Background: Chronic neuropathic pain is a common consequence of neurological conditions, such as spinal cord injury (SCI), complex regional pain syndrome (CRPS), and phantom limb pain (PLP). These conditions are often associated with distorted body representation (BR) and altered sensory processing. Virtual Reality (VR) offers immersive, multisensory experiences that can modulate attention, recalibrate BR, and potentially alleviating pain.

Objective: This systematic review aims to synthesize the existing evidence on the use of VR-based interventions for managing chronic neuropathic pain in neurological patients. It focuses on exploring how VR can influence pain perception through body re-mapping. Furthermore, this review seeks to identify gaps in current research, offering recommendations for future research directions and clinical applications.

Methods: We included original research studies that examined VR interventions in neurological patients with chronic neuropathic pain, assessing outcomes related to pain reduction, improvements in body representation, or functional recovery. Exclusion criteria comprised reviews, studies on animal models, migraine-related studies, and those lacking a clear VR intervention or relevant clinical outcome data. A comprehensive literature search was performed in PubMed, Web of Science, and Scopus for studies published between January 2014 and December 2024. The methodological quality of the included studies was evaluated using the Cochrane RoB2 tool for randomized controlled trials and the ROBINS-I tool for non-randomized studies. Given the heterogeneity in study design, VR protocols, and outcome measures, a qualitative synthesis approach was adopted based on the SWiM (Synthesis Without Meta-analysis) framework.

Results: Ten studies met the inclusion criteria, comprising both randomized controlled trials and uncontrolled experimental designs. These studies focused on the application of VR in SCI (n=4), CRPS (n=4), and PLP (n=2), utilizing interventions such as immersive VR, mirror visual feedback, visuo-tactile stimulation, and virtual body illusions. Sample sizes ranged from 9 to 70 participants, with varying degrees of neurological impairment. Most studies reported significant reductions in pain intensity and improvements in embodiment and perceived body ownership. In SCI, combining VR with neuromodulation techniques enhanced analgesic effects. In CRPS, modifying the visual appearance of the affected limb improved body image and decreased pain perception. In PLP, kinaesthetic and visual feedback delivered through VR environments significantly reduced phantom limb pain and improved movement representation.

Conclusions: Overall, the quality of evidence ranged from moderate to low, mainly due to small sample sizes, protocol heterogeneity, and risk of bias. Evidence regarding adherence to VR therapy was particularly limited. Nonetheless, VR shows strong potential as a non-invasive, patient-tailored therapeutic tool for chronic neuropathic pain. VR could provide innovative and engaging strategies to reduce pain and enhance functional outcomes in neurological populations. Future research should focus on developing standardized protocols and conducting large-scale, high-quality trials to validate its long-term efficacy and integration into routine clinical practice. Background: This review has been registered on Prospero with the following number: CRD42024606150.