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

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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

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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

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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

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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

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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

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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

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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

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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).

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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

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