**3. Neural network for pain empathy**

With the improvements in functional brain neuroimaging, most studies have focused on activity patterns and neural networks of empathy for pain [6, 26–28].

#### **Figure 1.**

*(A) Mid-cingulate cortex (MMC) and (B) anterior insula (AI) are most impressed areas in empathy for pain studies.*

Since early functional neuroimaging studies, the revealing of the same nervous system activation in the case of first-hand pain with responses to pain in others has prompted researchers to explore empathy for the pain core. In these studies, compared with experienced vs. observed pain, experiencing pain activates more extensive regions (with a posterior gradient) than observing pain [29]. Left mid-cingulate cortex (MMC) and left anterior insula (AI) were most impressed two regions in empathy for pain studies (**Figure 1**) [28–30], and pointed regions were also activated by the physical experience of pain [28, 31, 32]. A comprehensive study systematic search from 128 functional brain imaging studies has been confirmed neural correlates of empathy has a core network comprising AI, MCC, postcentral gyrus, inferior parietal lobe, thalamus, amygdala, and brainstem (**Table 1**) [26].

Even though there was considerable overlap in networks for pain empathy and empathy for non-pain negative affective states, empathy for pain uniquely activated bilateral mid-insula and more extensive MCC [30]. Also, activated areas of empathy network showed differentiation with the type of stimuli in the brain. While the core empathy regions evoked with painful faces and pain inflictions, acute pain inflictions also activated additional regions, including medial frontal and parietal cortex [26]. A meta-analysis of neuroimaging studies on the role of visual information indicated that individuals have different activated area response to three factors: visual cues (body parts, facial expressions), visuospatial (first-person, third-person), and cognitive (self-, stimuli-, other-oriented tasks) perspectives [33]. Body-parts distinctly activated sensorimotor processing areas (superior and inferior parietal lobules, anterior insula) while facial expression distinctly involved the inferior frontal gyrus. They have concluded that pain empathy relies on a core network which is modulated by several secondary networks [33]. This second system may contribute to process depending on the visual cues available and the observer's mental state. When we consider the pain for empathy has a quite complex mood, and network, the existing of undefined secondary structures would not be surprised.

The differentiation of activated regions has also been observed in the types of empathy. Although perceptual/affective and cognitive/evaluative parts of empathy show similar neural circuitry, cognitive/evaluative paradigms activated more left MCC regions while perceptual/affective paradigms activated more right AI (**Table 2**) [34]. The studies with paracetamol show that it might decrease psychological reactivity and alter the pain empathy in healthy human subjects [35, 36]. Paracetamol was altering specifically the affective part while keeping the cognitive part of empathy largely intact in healthy subjects. These findings mean that paracetamol reduces the emotional response to other people's negative pain experiences without affecting the pain's mentalising and internalisation. Inconsistent with this, one study suggested that paracetamol increased state empathy scores with activation of paracingulate


**63**

for the pain of others [41].

**4. Conclusion**

*Empathy for Pain*

Left AI\*

*\**

**Table 2.**

*DOI: http://dx.doi.org/10.5772/intechopen.95276*

*orbital frontal cortex (OFC), anterior insula (AI).*

*Region that involved in both types of empathy.*

**Affective-perceptual empathy Cognitive empathy**

Right ACC Left OFC Right DMT Left MCC Midbrain Left DMT Right AI Left AI\*

gyrus is responsible for the processing of cognitive empathy in headache group [37]. The researchers concluded this paradigm that pain experience related adaptive brain changes might be strongly linked to the cognitive part of empathy, and targeting pain-induced empathetic neuroplasticity pathways could be a novel treatment

*The differences in regions are activated in cognitive–evaluative and affective–perceptual empathy [34].*

*Dorsal anterior cingulate cortex (dACC), anterior mid-cingulate cortex (aMCC), dorsal medial thalamus (DMT),* 

As we mentioned in pain empathy part, balancing of emotions provides us respond effectively and adaptively to the environmental factors. Otherwise, empathy could be destructive and unhelpful for us. Usually, individuals use to regulate their emotions with cognitive reappraisal. For example, a recent study demonstrated the exaggerated individuals' emotional pain empathy intensity, if the judgement of pain made after the participant's pain experiences as a cognitive bias. But, that bias disappeared when participants used reappraisal to regulate their empathy [38]. The emotion regulation, and mainly reappraisal-based downward regulation, is associated with executive control and limbic networks, namely the prefrontal cortex and the amygdala [39, 40]. A study compared activated region with fMRI for empathising with painful *vs* non-painful scenarios as well as for reappraising painful *vs* non-painful scenarios. Empathising with painful scenarios was associated with increased connectivity with the mid-cingulate and anterior cingulate cortex

Conversely, during reappraisal of painful *vs* non-painful scenarios, increased connectivity was found between the inferior frontal gyrus (IFG) and the bilateral lateral occipital cortex, as well as with the left IFG, left posterior insula and left parahippocampal gyrus. Interestingly, different regulation strategies resulted in increased connectivity with other parts of the network. Empathic watch resulted in increased connectivity with regions involved in the processing of self-pain. In contrast, reappraisal resulted in increased connectivity with regions involved in the simulation of other pain, as well as self-pain processing [42]. Activation in the left supramarginal gyrus (SMG) and the right middle frontal gyrus (MFG) was found during empathic watch only, suggesting that these two regions play a critical role and are associated with the process of feeling empathy

In line with getting raising numerous study, it could simplify the role of empathy for pain based on a matching of psychological states between the sufferer and the observer. This matching contributes to prosaically actions, affective sharing, emotion regulation, and provide to alleviating the pain and suffering of others.

strategy for the development of novel painkillers [37].

(ACC), as well as with the bilateral post-central cortex [41].

#### **Table 1.** *The neural correlates of empathy.*


*Dorsal anterior cingulate cortex (dACC), anterior mid-cingulate cortex (aMCC), dorsal medial thalamus (DMT), orbital frontal cortex (OFC), anterior insula (AI). \* Region that involved in both types of empathy.*

#### **Table 2.**

*Pain Management - Practices, Novel Therapies and Bioactives*

(**Table 1**) [26].

Since early functional neuroimaging studies, the revealing of the same nervous system activation in the case of first-hand pain with responses to pain in others has prompted researchers to explore empathy for the pain core. In these studies, compared with experienced vs. observed pain, experiencing pain activates more extensive regions (with a posterior gradient) than observing pain [29]. Left mid-cingulate cortex (MMC) and left anterior insula (AI) were most impressed two regions in empathy for pain studies (**Figure 1**) [28–30], and pointed regions were also activated by the physical experience of pain [28, 31, 32]. A comprehensive study systematic search from 128 functional brain imaging studies has been confirmed neural correlates of empathy has a core network comprising AI, MCC, postcentral gyrus, inferior parietal lobe, thalamus, amygdala, and brainstem

Even though there was considerable overlap in networks for pain empathy and empathy for non-pain negative affective states, empathy for pain uniquely activated bilateral mid-insula and more extensive MCC [30]. Also, activated areas of empathy network showed differentiation with the type of stimuli in the brain. While the core empathy regions evoked with painful faces and pain inflictions, acute pain inflictions also activated additional regions, including medial frontal and parietal cortex [26]. A meta-analysis of neuroimaging studies on the role of visual information indicated that individuals have different activated area response to three factors: visual cues (body parts, facial expressions), visuospatial (first-person, third-person), and cognitive (self-, stimuli-, other-oriented tasks) perspectives [33]. Body-parts distinctly activated sensorimotor processing areas (superior and inferior parietal lobules, anterior insula) while facial expression distinctly involved the inferior frontal gyrus. They have concluded that pain empathy relies on a core network which is modulated by several secondary networks [33]. This second system may contribute to process depending on the visual cues available and the observer's mental state. When we consider the pain for empathy has a quite complex mood, and network, the existing of undefined secondary structures would not be surprised. The differentiation of activated regions has also been observed in the types of empathy. Although perceptual/affective and cognitive/evaluative parts of empathy show similar neural circuitry, cognitive/evaluative paradigms activated more left MCC regions while perceptual/affective paradigms activated more right AI (**Table 2**) [34]. The studies with paracetamol show that it might decrease psychological reactivity and alter the pain empathy in healthy human subjects [35, 36]. Paracetamol was altering specifically the affective part while keeping the cognitive part of empathy largely intact in healthy subjects. These findings mean that paracetamol reduces the emotional response to other people's negative pain experiences without affecting the pain's mentalising and internalisation. Inconsistent with this, one study suggested that paracetamol increased state empathy scores with activation of paracingulate

**62**

**Table 1.**

Anterior insula (AI) Mid-cingulate gyrus (MCC)

Postcentral gyrus Inferior parietal lobe

*The neural correlates of empathy.*

Thalamus Amygdala Brainstem *The differences in regions are activated in cognitive–evaluative and affective–perceptual empathy [34].*

gyrus is responsible for the processing of cognitive empathy in headache group [37]. The researchers concluded this paradigm that pain experience related adaptive brain changes might be strongly linked to the cognitive part of empathy, and targeting pain-induced empathetic neuroplasticity pathways could be a novel treatment strategy for the development of novel painkillers [37].

As we mentioned in pain empathy part, balancing of emotions provides us respond effectively and adaptively to the environmental factors. Otherwise, empathy could be destructive and unhelpful for us. Usually, individuals use to regulate their emotions with cognitive reappraisal. For example, a recent study demonstrated the exaggerated individuals' emotional pain empathy intensity, if the judgement of pain made after the participant's pain experiences as a cognitive bias. But, that bias disappeared when participants used reappraisal to regulate their empathy [38]. The emotion regulation, and mainly reappraisal-based downward regulation, is associated with executive control and limbic networks, namely the prefrontal cortex and the amygdala [39, 40]. A study compared activated region with fMRI for empathising with painful *vs* non-painful scenarios as well as for reappraising painful *vs* non-painful scenarios. Empathising with painful scenarios was associated with increased connectivity with the mid-cingulate and anterior cingulate cortex (ACC), as well as with the bilateral post-central cortex [41].

Conversely, during reappraisal of painful *vs* non-painful scenarios, increased connectivity was found between the inferior frontal gyrus (IFG) and the bilateral lateral occipital cortex, as well as with the left IFG, left posterior insula and left parahippocampal gyrus. Interestingly, different regulation strategies resulted in increased connectivity with other parts of the network. Empathic watch resulted in increased connectivity with regions involved in the processing of self-pain. In contrast, reappraisal resulted in increased connectivity with regions involved in the simulation of other pain, as well as self-pain processing [42]. Activation in the left supramarginal gyrus (SMG) and the right middle frontal gyrus (MFG) was found during empathic watch only, suggesting that these two regions play a critical role and are associated with the process of feeling empathy for the pain of others [41].

#### **4. Conclusion**

In line with getting raising numerous study, it could simplify the role of empathy for pain based on a matching of psychological states between the sufferer and the observer. This matching contributes to prosaically actions, affective sharing, emotion regulation, and provide to alleviating the pain and suffering of others.

#### *Pain Management - Practices, Novel Therapies and Bioactives*

Under the light of empathy for pain studies, it should be indicated that the neural networks of empathy for pain have not still exactly clarified yet.

Whether the underlying processing of empathy for pain/pain empathy is associated with other non-pain negative affective states still needs more investigation. This gap mentioned-above is particularly relevant for studying empathic responses in different contexts, with diverse populations (age, sex, culture, vocation, etc.) and other affective/sensory states. In the context of the crucial role of pain in the quality of life, empathy for pain deserves more experimental studies for effective pain management in people suffering intractable pain attacks. This chapter discusses not only the definition of empathy for pain, but also the importance of its brain -network correlates, and the ability to empathise with pain in others. Future studies are required for revealing the essential components of pain empathy by different pain stimuli and paradigms.

## **Author details**

Ece Ozdemir Oktem\* and Seyda Cankaya Department of Neurology, Alaaddin Keykubat University, Alanya, Turkey

\*Address all correspondence to: ece.oktem@alanya.edu.tr

© 2021 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**65**

*Empathy for Pain*

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