Efficacy and Mechanisms of Virtual Reality Treatment of Phantom Leg Pain

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Project Summary Limb loss due to amputation is a common problem, occurring in nearly 2 million people in the US. Approximately 90% of individuals with limb amputation experience the persistent sensation of the missing extremity, known as a phantom limb, and up to 85% experience persistent and debilitating pain in the missing limb, termed phantom limb pain (hereafter PLP). We previously demonstrated that Virtual Reality (VR) with active leg movements and vision of a virtual limb significantly reduce phantom limb pain in subjects with below the knee amputations. The work proposed here has several objectives. In Specific Aim 1 we will randomize 40 subjects with PLP to treatment with our Active VR or a commercially available VR pain treatment (Cool!). In Specific Aim 2 we propose to develop a home intervention for PLP using the intervention (Active VR or Cool!) that in Specific Aim 1 proved to be most efficacious. In specific Aim 3 we will obtain multimodal ultra-high resolution (7T) MRI imaging in subjects with PLP before and after treatment, and normal subjects without amputation; we will also attempt to develop imaging biomarkers that predict efficacy of treatment. Imaging studies will address a number of controversies regarding the neural basis of PLP and explore human neuroplasticity more generally. Finally, in Specific Aim 4 we propose to determine factors that could be used in a clinical biomarker-based algorithm to predict response to home-based VR treatment. Using classification and regression tree (CART) analysis with the data from Aim 2, we will identify behavioral and neuroanatomic factors that predict treatment response. By the end of the grant period, we will have determined the relative efficacy of two VR treatments for PLP, assessed the feasibility and efficacy of a low-cost home-based treatment, determined the neuroanatomic changes associated with treatment response using advanced methods, and explored the behavioral and neuroimaging biomarkers predicting treatment response. These data will provide a critical step toward clinical implementation of a VR treatment protocol for PLP and will advance theoretical understanding of the mechanisms and functional neuroanatomy of PLP.