Chronic neuropathic pain (CNP) can derive from lesions and diseases involving the somatosensory nervous system [1]. This type of pain is usually chronic, that is, it either persists continuously or manifests with recurrent painful episodes, resulting from etiologically diverse disorders affecting the peripheral or the central nervous system [2,3]. In this context, CNP can be a common manifestation of various neurological diseases (eg, complex regional pain syndrome [CRPS], phantom limb pain [PLP], and spinal cord injury [SCI]), as patients may experience altered sensory processing and disruptions in body representation (BR) [4,5]. These pain experiences are frequently linked to the dysregulation of nociceptive pathways, including the spinothalamic, spinoreticular, and spinomesencephalic tracts, which contributes to increased pain sensitivity and persistent discomfort [4]. To better quantify these complex pain experiences, assessment tools such as the visual analog scale, McGill Pain Scale, and Numerical Rating Scale provide valuable information about the intensity and characteristics of pain (such as quality, location, and exacerbating and ameliorating factors), highlighting the complex and often severe impact on a patient’s quality of life [6]. A growing body of research supports the critical role of BR in pain perception for patients with neurological conditions [7-13]. BR refers to the cognitive and sensory mapping of the physical self, a process that is often distorted in neurological conditions [10]. This distortion can contribute to an intensified experience of pain, highlighting the need for therapeutic approaches that address this cognitive-sensory mismatch [14,15]. A clearer understanding of this connection emerges when considering that disruptions in the somatosensory and motor cortices can lead to a fragmented BR, where sensory inputs are misinterpreted, resulting in exaggerated or worsened pain symptoms [16-18]. This effect is associated with maladaptive neuroplasticity in cortical areas such as the primary somatosensory cortex, anterior cingulate cortex, and insular cortex, which together shape pain perception and intensity [10,14]. Building on this understanding, significant advancements in pain research have emerged from the introduction of the neuromatrix theory proposed by Melzack [19]. This model views pain as a complex experience shaped by sensory, emotional, and cognitive inputs within a biopsychosocial framework [19]. Within this framework, the neuromatrix, a broad neural network, processes pain by integrating physiological and psychological signals [19,20]. However, recent research has suggested that pain intensity can be dissociated from responses in the neuromatrix, emphasizing the importance of nonnociceptive factors such as emotions and anticipatory anxiety [21,22]. This perspective underscores that pain, particularly in its chronic neuropathic forms, is not merely a physiological reaction to tissue damage. On the contrary, it reflects a multifactorial experience shaped by the complex interaction of sensory, emotional, cognitive, and social dimensions. This multidimensional nature is evident in the phenomenon of distorted BR, which can amplify pain perception through maladaptive sensory processing and disrupted cognitive integration [10,13]. This disruption of BR often interacts with psychological constructs (ie, catastrophizing, anticipatory fear, and emotional distress), which can further intensify the pain experience, exacerbating symptoms beyond the initial nociceptive input [5,23]. In addition to these individual factors, cultural and social contexts influence how individuals interpret and express pain, further demonstrating its biopsychosocial complexity. This comprehensive approach is crucial for developing effective therapeutic strategies, as highlighted by the growing application of virtual reality (VR) to recalibrate BR and modulate pain perception through immersive and tailored interventions [19,24]. Indeed, psychological factors such as attention and cognitive interpretation are crucial in shaping pain perception; for instance, focusing on the painful stimulus tends to amplify pain perception, while distraction techniques can significantly reduce it [23,24]. In this context, interventions delivered through innovative technologies have proven effective in shifting attention away from pain, offering immersive environments that engage patients and diminish their perceived pain levels [25]. VR has emerged as a promising tool to fully immerse patients in simulated environments, using devices such as headsets and noise-canceling headphones to create interactive experiences [26]. This technology has proven effective for pain management, particularly in chronic pain scenarios, helping patients redirect their attention and alleviate perceived pain [27]. Indeed, VR offers a promising avenue to address these challenges in neurological rehabilitation [21,28]. By providing immersive and controlled environments tailored to individual sensory needs, VR interventions can stimulate motor and sensory processing to recalibrate BR [29]. This recalibration or “remapping” of the BR has shown the potential to modulate pain by altering nociceptive processing and sensory integration [24,30]. This effect provides the basis for understanding how VR can be leveraged in pain management. In fact, VR may have a positive impact on pain by modulating sensory experiences and perceptions, shifting attention, and recalibrating the internal body model [31]. Such “remapping” could play a crucial role in reducing pain intensity and improving functional outcomes in patients with neurological conditions. By facilitating the reorganization of BR, VR-based interventions help modulate pain perception through targeted alterations in sensory processing, offering new hope for managing CNP [31]. Moreover, research has shown that VR, combined with other psychological approaches such as relaxation and hypnosis, can optimize pain management, offering a noninvasive solution that integrates both physical and psychological aspects of the pain experience [24,26,27]. These distraction-based interventions have been especially effective for managing acute pain during medical procedures but also show potential for long-term treatment strategies [25]. This perspective underscores the need for an integrated approach to pain management.

Despite the promising potential of VR interventions in pain management, there is a lack of comprehensive evidence regarding their underlying mechanisms and long-term effectiveness in treating CNP in patients with neurological conditions. Specifically, the contribution of body remapping processes to pain modulation and functional recovery remains poorly investigated, particularly in relation to neurological conditions such as CRPS, PLP, and SCI. Thus, this systematic review aims to synthesize the existing evidence on the use of VR-based interventions for managing CNP in patients with neurological conditions. It focuses on exploring how VR can influence pain perception through mechanisms such as body remapping and improvements in BR, ultimately contributing to pain modulation and functional recovery. Furthermore, this review seeks to identify gaps in current research regarding the underlying mechanisms and long-term efficacy of VR interventions, while offering recommendations for future research directions and clinical applications.

Two reviewers (MGM and AC) conducted searches independently using Boolean operators and controlled vocabulary such as MeSH terms to ensure comprehensive and accurate identification of relevant studies.

The risk of bias in RCTs was assessed using the revised Cochrane Risk of Bias Tool for Randomized Trials (RoB 2) [33], while the Cochrane Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool [34] was used for the nonrandomized studies included in this review. In addition, the overall quality of evidence for each outcome was evaluated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) framework [35], which considers factors such as risk of bias, inconsistency, indirectness, imprecision, and publication bias to provide a comprehensive evaluation of the strength of evidence.

The 2 reviewers (MGM and AC) independently screened titles, abstracts, and full texts of all articles. Any discrepancies during this process were resolved by consulting a third reviewer (M Bonanno), who made the final decision. Extracted data included information on study design, the number of participants, participant characteristics, neurological disorders and pain types, details of the VR rehabilitation intervention (eg, duration and type), outcomes evaluated, and key findings. To minimize bias (eg, missing results bias, publication bias, time lag bias, and language bias), the reviewers conducted cross-validation of the extracted data.

Agreement between the 2 reviewers (MGM and AC) was assessed using the κ statistic, with a score indicating substantial agreement (>0.61) demonstrating the reliability of the screening and data extraction process. All articles meeting the inclusion criteria were thoroughly reviewed and summarized, with key topics identified based on predefined inclusion and exclusion criteria.

To synthesize the available data, a qualitative analytical approach was applied due to the substantial heterogeneity among the included studies. This heterogeneity was evident in various aspects, including the study designs, such as RCTs and observational studies; the VR intervention protocols, including immersive VR, visual feedback, and biofeedback; and the outcome measures used, such as pain reduction, changes in BR, functional improvements, and quality of life.

Given this methodological diversity, it was not feasible to conduct a meta-analysis, which requires a sufficient level of similarity across studies in terms of design, intervention type, and measured outcomes to ensure meaningful statistical comparison. To address this limitation and ensure methodological rigor, the synthesis was structured according to the synthesis without meta-analysis framework [36]. This approach promotes transparency and consistency in data interpretation, particularly when quantitative synthesis is not possible.

The qualitative synthesis aimed to identify key themes, recurring patterns, and discrepancies across the studies, focusing on outcomes related to pain reduction, the recalibration of BR, and improvements in functional outcomes and quality of life. Studies were categorized based on the type of VR intervention, patient characteristics, and the specific outcome domains addressed in the research.

The results were systematically presented in tabular form, summarizing key study characteristics, intervention details, and measured outcomes. This structured synthesis provided a comprehensive understanding of the potential effectiveness of VR-based interventions in managing CNP in patients with neurological conditions. In addition, the findings were critically evaluated to highlight existing gaps in the literature, address methodological limitations, and suggest specific directions for future research.

We identified 3984 articles, of which 396 (9.94%) were excluded after screening because they were duplicates, 22 (0.55%) were excluded because they were not published in English, and 3135 (78.69%) were excluded based on title and abstract screening. Finally, of the remaining 431 articles, 421 (97.7%) were removed based on screening for inadequate and untraceable study designs (refer to the PRISMA flow diagram [37] in Figure 1), and 10 (2.3%) articles that met the inclusion criteria were included in the review. These studies are summarized in Tables 2 and 3.

We assessed the risk of bias using appropriate tools based on the design of the included studies [7-9,11,12,38-42].

This review represents the first comprehensive analysis of the use of VR as a tool for body remapping in patients with neurological conditions, offering new insights into its potential to manage CNP. Existing studies demonstrate how VR leverages multisensory integration, including visual, tactile, and proprioceptive inputs, to enhance BR and reduce pain [43-45]; for instance, VR-induced leg illusions in individuals with SCI [46] and the manipulation of visual representations of the affected limbs in patients with CRPS reveal how sensory reconfiguration can alleviate pain and reshape BR [47,48]. These findings highlight VR’s capacity to disrupt maladaptive neural pathways and provide a drug-free alternative for pain management [49,50]. Combining VR with SCS enhances pain relief in SCI, while in CRPS, VR with biometric indicators such as heart rate variability reduces pain and modulates responses [45,51-54]. In PLP, kinesthetic inputs outperform sensory cues for rehabilitation [51,55]. Advances in PPS rehabilitation emphasize motor input and sensory awareness for recovery [56]. These findings highlight the role of VR as a transformative tool for neurorehabilitation [46].

Table 5 provides a comprehensive overview of the clinical applications of VR, detailing its benefits across neurological conditions and highlighting its capacity to integrate technology with therapeutic outcomes.

As stated previously, chronic pain involves maladaptive neuroplasticity, altered sensory pathways, and disrupted sensorimotor integration [57]. VR demonstrates significant potential in addressing these mechanisms by recalibrating distorted BR and promoting neuroplasticity [58]. VR reshapes the brain’s BR, reducing pain and improving functionality through integrating visual, tactile, and proprioceptive feedback within immersive environments [59,60]. This approach has been particularly effective in conditions such as CRPS, where VR reduces pain and associated disabilities by correcting altered BR [52,61].

For PLP, VR simulations of the missing limb have shown remarkable success in facilitating cortical reorganization and fostering sensorimotor synchrony, significantly alleviating pain [49]. VR also enhances PPS, aiding sensory and motor recovery in individuals with SCI and amputations [45,62]. VR enables highly personalized treatments that sustain neuroplasticity and enhance long-term therapeutic outcomes, incorporating biofeedback systems such as heart rate variability and spinal cord activity [54,63].

Beyond its physical benefits, VR addresses the emotional and cognitive dimensions of pain by engaging brain regions such as the insular cortex and anterior cingulate cortex [64]. For these reasons, immersive environments could promote the reduction of pain perception, improve emotional regulation, and foster attentional control, actively involving patients in their recovery process [65]. Furthermore, by creating personalized, adaptive interventions informed by real-time physiological data, VR refines its therapeutic effects, offering a robust platform for managing complex pain conditions [54]. These features underscore VR’s capacity to integrate multidimensional pain management strategies, paving the way for its expanded use in clinical practice.

Despite the promising potential of VR, several practical challenges must be addressed to ensure its effective integration into clinical practice. A significant obstacle is the individual variability in patient response to VR therapy. Factors such as age, cognitive capacity, technological familiarity, and psychological characteristics can influence patient engagement and therapeutic outcomes, potentially affecting the overall effectiveness of the intervention.

Another challenge is cybersickness, which can cause symptoms such as nausea, headache, dizziness, and disorientation, particularly in sensitive and predisposed individuals or during prolonged VR sessions. This side effect can reduce patient adherence and must be mitigated through appropriate system calibration and careful control of session duration.

Moreover, accessibility remains a major concern, especially in resource-limited settings. The high costs associated with hardware, software development, and technical support can prevent the widespread adoption of VR-based interventions. To address these barriers, future developments should focus on creating cost-effective VR solutions, including affordable headsets, mobile-based apps, and open-source platforms that reduce financial barriers for health care providers. Investments in infrastructure and simplified device usability through intuitive interfaces are also essential to ensure equitable access [66].

The requirement for specialized clinical expertise further complicates VR integration. Medical staff must undergo specific training to ensure the proper use of VR systems, maximize therapeutic benefits, and safeguard patient safety. Developing comprehensive training programs for clinicians will be vital to facilitate the widespread adoption of VR-based interventions while minimizing reliance on specialized technical support. Addressing these challenges will require ongoing collaboration among clinicians, researchers, and technology developers to refine VR systems; minimize adverse effects; and ensure that VR remains a practical, accessible, and effective tool for diverse patient populations.

The future of VR in pain management lies in expanding its applications to underexplored conditions and integrating cutting-edge technologies such as real-time neurophysiological monitoring, artificial intelligence (AI), and machine learning. AI is increasingly being applied in the field of rehabilitation, from assessment to treatment. Regarding rehabilitation treatment, AI-based applications can be implemented in the context of the metaverse—a virtual space in which users can interact with a computer-generated environment and other users [67]. In this context, AI applications can be used for motor assessment and for generating virtual character movements to enhance user engagement and enjoyment. These advances could enable the development of more precise and personalized interventions while providing deeper insights into pain mechanisms through adaptive and patient-specific feedback systems.

Moreover, due to its characteristics, VR can easily be combined with other targeted treatments, such as manual therapy, to alleviate chronic pain conditions.

Future studies should investigate the integration of VR with manual therapy because it may enhance chronic pain management through the modulation of pain perception, improving patient engagement and facilitating movement retraining in a controlled environment. However, successful implementation requires therapist expertise, patient suitability, and a strong therapeutic relationship to maximize benefits safely [68]. Furthermore, future research should prioritize large-scale longitudinal clinical trials to assess the long-term efficacy of VR interventions and establish standardized protocols that can be applied across different patient populations. In addition, identifying specific subgroups of patients more likely to benefit from VR therapy could enable more personalized and targeted treatment approaches.

By leveraging advances in immersive technologies and fostering interdisciplinary collaboration, VR could improve therapeutic and diagnostic strategies for different chronic pain conditions, including CNP. If financial, logistical, and clinical barriers are adequately addressed, VR has the potential to become a widely accessible, affordable, and evidence-based tool for pain management across various health care settings.

This review presents a comprehensive and qualitative synthesis of current evidence on the use of VR in pain management. It highlights the potential of VR-based interventions to recalibrate BR, alleviate pain, and foster neuroplastic changes. The strengths of this review lie in its analysis of diverse applications of VR across conditions such as CRPS, PLP, and SCI, providing insights into VR’s therapeutic possibilities. In addition, the inclusion of biofeedback and adaptive technologies reflects the growing emphasis on personalized treatment approaches.

However, several limitations must be acknowledged. This review is based solely on a qualitative analysis, which, while providing valuable descriptive insights, does not allow for a statistical evaluation of effect sizes or direct comparisons between studies. As a result, our review provides a comprehensive qualitative synthesis of the available evidence, offering valuable insights into the field of VR applications for specific chronic pain conditions, identifying key implications for clinical practice and considerations for future investigation.

Moreover, the GRADE assessment revealed variations in the quality of evidence across the included studies. The strongest evidence was found for the outcome of pain reduction, with most of the studies (7/10, 70%) providing moderate-quality evidence, despite some concerns regarding risk of bias and imprecision. The evidence supporting improvements in BR and functional outcomes was generally of moderate to low quality, primarily due to the heterogeneity of intervention protocols and patient populations. The weakest evidence was found for adherence to VR therapy because most of the studies (6/10, 60%) were observational and had a high risk of bias and inconsistency. These findings highlight the need for future high-quality, standardized RCTs with larger sample sizes to confirm the long-term benefits of VR interventions for CNP management. Indeed, many of the included studies were conducted with small sample sizes and heterogeneous methodologies, limiting the generalizability of the findings. Furthermore, the lack of standardized VR protocols complicates the comparison of results across studies. Future research should prioritize longitudinal clinical trials to assess whether the benefits of VR are sustained over extended periods. Given the persistent nature of chronic pain, it is essential to determine whether VR-induced relief remains effective over months or years, thus providing stronger evidence for its integration into long-term pain management strategies. Indeed, the lack of large-scale, standardized clinical trials limits definitive conclusions about the widespread applicability of VR-based interventions. Moreover, potential placebo effects and uncontrolled variables are a challenge in evaluating the true efficacy of VR-based interventions. Accessibility remains an issue because high technological demands and training requirements could hinder widespread implementation, particularly in low-resource settings.

Finally, another limitation of this review is the exclusion of studies focusing on migraines. While this decision was made to maintain a clear methodological focus on conditions where BR mechanisms are central, it might limit the applicability of the findings to other neurological conditions with different pathophysiological mechanisms. Future research could explore the role of VR in migraine treatment to expand the understanding of its broader applicability in neurological care.

In conclusion, this review highlights VR’s transformative potential in managing CNP. VR could offer a noninvasive, personalized therapeutic approach that recalibrates BR and promotes neuroplasticity by integrating sensory, emotional, and cognitive dimensions. Although challenges such as accessibility and methodological limitations remain, VR could represent a revolutionary tool in pain management in the neurological field.