimulus with empathic concern and less likely to react with personal distress than younger
children. In the sadness condition, this age difference was however not present, suggesting
that the developmental course of empathy for pain and empathy for sadness are different
(Bandstra et al., 2011).
In one study investigating the development of empathy, fMRI was used to scan
and compare children and adults (Decety & Michalska, 2010). Participants in the age of 7-40
years old were presented with animations depicting painful and non-painful conditions.
Results from this study showed that children and adults have similar patterns of brain activity
when observing other people in pain: in the ACC, somatosensory cortex, and periaqueductal
gray (PAG) and the insula. Despite this, there are some important age differences in the neural
activity associated with empathic pain. For example, the amygdala and the posterior insula are
developed much earlier in childhood than other structures such as the dorsal and lateral
vMPFC, which are slower to mature and later on become specialized for the evaluation of
social stimuli (Decety & Michalska, 2010). Also, different parts of the prefrontal cortex (PFC)
mature at different rates, indicating that the development of affective processing from
childhood to adulthood is associated with reduced activity in the limbic affect processing
systems, whereas there is an increased activity in other prefrontal systems (Decety &
Michalska, 2010). Further, older adults seem to be more sensitive than younger people to the
intentional harm of others (Chen, Chen, Decety, & Cheng, 2014). The empathic response in
the mPFC and STS does not change with age, although, the activity in the AI and anterior
mid-cingulate cortex in response to others’ pain has been shown to decline with age. This
EMPATHY FOR PAIN 25
finding indicates that the neural response associated with affective empathy lessens with age,
whereas the response to perceived agency is preserved (Chen et al., 2014).
Gender. Sex differences in empathy-like behaviors have been reported in
nonhuman animals such as primates and rodents and suggest that females possess greater
levels of empathy in at least some species (Christov-Moore et al., 2014). It has been shown
that there are human gender differences in empathy for pain, in that both the short-latency
empathic response and the long-latency empathic response to a stimuli depicting someone
suffering from pain differs (Han, Fan, & Mao, 2008). There also seems to be a gender
difference in the activation of the MCC and the AI in relation to observing others in pain.
When men observe someone they do not like or consider fair, they generally show less
activity in these areas than when they like the suffering person (Singer et al., 2006).
Females have been shown to have higher emotional responsiveness and
mirroring responses to the suffering of others, and they are also better at recognizing emotions
(Christov-Moore et al., 2014). Further, it has been suggested that females tend to show more
prosocial and altruistic behavior. In other words, females seem to be show higher affective
empathy for other’s pain. In contrast, in terms of cognitive empathy, it has been suggested
that males show more utilitarian behavior than females, accompanied by a greater recruitment
of areas that are associated with cognitive control and cognition (Christov-Moore et al.,
2014).
In a study where gender differences in the neural networks associated with
empathy were investigated (Schulte-Rüther, Markowitsch, Shah, Fink, & Piefke, 2008), fMRI
was used to scan subjects while they were presented with different emotion expressing faces.
The participants were asked to either focus on their own emotional response to the presented
picture, or to evaluate the emotional state that the observed face expressed. Females rated
EMPATHY FOR PAIN 26
their own response higher than males. The females’ brain activity in this task involved a
stronger activation in the right inferior frontal cortex and STS whereas the males showed a
stronger activity in the left TPJ. Since the TPJ is associated with the self-other distinction, this
suggests that males rely more on this distinction than females. In the task were the
participants were asked to evaluate the observed face’s emotional state, females showed an
increased activity of the right inferior frontal cortex in contrast to males. Taken together,
results from this study suggest that females recruit more brain areas containing mirror neurons
than males do and that these gender differences may indicate different strategies in how own
emotions are processed in response to others (Schulte-Rüther et al., 2008).
Empathy for non-human entities. The ability for humans to empathize with
other animals in a similar way as with their own offspring has been suggested to depend on an
instinct of nurturance (Prguda & Neumann, 2014). Using fMRI, Mathur, Cheon, Harada,
Scimeca and Chiao (2016) investigated whether the neural reactivity associated with empathy
for pain was different when directed to humans than to non-human entities. They measured
neural activity when subjects were presented with visual scenes depicting people, animals and
nature in either negative or neutral conditions. The same brain regions that increased in
activity while subjects were experiencing empathy for other people were active when they
observed animals and nature in harmful conditions (e.g. dorsal anterior cingulate cortex,
bilateral anterior insula). These findings suggest that the activity within these areas is not
specific to humans only, but also when empathizing with other animals and the nature
(Mathur et al., 2016). However, empathy for humans and other animals has shown to be
facilitated by the perceived phylogenetic similarity between the object and subject (Prguda &
Neumann, 2014). Stronger phasic skin conductance response (SCR) and subjective ratings of
empathic experience have been associated with human participants observing the suffering of
phylogenetically similar species than more different animals. The subjective ratings did not
EMPATHY FOR PAIN 27
differ much when subjects were presented to suffering humans, non-human primates and
quadruped mammals. On the other hand, the arousal and subjective experience of empathic
emotions were rated as much lower when observing birds suffering from pain (Prguda &
Neumann, 2014). Also, SCR showed that participants were more emotionally aroused and
directed more attention toward stimuli depicting suffering humans than to non-human
primates. This response was further decreased when participants were presented to stimuli of
suffering quadruped mammals, and even lower in the bird stimuli. This supports the idea that
phylogenetic similarity plays an important role in empathy for the pain of others (Prguda &
Neumann, 2014).
Empathy among caregivers. In medical practice, pain is most commonly
defined by its pathological cause. In cases where a physical cause is not found, the patients’
pain is often thought to be imaginary (Ojala et al., 2015). In order to investigate “invisible”
chronic pain, Ojala et al. (2015) studied the contact between patients and care givers. The
patients report that their experience of pain is often underrated or denied. Further, many of
these patients have problems trusting and believing in their helpers and they also have mental
health problems together with the painful experience. Even though there is a current
recommendation to treat chronic pain as a biopsychosocial experience, it is often thought to
be a symptom of an underlying disease (Ojala et al., 2015). In other words, too little empathy
among caregivers may have devastating effects on the health of patients. However, failure to
help patients suffering from chronic pain may also have negative effect on the caregivers. Too
much empathy can cause the helper to suffer more than usual with the patient, which can
result in a desire to withdraw from this kind of work. Caregivers with too much empathy tend
to continue with treatments even if they are not helping, or even worse, if they risk damaging
the patient (Breivik, 2015).
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Another factor that might have an effect on how caregivers react to a patient’s
pain is their individual experience. Nursing students without clinical experience tend to rate
mild pain as more painful and urgent than students with clinical experience (Chan &
Hamamura, 2015). A possible explanation to this would be that students without this learning
have not observed patients expressing their pain before and therefore overestimated mild pain.
Also, students with clinical experience might have observed patients who reported their pain
as higher than it actually was perceived, thus leading the student to rate mild pain as less
urgent. Further, these students could be more used to seeing patients suffering from different
levels of pain, and therefore grade mild pain as less urgent to treat in contrast to severe pain
(Chan & Hamamura, 2015).
Racial bias. Research has shown that the brain response of an individual
observing another one in pain can be different depending on the race of the observer and the
suffering person. If the two are of the same ethnicity, there is a higher activity in the ACC and
the bilateral insula, than if they are of different ethnicities (Cao, Contreras-Huerta, McFadyen,
& Cunnington, 2015). In conditions where the observer and the sufferer are of different
ethnicities, the ACC activity in the observer increases in line with the amount of contact
between them. However, this increase of activation is not dependent on the closeness or the
relationship between the two, rather, the amount of experience they have of each other in an
every-day life context. This evidence supports the idea that racial bias changes in line with an
increased experience and contact with new immigrants (Cao et al., 2015).
It has been suggested that two variants of a certain oxytocin receptor gene
polymorphism are associated with racial bias in brain activities that are linked to implicit
attitude and altruistic motivation (Luo et al., 2015). Racial bias of empathy is however not
inevitable (Sheng & Han, 2012). In a study where Chinese adult subjects observed Asian and
Caucasian faces reflecting neutral or painful expressions respectively, the racial bias was
EMPATHY FOR PAIN 29
manipulated. In order to identify the bias, participants were asked to make race judgments on
the different faces presented, while detecting the brain activity with event-related potentials
(ERP). The subjects’ ratings of the pain intensity in the pictures as well as their own reported
self-unpleasantness was higher for pain than for neutral stimuli, while there was no significant
difference between ratings of the effect of facial expression between Asian and Caucasian
faces (Sheng & Han, 2012). However, when presented to same-race faces expressing pain,
there was an increased neural response at 128-188 ms after the onset of stimuli. This effect
did not occur when subjects observed other-race painful stimuli. In the following experiments,
it was found that the racial bias was eliminated when participants were paying attention to the
observed individual’s feeling of pain. Also, including the other-race individual in their own
team for competitions had the same effect of an increased neural response (Sheng & Han,
2012).
Racial bias in empathy for the pain of others can cause pain treatment
disparities. For example, it has been shown that African Americans receive lower quality pain
treatment than European Americans (Drwecki, Moore, Ward, & Prkachin, 2011). A solution
to this problem might be to induce the empathy in healthcare by interventions, which in turn
would decrease the differences in provided pain treatment. This proposal rests upon the
finding that perspective-taking can reduce pain treatment bias by upwards of 55% (Drwecki et
al., 2011).
Important to keep in mind is that the results related to racial bias in empathy for
the suffering of other might change over time and that it might also depend on the level and
quality of contact between races (Cao et al., 2015).
Atypical Aspects of Empathy for Pain
EMPATHY FOR PAIN 30
As noted earlier, the ability to experience empathy is socially important
(Bruneau et al., 2015). In this following section, some atypical forms of empathic abilities or
impairments will be discussed.
Synaesthesia for pain. In synaesthesia for pain, one does not only empathize
with the pain of another, but also experiences the observed or imagined pain as if it was one’s
own. At face value, the neural mechanisms that seem to be involved with this kind of
synaesthesia include so called “mirror systems”. This means that the same systems are active
both when the synaesthete observes someone else experiencing pain as well as when the
synaesthete directly experiences pain. Fitzgibbon, Giummarra, Georgiou-Karistianis, Enticott
and Bradshaw (2010) propose that synaesthesia for pain might be the result of painful and/or
traumatic experiences that causes disinhibition in the mirror system that underlies empathy for
pain. (Fitzgibbon et al., 2010b) This phenomenon is common in individuals who have lost a
limb and the synaesthetic pain experience is triggered specifically in response to other
individuals’ pain (Fitzgibbon et al., 2010a).
One study investigated the motor cortical excitability in lower-limb amputees
who experienced synaesthetic pain (Fitzgibbon et al., 2012). By using transcranial magnetic
stimulation (TMS) administered to the motor cortex, it was found that changes in the motor
cortical excitability did not appear to contribute to the synaesthetic pain experience. If the
sensorimotor mirror system disinhibition is involved with synaesthetic pain, it may not be
driven by motor cortical excitability. Rather, other mechanisms could underlie this
phenomenon, such as the amount of attention directed towards the experience of pain. Paying
attention to the somatic cause of the observed pain may trigger activity in the somatosensory
cortex and therefore result in the observer’s painful sensation (Fitzgibbon et al., 2012).
Finally, changes in cortical excitability in other brain regions should be investigated. Since the
EMPATHY FOR PAIN 31
dorsolateral PFC, ACC, insula and the parietal lobule are involved with pain processing, they
could be of more use to look at in this study (Fitzgibbon et al., 2012).
However, the role of mirror neurons in synaesthesia for pain remains unclear
and more research is needed to investigate whether both the affective and sensory areas of the
pain matrix is activated when pain synaesthetes experiences empathic pain (Fitzgibbon et al.,
2010b). Importantly, related to the ongoing debate on what role mirror neurons have in
empathy (Lamm & Majdandžić, 2015), factors underlying the synaesthetic experience of pain,
such as the affective link between observer and sufferer needs to be determined (Fitzgibbon et
al., 2010b).
Psychopathy. It is well established that people with psychopathy lack the ability
to feel affective arousal, affective empathy and caring for others’ well-being. As noted earlier,
psychopathy is associated with impairments in the OFC (Baron-Cohen, 2011).
Since perspective taking has been shown to give rise to empathy and concern in
healthy subjects, Decety, Chen, Harenski and Kiehl (2013) investigated to what extent
perspective taking could affect the empathic ability in psychopaths. In their study, they used
fMRI to scan subjects classified as high, intermediate and low psychopaths while they were
presented with stimuli depicting body parts being injured and simultaneously instructed to
adopt a perspective where they imagined their own and the others’ perspective. In the
condition where they self-imagine condition, the subjects with high psychopathy showed
activity in the anterior insula, anterior MCC, supplementary motor area, IFG, SI and the right
amygdala, which reflects a typical response associated with empathy for pain. In the other-
imagine condition, participants showed an atypical response in the AI and the amygdala with
a connectivity with the OFC. This atypical connectivity points further to the empathy deficit
in psychopathy (Decety et al., 2013).
EMPATHY FOR PAIN 32
According to Lishner, Hong, Jiang, Vitacco and Neumann (2015), the proposed
link between psychopathy and impairments in affective empathy is emotional callousness.
This was discovered in a study where psychopathy, narcissism and borderline personalities
were tested for emotional contagion and empathic concern. There was little evidence of a
consistent negative association between most measures of psychopathic, narcissistic and
borderline traits and affective empathy change scores. However, there was an exception in
callousness among psychopaths, which revealed consistent negative associations with
affective empathy change scores. When presented to neutral stimuli, psychopaths’ callousness
was associated with lower emotional contagion of sadness, anger and fear (Lishner et al.,
2015).
Huntington’s disease. Individuals suffering from Huntington’s disease (HD)
have been shown to have impairments in their ability to recognize emotions in others and they
also show deficits in empathy (Baez et al., 2015). In an experiment, manifest HD patients,
first-degree asymptomatic relatives and healthy control subjects completed three different
tests; two of emotion recognition, one of empathy for pain. In the first task, participants were
presented with morphed faces illustrating six basic emotions (happiness, surprise, disgust,
sadness, fear and anger) and instructed to identify the emotion as soon as it was recognized.
The second test, called the Emotion Evaluation Test (EET), participants were presented with
short videotaped vignettes were actors illustrated a basic emotion. This presentation was
followed by a forced-choice task in which the participants were to choose the viewed emotion
(Baez et al., 2015). In the Empathy for Pain Task (EPT), participants were presented with 24
animated situations, either depicting intentional or accidental harm to another being, or
neutral situations. The subjects were asked to press a button as soon as they understand the
situation and were then instructed to answer questions about the presented situation and its
context. Accuracy, reaction time and ratings were measured during the experiment. The
EMPATHY FOR PAIN 33
results from this study showed that both HD patients and their first-degree asymptomatic
relatives had an impaired ability to recognize negative emotions in faces. Also, HD patients’
ability to understand the intentionality of others’ actions was compromised. These results
suggest that impairments and difficulties in emotion recognition might be a potential
biomarker of HD onset and progression (Baez et al., 2015).
Asperger’s syndrome. It has also been shown that people with Asperger
syndrome (AS) may have a reduced empathic response to the pain of others (Minio-Paluello,
Baron-Cohen, Avenanti, Walsh, & Aglioti, 2009). Subjects were presented with video clips
that showed model hands being penetrated with a needle in a specific muscle. Simultaneously,
the response of the same hand muscles was recorded in the subjects with motor-evoked
potentials (MEP). The MEP did not show any reduction of the amplitude in AS participants,
whereas this reduction was observed in healthy control subjects (Minio-Paluello et al., 2009).
Also, TMS revealed that there was no neurophysiological modulation of the AS participants’
corticospinal system when presented with the video clips, in contrast to controls. Further, AS
participants represented the pain of others in relation to their self-oriented arousal when
observing the videos. The lack of embodiment of other’s pain suggests that people with AS
have empathic difficulties (Minio-Paluello et al., 2009).
However, much research on AS patient’s empathic abilities has been said to
focus on cognitive empathy or self-report questionnaires, and not on affective empathy
(Dziobek et al., 2008). This limitation in the study of empathy among AS individuals is
suggested to derive from a lack of appropriate instruments that could dissociate cognitive
empathy from affective empathy. In a study using a so called Multifaceted Empathy Test
(MET) that measures both components of empathy, greater ecological validity could be
assessed than with self-report questionnaires because the test included photorealistic stimuli
(Dziobek et al., 2008). In this study, AS patients and control subjects were presented with a
EMPATHY FOR PAIN 34
series of photographs, mostly depicting emotionally charged situations. The cognitive
empathy was assessed when the participant was asked to infer the mental states of the
observed individual in the photograph, whereas the affective empathy was assessed by the
subjects’ ratings of their emotional reactions to the photographs. Results showed that AS
patients had difficulties in cognitive, but not in affective aspects of empathy. This suggests
that the amount of concern for the suffering of others is not different in AS patients than
control subjects (Dziobek et al., 2008).
Post-traumatic stress disorder. Research has shown that individuals suffering
from post-traumatic stress disorder (PTSD) have impairments in affective empathy, but not in
cognitive empathy (Mazza et al., 2015). This result was found in a study in which PTSD
patients and healthy control subjects performed a modified version of the MET and were
simultaneously scanned with fMRI. Participants were instructed to answer three questions
about the presented photographs depicting negative, positive or neutral emotions. First, they
were asked to infer the valence of the mental state of the depicted individuals. Thereafter,
implicit affective empathy was measured when participants were asked to rate the level of
arousal experienced when presented to a picture. The explicit affective empathy was assessed
when participants rated the empathic concern they felt for the depicted individuals (Mazza et
al., 2015). During the measurement of cognitive empathy, there was an increased activation in
the right medial frontal gyrus and the left inferior frontal gyrus in PTSD patients, but not in
controls. In the implicit affective empathy, PTSD patients showed a greater activity in the left
palladium and the right insula, whereas control subjects showed an increased activity in the
right inferior frontal gyrus. The explicit affective empathy showed a reduced activity in the
left insula and the left inferior frontal gyrus in the PTSD patients. These results indicate that
there is a dissociation between emotional and affective empathy in PTSD patients (Mazza et
al., 2015).
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Regulation of Empathy for Pain
Repeated exposure to others’ pain can have devastating effects on the observing
individual, such as burnout, personal distress or compassion fatigue (Decety, Yang, & Cheng,
2010). Therefore, the ability to regulate empathy for pain is necessary, particularly among
health care professionals who often encounter suffering individuals. As mentioned earlier, too
much empathy among care givers may have negative effects on their wellbeing as well as the
treatment of the patients (Breivik, 2015). Research has shown that physicians rate the
intensity and unpleasantness of pain in others as lower than control subjects, and that the
neural response is different in the sense that physicians down-regulate the sensory processing
when witnessing others in pain (Decety et al., 2010). This regulation has been suggested to
have many beneficial outcomes because it allows physicians to focus on the treatment and
assistance for their patients instead of counterproductive feelings of alarm and fear (Decety et
al., 2010).
Empathy for pain has also been shown to be regulated by transcranial direct
current stimulation (tDCS) to the dorsolateral prefrontal cortex (DLPFC) (Rêgo et al., 2015;
Wang, Wang, Hu, & Li, 2014). Both left and right DLPFC seem to be involved with self-
regulation and general affective modulation, and the right DLPFC has been associated with
the evaluation of valence and arousal of other’s pain (Rêgo et al., 2015). The understanding
that tDCS can modulate empathy for pain leads to the suggestion that this method could be
used as a potential tool for modulating diseases that are accompanied with deficits in empathy
(Wang et al., 2014).
There is equivocal evidence on the role of the amygdala in regulation of pain
empathy. This might be because some experiments are focused on the emotional pain of
others, while others investigate the physical pain of others (Bruneau et al., 2015). A recent
EMPATHY FOR PAIN 36
study has shown that the amygdala is involved with the deliberate regulation of empathy
towards the emotional pain of others, but not to their physical pain (Bruneau et al., 2015).
Moreover, regulation of empathy for emotional pain activates regions in the LPFC and
deactivates the amygdala, whereas regulation of empathy for physical pain activates largely
distinct regions such as AI, and had no effect on amygdala (Bruneau et al., 2015).
The neural underpinnings of pain experience have been shown to be influenced
by top-down attention, in the sense that the experience of pain becomes less remarkable when
attention is drawn to something else than the noxious stimuli (Gu & Han, 2007). Gu and Han
investigated whether the neural substrates of empathy for pain are also modulated by similar
top-down mechanisms. Participants were scanned with fMRI and simultaneously presented to
pictures or cartoons of hands that were exposed to either painful or neutral stimulation. In one
condition, the subjects were asked to evaluate the intensity of pain perceived by the model,
while in the other condition, they were to count the number of hands on the display. In
contrast to the neutral condition with counting, the rating of pain intensity in painful pictures
or cartoons induced increased activity in ACC/paracingulate and the right middle frontal
gyrus (Gu & Han, 2007). There was also a difference in how the stimuli were presented: for
pictures in the pain-related stimuli, there was an increased activation in the inferior frontal
cortex bilaterally and the right insula/putamen. When presented with cartoons, there was an
increased activation in the left parietal cortex, the postcentral gyrus, and the occipitotemporal
cortex. Also, the activity in the ACC was stronger for the pictures than for the cartoons. None
of the aforementioned brain regions were active when participants were asked to count the
number of hands presented to them. The results of this study show that empathy for pain
seems to be modulated by top-down attention as well as the contextual presentation of stimuli
(Gu & Han, 2007).
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Empathy Affects Pain Perception
We have now seen that many factors can affect and modulate the empathic
experience for another individual’s pain. From the sufferer’s perspective, empathy directed
towards oneself may affect the pain experience (Hurter, Paloyelis, Williams, & Fotopoulou,
2014).
The pain experience has been shown to be influenced by the social context as
well as by empathy from a partner (Hurter et al., 2014). The higher the empathy from
subjects’ partners was the higher the intensity of pain was rated. However, pain tolerance and
facial expression was not influenced by empathy from another. These results indicate that the
belief that a partner is feeling empathy for one’s pain leads the subject to experience the pain
intensity as higher, even though behavioral response and communication between partners did
not affect the pain sensation to the same degree. Hurter et al. (2014) proposes that empathy
from a partner may cause the subject to focus on their pain experience because the empathic
response from the other signals a painful value (Hurter et al., 2014).
The degree to which an observer experiences empathy for another person’s pain
depends on the affective link between the two (Sessa & Meconi, 2015). Individuals that have
high empathy for another person in pain tend to rate their own pain experience as more
intense when presented to similar harmful stimuli as the observed person. If the empathy
towards the other is lower, then the observer’s pain experience will be rated as lower too
(Loggia et al., 2008). By manipulating the empathy towards the other, the experience of pain
can be modulated. Since this finding was compared to neutral stimuli as well, this seems to
imply that empathy itself alters the perception of pain, and not necessarily the observation of
pain behaviors (Loggia et al., 2008).
Further, studies have shown that subjects rate their pain as higher when
EMPATHY FOR PAIN 38
observing painful scenes (such as models suffering from pain, pictures of wounds) than when
observing neutral scenes. This might be the result of the degree of empathy that the subject
experiences, but other explanations are also possible. First, the mere observation of someone
in pain is likely to induce an overall negative mood, which in itself has been shown to
increase the intensity of pain perception (Rainville, Bao, & Chrétien, 2005). Second, the
response can be autonomic as a result of classical conditioning, in that the image of a wound
has been associated with the experience of pain throughout our lives (Rainville et al., 2005).
The third factor that can give rise to the empathic pain response is that imitation can be
elicited by observation of another being suffering from pain. This so called social modelling
could be one explanation for differences in pain ratings in some of the studies in this field
(Loggia et al., 2008).
Conclusions
Empathy is for most of us a well-known construct, yet it is hard to define.
Consisting of several subcomponents and factors, a growing body of research, often carried
out with fMRI, begins to bring clarity to the concept of empathy. Compelling evidence
indicates a shared neural network for the empathic experience of others’ emotions and the
direct experience of the very same emotion.
Much research on empathy has focused on pain and the shared networks
associated with individuals empathizing with the pain of others. Specifically, activity in brain
structures such as the AI and parts of the CC are typically associated both with nociceptive
and empathic pain. Importantly, these structures might also be associated with attention or
arousal as well.
In one of the first studies on empathy for pain (Singer et al., 2004), it was found
that only the brain areas in the pain matrix associated with the affective dimension were active
EMPATHY FOR PAIN 39
in individuals observing others in pain. Results from several studies indicate that the ACC,
AI, PFC, cerebellum and brainstem are activated in both the physical and the empathic pain
experience. However, an absence of activity in the somatosensory cortex in empathic pain
could be one factor that differentiates empathy for pain and physical pain. Recent research has
questioned the role of the somatosensory cortex in empathic pain, since this area is associated
with touch. In some studies on the subject, activation in this area has been shown, although
one possible explanation to this might be that the experimental paradigms influence the
individual since the observed individual experiences the sense of touch.
This thesis has further discussed the different factors that might give rise to
different empathic experiences and abilities. Evidence show that empathy is refined with age
and also that brain regions such as the amygdala, insula and the PFC mature at different rates,
which indicates that the development of affective processing is associated with a reduced
activity in the limbic areas and an induced activity in other prefrontal systems. There are also
gender differences in the ability to experience empathy for pain. For example, females have a
higher emotional responsivity and mirroring responses, and they also show more prosocial
behavior than men. On the other hand, men seem to show more utilitarian behavior and recruit
areas associated with cognition to a greater extent than females. To what degree humans
emphasize with others is dependent on the phylogenetic similarity and relationship between
observer and sufferer. If the two are of different races, there is a higher activity in the ACC
and in the bilateral insula of the observer, when seeing the other being exposed to painful
stimuli.
While some individuals possess an unusually high empathic ability, others seem
to lack this capacity. For example, psychopaths have impairments in their affective empathy
while individuals with Asperger’s syndrome have difficulties in cognitive, but not in affective
EMPATHY FOR PAIN 40
empathy. The fact that empathic abilities and impairments can differentiate in such a degree
between people supports the notion that empathy is a multidimensional construct.
Whether the overlap between nociceptive and empathic pain is due to shared
neural networks or just, perhaps, the result of an incorrect reverse inference, is a question still
unanswered. Also, some studies suggest that the perception of others’ pain may reflect the
processing of threats, rather than being an automatic pro-social response (Ibáñez et al., 2011).
This means that empathy for pain might in fact be a signal of danger, due to the possible
threat that we recognize in others’ expressions.
In order to investigate the consistency of previous findings suggesting that the
direct experience of pain as well as empathy for pain is underpinned by the same neural
substrates, meta-analyses of several previous studies have been carried out (Lamm, et al.,
2011). The findings confirmed a shared network in the bilateral anterior insular cortex and in
the medial/anterior cingulate cortex. This network is referred to as a core network underlying
empathy for pain, and was activated together with other brain regions; depending on the
different types of experiments they analyzed (Lamm et al., 2011). For example, participants
viewed pictures of various body parts in painful situations activated brain areas in the
observer that are associated with action understanding, such as the inferior parietal/ventral
premotor cortices. When the participant on the other hand was presented to abstract visual
information about the suffering of another, areas associated with inferring and representing
mental states of self and other (such as the precuneus, ventral medial prefrontal cortex,
superior temporal cortex and temporo-parietal junction) were instead more active (Lamm et
al., 2011). Furthermore, it was found that somatosensory areas were only activated in the
picture-based experiments. This meta-analytic investigation led to the conclusion that social
neuroscience paradigms provide reliable and accurate insights into the field of empathy
(Lamm et al., 2011).
EMPATHY FOR PAIN 41
Many of the studies reported in this review have utilized fMRI. It is commonly
acknowledged that because of the vagueness and imprecision in the hemodynamic response
and the fact that the neural activity is only indirectly measured results in a limitation in the use
of fMRI (Lamm & Majdandžić, 2015). Also, fMRI data is almost always analyzed on group
level after each individual’s data has been smoothed which may lead to misinterpretations
about activations that might in fact not be present at individual levels (Fitzgibbon et al.,
2010b). At a general level, these limitations should always be borne in mind in interpretation
of research findings, and this applies to the current review. For example, in a study in which it
was investigated to what degree cingulate areas involved with the processing of self- and
other-pain shared the same neural basis, this problem was emphasized (Morrison & Downing,
2007). In this study, participants were scanned with fMRI as they experienced either physical
pain or empathic pain. It was found that the group-averaged data showed overlapping activity
in the cingulate and clear activation peaks for physical and empathic pain. Importantly, not all
individuals showed this overlap of activity, which indicated the problem with analyzing group
data and not individual data (Morrison & Downing).
Another problem in using fMRI is its coarse spatial resolution. Each voxel
covers thousands of neurons, which means that possible differences in firing and interaction
patterns are not detectable with fMRI. Other measuring techniques, such as EEG and MEP-
TMS also have this kind of problem, since these scan many neurons at a time (Lamm &
Majdandžić, 2015). The abovementioned limitations imply a difficulty in deciding what role
shared activations play in empathy. More fine-grained resolution in combination with a
multivariate imaging analysis method that detects information rather than activation would be
a possible solution to this problem (Lamm & Majdandžić, 2015).
The study of empathy for pain has improved our knowledge in the field
significantly. Since it has been observed that there are neurological and biological differences
EMPATHY FOR PAIN 42
in empathy in humans, this might also help us to widen our understanding of behavioral and
psychological differences. However, the research still needs to be expanded. The importance
of this field rests upon potential treatments to empathic dysfunctions and others in need of an
empathic response such as patients suffering from “invisible” chronic pain. One question that
needs to be answered is what role the somatosensory system has in the experience of empathy
for the pain of another. Could potential activity in this area be due to experimental paradigms,
or does this activity reflect something else? Further, individual differences need to be
evaluated and compared to group differences. Also, the role of mirror neurons in empathy
needs further investigation, such as other techniques to measure empathy and its many facets.
While pain is an interesting method for studying empathy, more research should
be carried out on other aspects of empathy. For example, there has been little focus on the
positive emotions within the construct of empathy. Future studies will hopefully contribute to
the field with potential explanations to when, how and why we experience empathy for
others’ pain as well as why this ability differentiates among individuals and contexts. Also,
the cognitive neuroscience of empathy for pain needs to be complemented with the work from
other academic disciplines such as psychological and evolutional research and philosophical
theories. This is necessary because neuroscience cannot explain the entire phenomenon of
empathy for pain; other factors such as the emotional and experiential components need to be
investigated from different perspectives.
EMPATHY FOR PAIN 43
References
Apkarian, A. V., Bushnell, M. C., & Schweinhardt, P. (2013). Representation of pain in the
brain. Wall and Melzack’s textbook of pain, 6, 111-128.
Avenanti, A., Paluello, I. M., Bufalari, I., & Aglioti, S. M. (2006). Stimulus-driven
modulation of motor-evoked potentials during observation of others' pain. Neuroimage,
32(1), 316-324. doi:10.1016/j.neuroimage.2006.03.010
Baez, S., Herrera, E., Gershanik, O., Garcia, A. M., Bocanegra, Y., Kargieman, L., ... &
Ibanez, A. (2015). Impairments in negative emotion recognition and empathy for pain
in Huntington's disease families. Neuropsychologia, 68, 158-167. doi:
10.1016/j.neuropsychologia.2015.01.012
Bandstra, N. F., Chambers, C. T., McGrath, P. J., & Moore, C. (2011). The behavioural
expression of empathy to others’ pain versus others’ sadness in young children. Pain,
152(5), 1074-1082. doi: 10.1016/j.pain.2011.01.024
Baron-Cohen, S. (2011). Zero degrees of empathy: A new theory of human cruelty.
Penguin UK.
Betti, V., & Aglioti, S. M. (2016). Dynamic construction of the neural networks
underpinning empathy for pain. Neuroscience & Biobehavioral Reviews, 63, 191-206.
doi:10.1016/j.neubiorev.2016.02.009
Breivik, H. (2015). Invisible pain–Complications from too little or too much empathy
among helpers of chronic pain patients. Scandinavian Journal of Pain, 6, 31-32. doi:
http://dx.doi.org/10.1016/j.sjpain.2014.09.004
Bruneau, E. G., Jacoby, N., & Saxe, R. (2015). Empathic control through coordinated
interaction of amygdala, theory of mind and extended pain matrix brain regions.
NeuroImage, 114, 105-119. doi: http://dx.doi.org/10.1016/j.neuroimage.2015.04.034
Bufalari, I., Aprile, T., Avenanti, A., Di Russo, F., & Aglioti, S. M. (2007). Empathy for
pain and touch in the human somatosensory cortex. Cerebral Cortex, 17(11), 2553
2561. doi: 10.1093/cercor/bhl161
EMPATHY FOR PAIN 44
Cao, Y., Contreras-Huerta, L. S., McFadyen, J., & Cunnington, R. (2015). Racial bias in
neural response to others' pain is reduced with other-race contact. Cortex, 70, 68-78.
doi:10.1016/j.cortex.2015.02.010
Chan, J. C., & Hamamura, T. (2015). Nursing students' assessment of pain and decision of
triage for different ethnic groups: An experimental study. Nurse education today, 35(8),
921-925. doi: http://dx.doi.org/10.1016/j.nedt.2015.04.004
Chen, Y. C., Chen, C. C., Decety, J., & Cheng, Y. (2014). Aging is associated with
changes in the neural circuits underlying empathy. Neurobiology of aging,35(4), 827
836. doi: 10.1016/j.neurobiolaging.2013.10.080
Christov-Moore, L., Simpson, E. A., Coudé, G., Grigaityte, K., Iacoboni, M., & Ferrari, P.
F. (2014). Empathy: gender effects in brain and behavior. Neuroscience &
Biobehavioral Reviews, 46, 604-627. doi: 10.1016/j.neubiorev.2014.09.001
Chuquilin, M., Alghalith, Y., & Fernandez, K. H. (2016). Neurocutaneous disease:
Cutaneous neuroanatomy and mechanisms of itch and pain. Journal of the American
Academy of Dermatology, 74(2), 197-212. doi: 10.1016/j.jaad.2015.04.060
Craig, K. D. (2004). Social communication of pain enhances protective functions: a
comment on Deyo, Prkachin and Mercer (2004). Pain, 107(1-2), 5-6. doi:
10.1016/S0304-3959(03)00264-1
Damasio, A. R., Everitt, B. J., & Bishop, D. (1996). The somatic marker hypothesis and
the possible functions of the prefrontal cortex [and discussion]. Philosophical
Transactions of the Royal Society of London B: Biological Sciences, 351(1346), 1413-
1420. doi: 10.1098/rstb.1996.0125
Decety, J. (2011). Dissecting the neural mechanisms mediating empathy. Emotion Review,
3(1), 92-108. doi: 10.1177 /1754073910374662
Decety, J., Chen, C., Harenski, C., & Kiehl, K. A. (2013). An fMRI study of affective
perspective taking in individuals with psychopathy: imagining another in pain does not
evoke empathy. Frontiers in human neuroscience, 7, 489. doi:
10.3389/fnhum.2013.00489
EMPATHY FOR PAIN 45
Decety, J., & Michalska, K. J. (2010). Neurodevelopmental changes in the circuits
underlying empathy and sympathy from childhood to adulthood. Developmental
science, 13(6), 886-899. doi: 10.1111/j.1467-7687.2009.00940.x
Decety, J., Michalska, K. J., & Akitsuki, Y. (2008). Who caused the pain? An fMRI
investigation of empathy and intentionality in children. Neuropsychologia, 46(11),
2607-2614. doi: 10.1016/j.neuropsychologia.2008.05.026
Decety, J., Yang, C. Y., & Cheng, Y. (2010). Physicians down-regulate their pain empathy
response: an event-related brain potential study. Neuroimage, 50(4), 1676-1682. doi:
10.1016/j.neuroimage.2010.01.025
De Waal, F. B. (2008). Putting the altruism back into altruism: The evolution of empathy.
Annu. Rev. Psychol., 59, 279-300.
De Waal, F. (2009). The age of empathy. New York, NY: Harmony.
Deyo, K. S., Prkachin, K. M., & Mercer, S. R. (2004). Development of sensitivity to facial
expression of pain. Pain, 107(1), 16-21. doi:10.1016/S0304-3959(03)00263-X
Dostrovsky, J. O., & Craig, A. D. (2013). Ascending projection systems. Wall and
Melzack's textbook of pain, 6, 182-197.
Drwecki, B. B., Moore, C. F., Ward, S. E., & Prkachin, K. M. (2011). Reducing racial
disparities in pain treatment: The role of empathy and perspective-taking. Pain, 152(5),
1001-1006. doi: 10.1016/j.pain.2010.12.005
Dziobek, I., Rogers, K., Fleck, S., Bahnemann, M., Heekeren, H. R., Wolf, O. T., &
Convit, A. (2008). Dissociation of cognitive and emotional empathy in adults with
Asperger syndrome using the Multifaceted Empathy Test (MET). Journal of autism and
developmental disorders, 38(3), 464-473. doi: 10.1007/s10803-007-0486-x
Eres, R., Decety, J., Louis, W. R., & Molenberghs, P. (2015). Individual differences in
local gray matter density are associated with differences in affective and cognitive
empathy. NeuroImage, 117, 305-310. doi: 10.1016/j.neuroimage.2015.05.038
Eres, R., & Molenberghs, P. (2013). The influence of group membership on the neural
correlates involved with empathy. Frontiers in human neuroscience, 7.
EMPATHY FOR PAIN 46
Fan, Y., & Han, S. (2008). Temporal dynamic of neural mechanisms involved with
empathy for pain: an event-related brain potential study. Neuropsychologia, 46(1), 160
173. doi:10.1016/j.neuropsychologia.2007.07.023
Fitzgibbon, B. M., Enticott, P. G., Bradshaw, J. L., Giummarra, M. J., Georgiou
Karistianis, N., Chou, M., & Fitzgerald, P. B. (2012). Motor cortical excitability and
inhibition in acquired mirror pain. Neuroscience letters, 530(2), 161-165. doi:
10.1016/j.neulet.2012.09.036
Fitzgibbon, B. M., Enticott, P. G., Rich, A. N., Giummarra, M. J., Georgiou-Karistianis,
N., Tsao, J. W., ... & Bradshaw, J. L. (2010).(a) High incidence of ‘synaesthesia for
pain’in amputees. Neuropsychologia, 48(12), 3675-3678.
doi: 10.1016/j.neuropsychologia.2010.07.029
Fitzgibbon, B. M., Giummarra, M. J., Georgiou-Karistianis, N., Enticott, P. G., &
Bradshaw, J. L. (2010).(b) Shared pain: from empathy to synaesthesia. Neuroscience &
Biobehavioral Reviews, 34(4), 500-512. doi: 10.1016/j.neubiorev.2009.10.007
Gallese, V., & Goldman, A. (1998). Mirror neurons and the simulation theory of mind
reading. Trends in cognitive sciences, 2(12), 493-501. doi:10.1016/S1364
6613(98)01262-5
Goubert, L., Craig, K. D., Vervoort, T., Morley, S., Sullivan, M. J. L., de CAC, W., ...
& Crombez, G. (2005). Facing others in pain: the effects of empathy. Pain, 118(3),
285-288. doi:10.1016/j.pain.2005.10.025
Gu, X., & Han, S. (2007). Attention and reality constraints on the neural processes of
empathy for pain. Neuroimage, 36(1), 256-267. doi:10.1016/j.neuroimage.2007.02.025
Han, S., Fan, Y., & Mao, L. (2008). Gender difference in empathy for pain: an
electrophysiological investigation. Brain research, 1196, 85-93.
doi:10.1016/j.brainres.2007.12.062
Hickok, G. (2009). Eight problems for the mirror neuron theory of action understanding in
monkeys and humans. Journal of cognitive neuroscience, 21(7), 1229-1243.
doi: 10.1162/jocn.2009.21189
EMPATHY FOR PAIN 47
Hurter, S., Paloyelis, Y., Williams, A. C. D. C., & Fotopoulou, A. (2014). Partners'
empathy increases pain ratings: effects of perceived empathy and attachment style on
pain report and display. The Journal of Pain, 15(9), 934-944.
doi: 10.1016/j.jpain.2014.06.004
Ibáñez, A., Hurtado, E., Lobos, A., Escobar, J., Trujillo, N., Baez, S., ... & Decety, J.
(2011). Subliminal presentation of other faces (but not own face) primes behavioral and
evoked cortical processing of empathy for pain. Brain research, 1398, 72-85.
doi: 10.1016/j.brainres.2011.05.014
Jabbi, M., Swart, M., & Keysers, C. (2007). Empathy for positive and negative emotions in
the gustatory cortex. Neuroimage, 34(4), 1744-1753.
doi:10.1016/j.neuroimage.2006.10.032
Jacoby, N., Bruneau, E., Koster-Hale, J., & Saxe, R. (2016). Localizing Pain Matrix and
Theory of Mind networks with both verbal and non-verbal stimuli. NeuroImage, 126,
39-48. doi: 10.1016/j.neuroimage.2015.11.025
Julius, D., & Basbaum, A. I. (2001). Molecular mechanisms of nociception. Nature,
413(6852), 203-210. doi:10.1038/35093019
Kanske, P., Böckler, A., Trautwein, F. M., & Singer, T. (2015). Dissecting the social brain:
Introducing the EmpaToM to reveal distinct neural networks and brain–behavior
relations for empathy and Theory of Mind. Neuroimage, 122, 6-19.
doi: 10.1016/j.neuroimage.2015.07.082
Lamm, C., Decety, J., & Singer, T. (2011). Meta-analytic evidence for common and
distinct neural networks associated with directly experienced pain and empathy for
pain. Neuroimage, 54(3), 2492-2502. doi: 10.1016/j.neuroimage.2010.10.014
Lamm, C., & Majdandžić, J. (2015). The role of shared neural activations, mirror neurons,
and morality in empathy–A critical comment. Neuroscience Research, 90, 15-24.
doi:10.1016/j.neures.2014.10.008
Lim, L. W., Janssen, M. L., Kocabicak, E., & Temel, Y. (2015). The antidepressant effects
of ventromedial prefrontal cortex stimulation is associated with neural activation in the
medial part of the subthalamic nucleus. Behavioural brain research, 279, 17-21.
doi: 10.1016/j.bbr.2014.11.008
EMPATHY FOR PAIN 48
Lishner, D. A., Hong, P. Y., Jiang, L., Vitacco, M. J., & Neumann, C. S. (2015).
Psychopathy, narcissism, and borderline personality: A critical test of the affective
empathy-impairment hypothesis. Personality and Individual Differences, 86, 257-265.
doi:10.1016/j.paid.2015.05.036
Loggia, M. L., Mogil, J. S., & Bushnell, M. C. (2008). Empathy hurts: compassion for
another increases both sensory and affective components of pain perception. Pain,
136(1), 168-176. doi:10.1016/j.pain.2007.07.017
Luo, S., Li, B., Ma, Y., Zhang, W., Rao, Y., & Han, S. (2015). Oxytocin receptor gene and
racial ingroup bias in empathy-related brain activity. NeuroImage, 110, 22-31.
doi: 10.1016/j.neuroimage.2015.01.042
Mathur, V. A., Cheon, B. K., Harada, T., Scimeca, J. M., & Chiao, J. Y. (2016).
Overlapping neural response to the pain or harm of people, animals, and nature.
Neuropsychologia, 81, 265-273. doi: 10.1016/j.neuropsychologia.2015.12.025
Mazza, M., Tempesta, D., Pino, M. C., Nigri, A., Catalucci, A., Guadagni, V., ... &
Ferrara, M. (2015). Neural activity related to cognitive and emotional empathy in post-
traumatic stress disorder. Behavioural brain research, 282, 37-45.
doi: 10.1016/j.bbr.2014.12.049
Melzack, R., & Katz, J. (2004). The gate control theory: Reaching for the brain. Pain:
Psychological perspectives, 13-34.
Melzack, R., & Wall, P. D. (1967). Pain mechanisms: a new theory. Survey of
Anesthesiology, 11(2), 89-90. doi: 10.1126/science.150.3699.971
Melzack, R., & Wall, P. D. (1996). Pain mechanisms: a new theory: a gate control
system modulates sensory input from the skin before it evokes pain perception and
response. In Pain Forum (Vol. 5, No. 1, pp. 3-11). Churchill Livingstone.
doi: http://dx.doi.org/10.1016/S1082-3174(96)80062-6
Minio-Paluello, I., Baron-Cohen, S., Avenanti, A., Walsh, V., & Aglioti, S. M. (2009).
Absence of embodied empathy during pain observation in Asperger syndrome.
Biological psychiatry, 65(1), 55-62. doi: 10.1016/j.biopsych.2008.08.006
EMPATHY FOR PAIN 49
Morrison, I., & Downing, P. E. (2007). Organization of felt and seen pain responses in
anterior cingulate cortex. Neuroimage, 37(2), 642-651.
doi:10.1016/j.neuroimage.2007.03.079
Morrison, I., Löken, L. S., & Olausson, H. (2010). The skin as a social organ.
Experimental brain research, 204(3), 305-314. doi: 10.1007/s00221-009-2007-y
Mu, Y., Fan, Y., Mao, L., & Han, S. (2008). Event-related theta and alpha oscillations
mediate empathy for pain. Brain research, 1234, 128-136.
doi: 10.1016/j.brainres.2008.07.113
Ojala, T., Häkkinen, A., Karppinen, J., Sipilä, K., Suutama, T., & Piirainen, A. (2015).
Although unseen, chronic pain is real—A phenomenological study. Scandinavian
Journal of Pain, 6, 33-40. doi: http://dx.doi.org/10.1016/j.sjpain.2014.04.004
Panksepp, J., & Panksepp, J. B. (2013). Toward a cross-species understanding of empathy.
Trends in neurosciences, 36(8), 489-496. doi: 10.1016/j.tins.2013.04.009
Preston, S. D., & De Waal, F. B. (2002). Empathy: Its ultimate and proximate bases.
Behavioral and brain sciences, 25(01), 1-20.
doi: http://dx.doi.org/10.1017/S0140525X02510013
Prguda, E., & Neumann, D. L. (2014). Inter-human and animal-directed empathy: A test
for evolutionary biases in empathetic responding. Behavioural processes, 108, 80-86.
doi: 10.1016/j.beproc.2014.09.012
Rainville, P., Bao, Q. V. H., & Chrétien, P. (2005). Pain-related emotions modulate
experimental pain perception and autonomic responses. Pain, 118(3), 306-318.
doi:10.1016/j.pain.2005.08.022
Rameson, L. T., & Lieberman, M. D. (2009). Empathy: A social cognitive neuroscience
approach. Social and Personality Psychology Compass, 3(1), 94-110.
doi: 10.1111/j.1751-9004.2008.00154.x
Rameson, L. T., Morelli, S. A., & Lieberman, M. D. (2012). The neural correlates of
empathy: experience, automaticity, and prosocial behavior. Journal of cognitive
neuroscience, 24(1), 235-245. doi: 10.1162/jocn_a_00130
EMPATHY FOR PAIN 50
Rêgo, G. G., Lapenta, O. M., Marques, L. M., Costa, T. L., Leite, J., Carvalho, S., ... &
Boggio, P. S. (2015). Hemispheric dorsolateral prefrontal cortex lateralization in the
regulation of empathy for pain. Neuroscience letters, 594, 12-16.
doi: 10.1016/j.neulet.2015.03.042
Ruckmann, J., Bodden, M., Jansen, A., Kircher, T., Dodel, R., & Rief, W. (2015). How
pain empathy depends on ingroup/outgroup decisions: A functional magnet resonance
imaging study. Psychiatry Research: Neuroimaging, 234(1), 57-65.
doi: 10.1016/j.pscychresns.2015.08.006
Saxe, R., & Kanwisher, N. (2003). People thinking about thinking people: the role of the
temporo-parietal junction in “theory of mind”. Neuroimage, 19(4), 1835-1842.
doi:10.1016/S1053-8119(03)00230-1
Schulte-Rüther, M., Markowitsch, H. J., Shah, N. J., Fink, G. R., & Piefke, M. (2008).
Gender differences in brain networks supporting empathy. Neuroimage, 42(1), 393-403.
doi: 10.1016/j.neuroimage.2008.04.180
Sessa, P., & Meconi, F. (2015). Perceived trustworthiness shapes neural empathic
responses toward others' pain. Neuropsychologia, 79, 97-105.
doi: 10.1016/j.neuropsychologia.2015.10.028
Shamay-Tsoory, S. G., Aharon-Peretz, J., & Perry, D. (2009). Two systems for empathy: a
double dissociation between emotional and cognitive empathy in inferior frontal gyrus
versus ventromedial prefrontal lesions. Brain, 132(3), 617-627.
doi: 10.1093/brain/awn279
Sheng, F., & Han, S. (2012). Manipulations of cognitive strategies and intergroup
relationships reduce the racial bias in empathic neural responses. NeuroImage, 61(4),
786-797. doi: 10.1016/j.neuroimage.2012.04.028
Singer, T., Critchley, H. D., & Preuschoff, K. (2009). A common role of insula in feelings,
empathy and uncertainty. Trends in cognitive sciences, 13(8), 334-340.
doi: 10.1016/j.tics.2009.05.001
Singer, T., & Klimecki, O. M. (2014). Empathy and compassion. Current Biology, 24(18),
R875-R878. doi:10.1016/j.cub.2014.06.054
EMPATHY FOR PAIN 51
Singer, T., Seymour, B., O'Doherty, J., Kaube, H., Dolan, R. J., & Frith, C. D. (2004).
Empathy for pain involves the affective but not sensory components of pain. Science,
303(5661), 1157-1162. doi: 10.1126/science.1093535
Singer, T., Seymour, B., O'Doherty, J. P., Stephan, K. E., Dolan, R. J., & Frith, C. D.
(2006). Empathic neural responses are modulated by the perceived fairness of others.
Nature, 439(7075), 466-469. doi:10.1038/nature04271
Todd, A. J., & Koerber, H. R. (2013). Neuroanatomical substrates of spinal nociception.
Wall and Melzack’s textbook of pain, 6, 77-93.
Wager, T. D., Davidson, M. L., Hughes, B. L., Lindquist, M. A., & Ochsner, K. N. (2008).
Prefrontal-subcortical pathways mediating successful emotion regulation. Neuron,
59(6), 1037-1050. doi: 10.1016/j.neuron.2008.09.006
Weiss, T., Straube, T., Boettcher, J., Hecht, H., Spohn, D., & Miltner, W. H. (2008). Brain
activation upon selective stimulation of cutaneous C-and Aδ-fibers. Neuroimage, 41(4),
1372-1381. doi:10.1016/j.neuroimage.2008.03.047
Zaki, J., Wager, T. D., Singer, T., Keysers, C., & Gazzola, V. (2016). The Anatomy of
Suffering: Understanding the Relationship between Nociceptive and Empathic Pain.
Trends in cognitive sciences, 20(4), 249-259. doi: 10.1016/j.tics.2016.02.003