Embodiment is defined as the sense of having a body, and the body can be considered to be both the subject and object of medical science and practice (Gallagher, 2001). One of the main goals in the field of cognitive neuroscience is to investigate how we experience ourselves inside a body as it interacts continuously with the environment. Historically, the bodily self has been described as “obvious and unproblematic” (James, 1890) and connected to a single somatic sensory system such as visceral interception (Damasio, 2000); however, more recently, embodiment has been described as being composed of several different structurally organized subjective components (Longo et al., 2008), as opposed to a single dimension. Hence, we feel our self as being inside a body, a body that moves according to our intentions (Kilteni et al., 2012a) and that interacts with the environment. Indeed, the sense of embodiment is thought to emerge from a complex interaction between bottom–up and top–down signals (Longo et al., 2008).

At first glance, experimental manipulation of embodiment might seem problematic; however, in the last few years, many studies have investigated bodily perception and revealed alternative ways of manipulating embodiment by using fake body parts. One example of this is the rubber hand illusion (RHI) study, in which synchronous visuotactile stimulation of both a rubber hand located within the visual field of the participant, and the participant’s real hand, located outside the visual field of the participant, confers an illusion of ownership over the rubber hand (Botvinick and Cohen, 1998). Since this study, many researchers have investigated how to manipulate body perception through the use of fake bodies such as a mannequins (Ehrsson and Petkova, 2008), mirrors (Ramachandran et al., 2009a), and virtual reality (VR) (Slater et al., 2008, 2010). Slater et al. (2008) were the first to replicate the RHI study in VR inducing ownership of a virtual hand based on visuo-tactile correlations, in an experience termed the “virtual hand illusion,” while a similar ownership was successfully induced by means of visuomotor correlations in Sanchez-Vives et al. (2010) (see Figure 1). A number of studies have focused on the use of body illusions to address pathological conditions such as chronic pain, with the focus being on the analgesic effects of cross-modal perception (e.g., pain and vision) (for reviews, see Boesch et al., 2015, 2016; Martini, 2016).

Chronic pain, where the symptoms last beyond normal tissue healing times, is the most burdensome health issue worldwide in terms of years lived with disability (Vos et al., 2012) and economic cost (Gaskin and Richard, 2012). In some cases, the negative emotional experience of pain can even lead to suicidal intention (Campbell et al., 2016). Current management strategies including physical activity/exercise and psychological interventions such as cognitive behavioral therapy show short-term effects only, with small effect sizes (Williams et al., 2012; Geneen et al., 2017), while pharmacological agents, such as opioids, have limited efficacy and carry significant risks and side effects (Hofmann et al., 2012; Carter et al., 2014). Indeed, the economic burden of prescription opioid misuse alone in the United States is estimated at $78.5 billion a year, including healthcare costs, lost productivity, addiction treatment, and criminal justice system involvement (Florence et al., 2016). Many investigators have therefore attempted to look for new ways to manage pain states via non-pharmacological means (Carter et al., 2014). This paper presents a review of experimental and clinical studies that have explored the manipulation of an embodied virtual body in immersive VR for both experimental and clinical pain relief.

The capability of our brain of having a representation of our body results in a mental construction composed of perceptions and ideas about the dynamic organization of our own body, involving vision, touch, proprioception, interoception, motor control, and vestibular sensations (Maselli and Slater, 2013). In this regard, embodiment is defined as the sense of having a body. But to what are we referring when we talk about having a body? Longo et al. (2008) described it as follows:

These different descriptions of embodiment refer to the fact that we are able to feel the sense of having a body by integrating the different sensory signals arriving to our body, which our brain interprets to create a coherent representation of our self. In this regard, Longo et al. (2008) discuss the fact that others have described embodiment as the “storm-center of experience” arriving to our body, resulting in an essential factor for the construction of our internal life (James, 1905), and that other authors support the idea that embodiment is key for the construction of our inner self representation by demonstrating that the sense of embodiment is also closely related to the sense of self, and is strongly related to our individual psychological identity (Edelman, 2005; Cassam, 2012).

However, some investigations have shown that embodiment is divided into different subcomponents that form our body representation, such as body image and body schema (Gallagher and Cole, 1995). In this regard, it is known that body image and body schema play a fundamental, but clearly differentiated, role in understanding the sense of self and in individual psychological identity.

Gallagher (2001) has described body image as “an intentional content of consciousness that consists of a system of perceptions, attitudes, and beliefs pertaining from one’s own body.” In contrast, body schema has been described as an “automatic system of processes that constantly regulates posture and movement” and is mostly controlled by the sensorimotor system (Gallagher, 2001). One clear example of the difference between body image and body schema is the difference between perception of movement (conscious awareness of movement), related to body image, and the final execution of that movement (motor performance), related to body schema.

Studies aimed at analyzing body image have distinguished three different intentional elements: (1) the subject’s perceptual experience of his/her own body, (2) the subject’s conceptual understanding of the body, and (3) the subject’s emotional attitude toward his/her own body (Cash and Brown, 1987; Powers et al., 1987; Gardner and Moncrieff, 1988). The body image relies in the congruent inputs for all sensory and motor systems, and it has been described that experimental asynchronous multisensory stimulation results in distortion of body image (Perez-Marcos et al., 2018). In contrast, body schema is not the result of mental perception, beliefs, or attitudes, involving instead a system of motor functions or programs that operate “below” the level of self-referential intentionality, playing a dynamic role in governing posture and movement in a close automatic/subconscious way (Gallagher, 2001). While subconscious and automatic, body schema is not just a matter of mere reflex. Actions controlled by the body schema can be precisely shaped by the intentional experience or goal-directed behavior of one’s own body (Gallagher, 2001). Therefore, once one becomes aware of perceptual limb position, movement, posture, pleasure, pain, and kinesthetic experience, such awareness contributes to the perceptual aspect of one’s body image and such awareness may interact with one’s body schema (Gallagher, 2001).

According to Melzack (1990), the body schema is controlled by a distributed neural network, or neuromatrix, mostly prewired by genetics, but flexible and open to the continuous shaping influence of experience. This network includes the somatosensory system, reticular afferents to the limbic system, and cortical regions that are important for self-recognition and recognition of external objects and entities. Somatosensory inputs to the brain from different modalities are essential for bodily awareness, especially those from proprioceptors, as demonstrated by Lackner (1988), in which he showed changes in body awareness using muscle vibration and other somatic manipulations. The sense of vision is also very important, as demonstrated by the evident anatomical distortions when congenitally blind subjects attempt to draw their own and other people’s bodies (Critchley, 1979). Further, visual information regarding the hand’s position is normally in accordance with the proprioceptive information regarding its position (van Beers et al., 1999). Tactile events regarding the body are strongly coupled with visual information (if available) of the same event (Pavani et al., 1999). Similarly, execution of movements is normally corroborated by congruent visual and tactile feedback (Janczyk et al., 2009).

How the brain represents our body is a fundamental question in cognitive neuroscience (Slater and Sanchez-Vives, 2016). How can we tell that our hand is part of our body and a physical object like a book is not? We generally believe that our own internal body representation is stable; however, some investigations have elicited the illusion of body ownership over objects that are not part of the body at all, which suggests that our body representation is actually highly malleable. In addition, out-of-body illusion research was reignited by Botvinick and Cohen (1998) with their RHI study. In the RHI study, perceived ownership of the rubber hand occurs because the brain’s perceptual system resolves the sensory conflict between the congruent visuotactile information (the visual position of the rubber hand together with the tactile stimulus from the stroking) and the proprioceptive input (which indicates the position of the real hand) by prioritizing the importance of the visuotactile input over the proprioceptive input, integrating the two separate but synchronous inputs (visual and tactile) into a single prediction, as a result of which participants have the perceptual illusion that the rubber hand is their real hand. The visuotactile input is sufficient to override any contradicting proprioceptive input and produce the (incorrect) prediction that the real hand is located closer to where the rubber hand is, a phenomenon known as “proprioceptive drift.” Interestingly, if the visual and tactile stimulation are asynchronous, the illusion does not occur, suggesting that congruous multisensory input is required to produce the illusion. Later, Armel and Ramachandran (2003) demonstrated than when the rubber hand is threatened, there is a strong skin conductance response (SCR), indicating a physiological response to the threat. In this study, they argue that our body representation is continuously updated based on the stimuli being received. With synchronous multisensory perception, we can feel that a rubber hand is our real hand because the brain quickly generates the corresponding illusion as a way of resolving the contradiction between the visuotactile and the proprioceptive inputs (Slater and Sanchez-Vives, 2016).

Further, it has been shown that BOI may also be induced over the entire body in healthy subjects by using a mannequin (Petkova et al., 2011). In this study, healthy subjects observed an artificial body (a mannequin) through a head-mounted display connected to a two-synchronized-color video cameras oriented down at the mannequin body. As in the RHI study and in order to induce a BOI, participants received synchronous visuotactile stimulation at the same place in both the artificial and the real body. This whole body illusion is commonly known as the full BOI (Slater et al., 2010; Maselli and Slater, 2013). The full body ownership illusion from a first-person perspective is described as the feeling of owning an artificial body, which substitutes the real body as the origin of perceptual sensations. In this regard, some investigations have demonstrated that in order to induce a BOI, first-person visual perspective of the artificial body part or full body is key (Ehrsson and Petkova, 2008; Slater et al., 2010; Petkova et al., 2011). In addition to visuotactile stimulation and visual perspective, it has been shown that subjects may also experience the illusion when visuotactile stimulation is substituted by other modalities of multisensory and/or sensorimotor stimulation, such as sensorimotor contingencies in active or passive movements (Tsakiris et al., 2006; Sanchez-Vives et al., 2010; Kalckert and Ehrsson, 2012).

Hence, in the context of full-body illusions, self-location can be advantageously regarded as the combination of two parallel spatial representations: (1) an abstract allocentric representation of the body, mainly associated with visual perspective (first-or third-person visual perspective), and (2) an egocentric mapping of somatosensory sensations (visuotactile or visuomotor sensations) into the external space, mainly associated with peripersonal space. As reported by specific experimental paradigms adopted to induce out-of-body illusions, if these spatial representations are selectively or simultaneously altered, this could have implications for the sense of ownership of an artificial body (Maselli, 2015).

Nowadays, the integration of technology in the field of applied neuroscience such as VR systems allows the replacement of a person’s real body with a virtual body representation, allowing the subject to feel embodied in a virtual body. In this regard, several investigations demonstrate that one may experience the sense of ownership over a virtual limb (Slater et al., 2008) and even an entire virtual body (Slater et al., 2010) by using immersive VR. In the latter study, Slater and colleagues demonstrated a full-body transfer illusion in which male subjects were able to embody a virtual female body. This finding was demonstrated subjectively (by questionnaire) and physiologically (through heart-rate changes) in response to an attack on the virtual body.

In addition, VR has been defined as a way to simulate reality and real-life situations (Slater and Sanchez-Vives, 2016). For example, it has been demonstrated that when a virtual knife stabs an embodied virtual body in an immersive VR environment, participants demonstrate an autonomic response and motor cortex activation in preparation to move the hand out of the way, just as they would in real life (González-Franco et al., 2014). Hence, anything that can happen in reality can be programed to happen in VR and be experienced as a real situation (Slater and Sanchez-Vives, 2016).

VR allows the experimenter to manipulate not only the virtual environment but also the embodied virtual body in ways that would be impossible in physical reality (Bohil et al., 2011). For example, immersive VR allows the manipulation of body representation in terms of structure, shape, size, and color, in ways that can contrast sharply with our own body image (Kilteni et al., 2012a, b; Banakou et al., 2013; Peck et al., 2013). Further, it has been shown that manipulating the characteristics of the virtual body may influence the physiological responses of the real body (Martini et al., 2013; Bergström et al., 2016), and may also modulate behavioral responses of the subjects (Osimo et al., 2015; Seinfeld et al., 2018). For this reason, immersive VR has been shown to have many potential applications in the fields of psychotherapy, rehabilitation, and behavioral neuroscience (for reviews, see Tarr and Warren, 2002; Martini, 2016; Riva et al., 2018), and even consciousness studies (for a review, see Sanchez-Vives and Slater, 2005).

At the beginning of the 21st century, VR was introduced to the field of pain management (Hoffman et al., 2000a). The first application of VR in clinical pain was a video game in which adolescent and adult burnt patients experienced less pain while they were playing (Hoffman et al., 2000b). Later, Hoffman and colleagues conducted an fMRI brain scan study in which they found that VR greatly and significantly reduced pain in five brain regions of interest related to pain (the anterior cingulate cortex, primary and secondary somatosensory cortex, insula, and thalamus) in healthy subjects exposed to thermal stimulation (Hoffman et al., 2004). Some years later, a second fMRI study demonstrated that the pain reduction experienced by using VR was comparable to the analgesic effect of a moderate dose of hydromorphone pain medication (Hoffman et al., 2007). Up to this point, the analgesic properties of VR had been mostly attributed to its powerful distractive capacity. However, its effectiveness has been demonstrated in the management of mild and severe pain states (Doctor et al., 2002; Hoffman et al., 2011, 2014). In addition, the positive pain-relieving effects of VR may also be mediated through a reduction in anxiety and through the user experiencing positive emotions such as a sense of fun (Triberti et al., 2014).

One reason in favor of the distractive effect on pain associated to VR in the studies from Hoffman and colleagues is because of the lack of embodiment in a virtual body in the VR scenarios of their studies, in which patients were observing fun and distractive situations in a display instead of being embodied in a virtual environment through an immersive VR system. In addition, Malloy and Milling, in a review on the effectiveness of VR intervention for pain relief, reported that immersive VR is more effective in promoting analgesia than non-immersive VR systems (Malloy and Milling, 2010). The difference between these two systems is the lack of embodiment in the non-immersive VR systems, whereas using immersive VR systems, one may be embodied in a virtual body and immersed in the virtual world, feeling present in the generated VR scenario (Sanchez-Vives and Slater, 2005). It has been reported that this “transportation of consciousness to another place” involved in the sense of presence in a virtual environment might be strong enough to diminish sensations of pain (Sanchez-Vives and Slater, 2005). Hence, although Hoffman and colleagues used an immersive VR system in their pain studies, these early pain studies using VR did not include embodiment in a virtual body.

The sense of being present in an immersive VR scenario while being embodied in a virtual body offers the possibility of modulating pain perception by observing the embodied virtual body from a first-person perspective (for a review, see Martini, 2016). The representation of the body is modulated by the integration of different sensory signals, and this has been extensively investigated (Macaluso and Maravita, 2010; Medina and Coslett, 2010; Serino and Haggard, 2010; Wesslein et al., 2014). In this regard, in IVR, we can therefore act on the virtual body seen from a first-person perspective and experimentally manipulate the multisensory integration in a highly controlled way.

This review has discussed the potentialities of using an embodied virtual body in immersive VR for pain modulation. Specifically, we have discussed the use of multisensory integration applications, by means of body ownership illusions, to decrease pain perception in healthy and clinical populations.

In a systematic review conducted by Boesch et al. (2016) of non-virtual body illusions (illusory changes of size, mirror therapy, etc.) on clinical pain, they found that there is limited evidence to suggest that bodily illusions can alter pain, but some illusions, namely, mirror therapy, bodily resizing, and use of functional prostheses, show therapeutic promise. Concerning the effects of embodiment on clinical pain, the authors discuss two studies of patients with chronic pain that showed no effect of embodiment on pain levels and suggest that a potential explanation is that embodiment and pain modulation may be separate processes. However, the review did not examine any studies that used immersive VR studies to induce embodiment. Here, we show that through an embodied virtual body, we may modulate body representation and change pain perception in healthy and clinical populations.

Regarding the importance of body representation in pain perception, it is known that many chronic pain patients have a distorted representation of the affected part of the body (Lewis et al., 2007; Moseley, 2008; Senkowski and Heinz, 2016). Further, misrepresentations of the body have been associated with pain (Lotze and Moseley, 2007), and several reports support structural and functional differences between people with and without pain, both at a cortical or at a subcortical level, in brain areas involved in body awareness and body perception (Flor et al., 1997; Pleger et al., 2006; Gwilym et al., 2010). Distortions of body perception involving a painful part of the body (i.e., the body part feeling larger than it really is) have also been demonstrated (Moyer, 2005; Lewis et al., 2007). There is some evidence that treatment directed at changing these functional brain alterations, such as graded motor imagery and sensorimotor retraining (Moseley, 2004, 2006; Pleger et al., 2006), reduces pain, which suggests that there is a bidirectional link between pain and body perception. In addition to this, it has been shown that pain perception is reduced with a corresponding restoration of functional cortical representation of the painful part of the body in CRPS patients (Pleger et al., 2006).

These studies support a link between body perception and clinical disorders such as pain, highlighting the advantages of using embodiment through VR systems in neurorehabilitation and pain management. Nonetheless, robust and suitably powered randomized control trials are needed to further explore the full potential of body illusions and embodied technologies to modulate pain perception, especially with the use of immersive VR. Furthermore, further investigations aimed at modulating pain perception through an embodied virtual body with larger sample sizes will allow a better understanding of the contribution that the subjective feeling of ownership over an embodied virtual body has on pain perception. Moreover, future studies on this topic may make use of brain imaging techniques, which will allow better identification of the neural structures underlying the complex link between modification of body perception and pain.

Interestingly, virtual body embodiment may also allow the study empathy in pain. It is known that the mere observation of other people in pain tends to elicit empathic responses regarding pain perception in one’s body (Lamm et al., 2011; Benuzzi et al., 2018). Hence, what will happen if we use embodiment to create a pain-free representation of the body? Although some authors have started to investigate how to use empathy for pain relief by using embodiment (Fusaro et al., 2016), further investigations are needed to create new behavioral and cognitive training methods for modulating pain perception in clinical populations.

The studies commented throughout this narrative review, especially those conducted with chronic pain patients, pave the way for the design of new rehabilitation protocols with prolonged and repeated doses of embodied virtual body in immersive VR to tackle chronic pain disorders, and enable the integration of such “digital therapy” with existing conventional pain treatments.

MM-G contributed to the bibliographic review and writing of the manuscript. TD contributed to the writing and review of the manuscript. SB and GS contributed to the bibliographic suggestions and review of the manuscript. MS-V and CT contributed to the supervision of the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.