Table 1.

An overview of the main brain structures related to pain discussed in this article.

Brain region	Function in pain
Amygdala	Related to the affective-motivational dimension of pain (Neugebauer et al., 2004) as well as the modulation of nociceptive stimuli (Neugebauer, 2015). Clinical pain produces peaks of activation in the laterobasal amygdala while experimental pain is often associated with an increased signal within its superficial region (Simons et al., 2014).
Anterior cingulate cortex (ACC)	Important for cognitive and affective reactions to pain (Tracey and Mantyh, 2007; Becerra et al., 2013). Increased regional blood flow driven by pain has been mostly reported in the mid-cingulate and perigenual regions (Peyron et al., 2000). It has been suggested that the activity of the perigenual ACC would be linked to the affective reaction triggered by pain unpleasantness, while the mid-cingulate part would be related to the cognitive features (motor inhibition and response selection) of pain (Vogt et al., 1996). However, the differential pain-related activation of these two areas of the ACC has been discussed (Peyron et al., 2000).
Habenula (Hb)	Important component of the reward circuitry. This small subcortical structure regulates anxiety, pain and stress and inhibits reward under such conditions (Sartorius et al., 2010; Elman and Borsook, 2016). It promotes an inhibitory regulation to the NAc dopaminergic neurons and to the mPFC neurons (Lee and Goto, 2011). Therefore, it regulates the dopamine levels in striatum. Hb also modulates the release of other neurotransmitters related to aversive behaviors through its connections to the brainstem and basal forebrain related structures (e.g., norepinephrine-locus coeruleus; raphe nuclei-serotonin; acetylcholine-nucleus basalis of Meynert) (Elman and Borsook, 2016).
Insula	Insula activation has been consistently found in fMRI pain studies (Apkarian et al., 2005). A somatotopic representation of painful thermal stimuli has been demonstrated in the dorsal posterior insula (Brooks et al., 2005). In addition, rostral anterior insula activation has been connected to clinical pain while caudal anterior insula activity has been associated with experimental pain (Schweinhardt et al., 2006).
Nucleus accumbens (NAc)	A prominent component of the reward circuitry. A decrease in the blood oxygenated level dependent (BOLD) signal at the onset (aversive) and an increase at the offset (rewarding) of painful heat stimulus has been found in the NAc of healthy subjects (Becerra and Borsook, 2008). NAc activity in response to the offset of painful stimuli allowed the differentiation between chronic low back pain and healthy subjects at very high accuracy (Baliki et al., 2010).
Prefrontal cortex (PFC)	Involved in the cognitive-attentional aspects of pain (Peyron et al., 2000). Dorsolateral prefrontal (DLPFC) has been implicated in both pain suppression and detection (Seminowicz and Moayedi, 2017). Structural changes in the DLPFC has been demonstrated in chronic pain (Apkarian et al., 2004).
Primary (S1) and secondary (S2) somatosensory cortex	Encode the basic aspects of noxious stimuli (e.g., pain intensity, quality, location, and duration) (Peyron et al., 2000).
Reticular formation	Supraspinal control of the nociceptive transmission at the level of the laminae I, II, and V of the dorsal horn of the spinal cord. Its main components are the periaqueductal gray (PAG), the rostral ventromedial medulla (RVM), and the locus coeruleus (LC). Such regions integrate the descending pain modulatory system (Ossipov et al., 2014).
Thalamus	Primarily related to the sensory-discriminative aspects of pain. Bilateral activation during painful stimulus possibly reflects its involvement in attentional networks (Peyron et al., 2000).