Efficacy and Mechanisms of Virtual Reality Treatment of Phantom Leg Pain

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.

Grant Number: 5R01HD104158-05
NIH Institute/Center: NIH
Principal Investigator: LAUREL BUXBAUM