Table 5.

Listing specific brain areas and their possible relation to pain, chronic pain, MDD and adverse childhood experiences. ACC, anterior cingulate cortex; adverse childhood experiences, adverse childhood experiences; MDD, major depressive disorder; PCC, posterior cingulate cortex.

Regions	Involvement of MDD, chronic pain, and adverse childhood experiences
Prefrontal cortex	Involvement in vulnerability to painful conditions (reward-motivation network and descending pain modulatory system).102 Involvement of the reward-motivation and salience networks in people with MDD.104,105 Deficit in reward sensitivity and reward anticipation in adverse childhood experiences.106,107
ACC	Individuals who are vulnerable to painful conditions may have changes in the reward-motivation and descending pain modulatory systems in the brain.102 These changes may not necessarily affect the risk of developing chronic pain, but they do play a role in how pain is perceived.103,108,126 Activated by other aversive experiences, leading to negative emotions and anxiety.108, 109, 110 MDD may have alterations in the reward-motivation and salience networks.104,105 adverse childhood experiences have been linked to a deficit in reward sensitivity and reward anticipation.106,107
Amygdala	Vulnerability to painful conditions may have changes in the descending pain modulatory system in the brain.102 They play a role in how pain is perceived.103 MDD have alterations in the reward-motivation and salience networks104,105 which can contribute to their vulnerability to painful conditions.
Hypothalamus/thalamus	Vulnerability to painful conditions (descending pain modulatory system),102 may not affect risk of developing chronic pain but is a relevant region to pain perception.103 Involvement with the MDD.104,105
Nucleus accumbens	Individuals who are at risk of experiencing painful conditions may have changes in the reward-motivation network in the brain.102 MDD may have alterations in the reward-motivation and salience networks,104,105 which can make them more susceptible to painful conditions. adverse childhood experiences have been linked to a deficit in reward sensitivity.106,107 Anhedonia, chronic pain, and depression is linked to dopamine abnormalities affected by inputs from the hippocampus. Research also suggests that childhood adversity can lead to dysfunction of the basal ganglia during reward anticipation.
Ventral tegmentum	Vulnerability to painful conditions (reward-motivation network).102 Involvement of the reward-motivation and salience networks in people with MDD.104,105 Deficit in reward sensitivity and dysfunction during reward anticipation in humans exposed to adverse childhood experiences.106,107
Hippocampus	Vulnerability to painful conditions (reward-motivation network), is a relevant region to pain perception.103 Involvement of the reward-motivation and salience networks in people with MDD.104,105 Children exposed to traumatic events have smaller hippocampus and weaker activity in that region during memory tasks.116 This is associated with difficulties in learning and memory in individuals with chronic pain.130, 131, 132 Changes in the structure of the hippocampus, which is often impacted by chronic pain, may contribute to the emergence of depression.133,134
Insula	It is an important area in regard to the perception of pain.103,108 It is activated by other negative experiences as well, leading to negative emotions and anxiety.108, 109, 110 Blunted signal in aversive stimuli in MDD. Mediates changes in the default mode network and frontoparietal network facilitating responses to salient stimuli.108,115 Increased insula activation in children exposed to violence.116, 117, 118, 119, 120, 121
Orbitofrontal cortex	It is still an area of the brain that plays a role in the perception of pain.103 MDD may have alterations in the reward-motivation and salience networks.104,105
Primary/secondary somatosensory cortex	A significant area in terms of pain.103
PCC	It is a significant area in terms of the sensation and perception of pain,103 and episodic memory retrieval.122 MDD have been found to have abnormal activity in this region, and healthy individuals who have experienced adverse childhood experiences. PCC activation may be more related to the emotional and memory-related aspects of stimuli, rather than the actual experience of pain.122