Highly sensitive people (HSP) were first studied and described by psychologist Aron (1996), who identified people that are high in a personality trait known as sensory-processing sensitivity (SPS). Individuals with high sensitivity exhibit abnormal reactivity and emotional sensitivity to both external and internal stimuli which, in turn, might interfere with daily life. High SPS is seen in 20% of the populations studied (Aron and Aron, 1997); recently Lionetti et al. (2019) indicate around 30% of the people (Lionetti et al., 2018, 2019; Pluess et al., 2018). It seems equally distributed in both genders (Kagan and Kagan, 1994; Kristal, 2005). Importantly, SPS was identified as a one-dimensional construct, differing from introversion, emotionality, neuroticism, and shyness. SPS seems only related to high sensitivity (Aron and Aron, 1997).

The sensitivity trait represents the result of a careful strategy of processing environmental information, carried out before taking an action (Aron et al., 2012). This strategy can lead to two outcomes - more adaptive or less adaptive depending on the circumstances: increased awareness of environmental details or overstimulation resulting in anxiety or avoidance conduct (Aron, 2018). Research on this topic states that deeper processing (i.e., a more meaningful analysis of information) of stimuli would not be stimulus-specific but is the result of high responsivity to salient environmental stimuli (Aron et al., 2012). The evolutionary purpose of this kind of information processing is to utilize information obtained in situation A (where more details are noticed) to better predict the future and enact more effective responses in situation B (the same as situation A, where people practise the behaviors previously learned) (Aron et al., 2012; Aron, 2018).

It is important to underline that SPS is not to be considered a pathological clinical condition, however high sensitivity could expose to an increased risk of developing psychopathologies, especially during childhood and adolescence (Aron, 2018; Greven et al., 2019; Lionetti et al., 2022). In particular, High SPS children who have had an unhappy childhood or have been exposed to harmful environments would be more vulnerable to anxiety, depression, and high levels of perceived stress with physical issues such as pain or fainting (Liss et al., 2005; Benham, 2006). In contrast, children who had a happy childhood and grew up in a supportive environment would develop several adaptive advantages, even to a greater extent than non-sensitive children (Pluess and Belsky, 2013).

In such a case, it is possible to detect advantageous sensitivity, that is the propensity to disproportionately benefit from positive experiences and contexts (Pluess and Belsky, 2013, 2015). Conversely, individuals made vulnerable may have a greater propensity to succumb to the negative effects of adversity, as explained by the diathesis-stress model. The two evolutionary directions are not mutually exclusive (Belsky and Pluess, 2009; Bakermans-Kranenburg and van Ijzendoorn, 2011). In fact, the SPS would likely be a predictor of an increased likelihood of benefiting from positive contexts and situations although it exposes a person to greater potential vulnerability (Belsky, 2005; Pluess and Belsky, 2009).

A recent study explored the vantage sensitivity hypothesis to understand possible individual differences in response to psychotherapist treatment (de Villiers et al., 2018). According to the Authors, individual differences in response to environmental exposure can be explained by the diathesis–stress model, which conceives psychological vulnerability as due to the interaction between an individual’s inherent propensity for vulnerability, and some sort of external life stressor. Endogenous markers of vantage sensitivity appear to fall into genetics (5-HTTLPR); physiology (cortisol reactivity), and psychological traits (childhood negative emotionality) with several factors of vulnerability (Obradović et al., 2010; Ramchandani et al., 2010; Drury et al., 2012; Pluess and Belsky, 2015; Bozzatello et al., 2019, 2021; Longobardi et al., 2020; Morese and Longobardi, 2020). Several higher-order cognitive processes involve individual sensitivity markers and represent potential facilitators of vantage sensitivity (or environmental sensitivity more generally): attentional processes, reward sensitivity, social sensitivity, and stress reactivity (Drury et al., 2012).

Importantly, the concept of environmental sensitivity can encompass differential susceptibility, vantage sensitivity, biological sensitivity to context, and SPS at the same time (de Villiers et al., 2018). The centrality of the nervous system in that context can be evaluated in terms of “neurosensitivity,” which in turn would manifest itself physiologically and at the psychological level. In addition, the quantifiable SPS neurobiological trait influences the degree of sensory stimuli processing (de Villiers et al., 2018). Authors through the review of literature indicate interesting results about a growing number of studies that report that some people with heightened sensitivity benefit more from psychological intervention than others.

The implication of the above is particularly important: it means that environmental sensitivity factors explain individual differences in response to both adverse and supportive experiences, such as psychotherapy. Therefore, knowing individual sensitivity could help in the strategy and the design of clinical practice according to a tailored patient-centered approach.

The topic has been studied empirically, but the ability to predict clinical outcomes remains limited (Pluess and Boniwell, 2015; Nocentini et al., 2018). It has been reported, however, that targeting interventions can have a number of practical advantages, both financially and in terms of improving clinical services. Indeed, individuals with higher levels of sensitivity and responsiveness may require shorter interventions, while those with higher levels of resilience may require longer, more intense interventions or different strategies. According to de Villiers et al. (2018), this assumption can also be applied to educational and social welfare plans.

On the other side, SPS may expose highly sensitive people to an increased risk of psychopathology. Indeed, Individuals with SPS report, for example, increased frequency and distress of nightmares (Carr et al., 2021). SPS has been previously found in autism spectrum disorder (Joosten and Bundy, 2010), attention deficit hyperactivity disorder (Panagiotidi et al., 2020), mild cognitive impairment, and dementia (Rhodus et al., 2022).

In 2012, Aron published a meta-analysis in which she analyzed 4 typical features of HSP: inhibition of behavior, greater sensory awareness, deep information processing, and stronger and more emphasized emotional responses. These are summarized and conceptualized in the acronym DOES (Aron, 2018):

Considering the above, a reliable assessment approach to HSP is the use of standardized questionnaires such as:

In addition to the DOES (Aron, 2018), other typical characteristics of a highly sensitive individual are considered in these rating scales. Examples are conscientiousness, creativity, spirituality, and love of nature, but also, higher physical sensitivity, a more responsive immune system, and higher pain sensitivity (Table 1).

Sensory-processing sensitivity represents a trait that highlights interindividual differences in sensitivity to environments that can encompass a wide range of internal and external stimuli, either conditioned or unconditioned, as well as physical environments, sensory environments, social environments, and internal events (such as thoughts, feelings, and bodily sensations for example for hunger and pain) (Greven et al., 2019).

The anterior cingulate cortex (ACC), the anterior insula (AI), and the primary and secondary somatosensory cortex (S1 and S1) have been considered as hubs of physical pain (Eisenberger, 2012). More recently, neuroimaging and neurophysiological evidence reported that noxious stimuli activated neural correlates and connectivity in several cerebral areas: insular cortex, prefrontal cortex, somatosensory cortex, ACC, thalamus (Mercer Lindsay et al., 2021).

Research on the neural correlates of sensitivity to physical pain associates it with cortical thickening in S1, posterior cingulate cortex, and the orbitofrontal cortex (Hsiao et al., 2020). Nonetheless, (hyper)activation of some of these regions in pain-sensitive individuals than in pain-insensitive individuals has been also observed (Coghill et al., 2003; Erpelding et al., 2012).

The lingering effects of this pain sensitivity may exacerbate the effects of brain trophism resulting from chronic pain. Chronic pain causes both central and pathology-specific gray matter alterations in several cerebral networks (Cauda et al., 2014). Common alterations have been detected in the prefrontal regions, post and precentral gyri, thalamus, cingulate cortex, anterior insula, basal ganglia, periaqueductal gray, and inferior parietal lobule. As a highly salient stimulus, pain constantly taxes the salience and attentional processing systems, interfering with cognitive abilities and consuming emotional and cognitive resources. Most available studies report an overlapping contribution of salience and attention networks in subjects with various chronic pain conditions and pathologies (Cauda et al., 2014, Palermo, 2022).

Most of the cerebral responses are activated when physical pain is present, but they can also be elicited when pain is not triggered by a physical stimulus (Mouraux and Iannetti, 2018). For example, similar neural underpinnings can be observed in social pain (Eisenberger, 2012). While physical pain is related to actual or potential tissue damage, social pain is associated with psychological distance from other people or social groups (Xiao et al., 2020). Indeed, social pain is considered a strong experience of discomfort and distress caused by ostracism (i.e., social exclusion or loss such as rejection from the others or the own group) that involve affective, behavioral and cognitive iatrogenic consequences (Eisenberger and Lieberman, 2004; Eisenberger, 2012; Wesselmann et al., 2012; Sturgeon and Zautra, 2016; McIver et al., 2019; Kiefer et al., 2021; Schwarz et al., 2021; Jauch et al., 2022). Physical and social pain share not only physiological-adaptive characteristics to the environment, psychological and behavioral manifestation, but also a strong capacity for interaction and interpenetration (Xiao et al., 2020). Nevertheless, social pain neurobiology has been studied for much less time.

The “Cyberball Game,” a virtual task in which participants pass the ball with two virtual players, has been used in neuroimaging studies to understand the neurophysiological basis of social pain (or ostracism). At first, both players pass the ball normally, but after a while they begin passing it only to one another, excluding the real player (Hartgerink et al., 2015). The consequences of exclusion from the game evoke negative feelings of discomfort and unpleasantness and activate neural areas devoted to processing negative affect, and shared with neural substrates of physical pain: the dorsal ACC, the subgenual ACC, and the anterior insula (AI) (Coghill et al., 2003; Masten et al., 2009, 2011; Eisenberger, 2012; Erpelding et al., 2012; Cacioppo et al., 2013; Novembre et al., 2015; Rotge et al., 2015; Auriemma et al., 2020; Hsiao et al., 2020).

The possible overlap of physical pain with social pain leads us to hypothesize that highly sensitive individuals are hyper-reactive to both types of pain, but to date there is no evidence on the relationship between pain sensitivity and high HSP scores.

A recent study on ostracism was concerned with understanding how behavioral and neural correlates could be modulated by social support (Morese et al., 2019). The authors administered the Cyberball Game to their normal sample, as modified by Novembre et al. (2015). Through functional Magnetic Resonance Imaging (fMRI), participants were observed to activate their brains in response to receiving the emotional, appraisal, or no social support from a friend (Lo Gerfo et al., 2019; Morese et al., 2019). At the neural level, social-emotional support (hand caresses) reduced feelings of unpleasantness and reduced AI recruitment, a core brain area associated with negative emotional states both in social pain and in physical pain (Morese et al., 2019; Palermo, 2022). In contrast, social appraisal support (text messages) would not attenuate the effects, but on the contrary, would increase feelings of unpleasantness (Morese et al., 2019). On a neural level, the right temporal parietal junction (TPJ) is less activated (a component of the ToM network that detects inconsistencies and distinguishes oneself from others), resulting in a reduced need to comprehend the social situation (Lo Gerfo et al., 2019; Morese et al., 2019). In line with this finding, an increase in subACC activity (i.e., an increase in negative affectivity) was also observed (Morese et al., 2019).

Although there are no relevant studies on this yet, we can speculate, given the wide range of evidence (both neural and behavioral) in support, that a highly sensitive individual is hyper-reactive not only to physical pain but also to social pain. Consequently, social-emotional support and not just social appraisal support might prove to be an effective supplement to traditional psychotherapies.

In support of this hypothesis, a recent study conducted by Ren et al. (2020) suggested a possible relationship between pain sensitivity and empathy. Authors found that individuals with high pain sensitivity would experience higher empathy for other people’s pain, manifesting it through stronger emotional reactions. Importantly, a significant correlation between pain sensitivity and emotional empathy in the context of a mediation-moderation induced by anxiety, catastrophizing, and fear was found. Those behavioral findings are consistent with meta-analytic connectivity analysis on experimental pain (Palermo et al., 2015). A highly distributed perceptual set of self-regulation can prompt brain areas to elaborate information in which emotion, action, and perception represents an important role (Palermo et al., 2015). Highly sensitive metacognitive-executive functions (such as ToM and mentalizing) and the intensity of emotional reactions normally associated with highly pain-sensitive individuals can therefore be considered prototypical characteristics of HSPs. What has been described leads us to speculate that social pain resulting from the SPS trait may be significantly perceived as greater in HPSs.

Understanding how hypersensitivity, negative situations, and expectations influence nociception is important to understanding how nocebo responses are neuromodulated in HSPs. The implications that result are of great clinical-applicative importance since new approaches for the management of physical and social pain in these people are needed.

Nocebo hyperalgesia could represent the outcome of negative anticipations leading to extended pain experiences (Tracey, 2010). Acute psychological stress affects nocebo responses and, consequently, the pain threshold, through its action on serotonin, dopamine, and norepinephrine (Palermo, 2022). Because dopamine and norepinephrine specifically potentiate the ability to process and modulate pain, it is critical that these neurotransmitters are well-balanced (Palermo, 2022).

Highly sensitive people are more prone to stress (Gulla and Golonka, 2021). The reason could be attributed to genetic mutations found in HSPs in the three neurotransmitters directly related to stress and pain tolerance (Chen et al., 2011). In a stressed HSP, neurochemicals are dysregulated, deteriorating the nervous system’s ability to cope with both short-term and long-term pain (Chen et al., 2011).

Anxiety, stress, a sense of overload, and catastrophism impact on general well-being (Gulla and Golonka, 2021) and pain expectancy (Palermo et al., 2015) and trigger hyperalgesia phenomena (nocebo effects), easily verified in psychobiological responses associated with pain anticipation (Palermo et al., 2015; Amanzio and Palermo, 2019). Therefore, the psychological mechanisms of emotion management become fundamental. Indeed, modulatory cortical networks involved in placebo analgesia largely overlap with those involved in the regulation of emotional processes, while nociceptive brain networks are downregulated in parallel with behavioral analgesia (Amanzio et al., 2013).

According to Gulla and Golonka (2021), attention awareness can moderate the relationship between HSPs and resilience to psychophysical stress, including pain. Indeed, the positive relationship between sensing subtle emotions and tolerating negative emotions is strengthened by attentional awareness. That finding is in line with a conceptualization of executive-metacognitive functions as predictors of disease prognosis and treatment compliance (Morese et al., 2018).