Virtual Walking to Reduce Chronic Neuropathic Pain in Subjects With SCI

Overview

About 70% of people with a spinal cord injury in Switzerland have chronic pain that lasts more than 3 to 6 months. This pain can be caused by muscle or joint problems, or by nerve damage (neuropathic pain). Neuropathic pain is often hard to treat, and current treatments may cause side effects or not work well. This study will test whether virtual walking from different visual perspectives can reduce chronic neuropathic pain and improve quality of life after spinal cord injury. We will also compare which perspective works best. To better understand how the training works, we will use two tests-quantitative sensory testing (QST) and contact heat-evoked potentials (CHEPs)-to measure changes in the pain and nerve systems.

Chronic pain conditions are highly prevalent in the Swiss spinal cord injury (SCI) population with a prevalence of 73% (Müller et al., 2017). Most of those individuals show multiple pain modalities (neuropathic, nociceptive and unknown pain type) (Mahnig et al., 2016; Siddall et al., 2003). For example, Mahnig et al. (2016) reported prevalences of 79% neuropathic and 61% nociceptive pain in individuals with SCI seen in a pain clinic. The current practice of pharmacological first- and second-line treatments comes along with many side effects and unsatisfactory results (Finnerup et al., 2015). This is because the underlying biology of chronic neuropathic pain (NeP) and the mechanisms that lead to chronification of pain are highly complex and not fully understood. Latest research suggests that chronification of pain is associated with anatomical and functional reorganization of the brain (Reckziegel et al., 2019; Wrigley et al., 2009). More specifically, cortical grey matter density changes and neuroanatomical reorganization of the primary somatosensory cortex are discussed as factors associated with pain chronification. Additional mechanisms proposed to explain NeP after SCI include spinal cord plasticity, supraspinal reorganization, and increased neuronal excitability of dorsal horn neurons (Finnerup, 2013). MRI data show, that there is a correlation between the grade of cortical reorganisation and pain intensity in people with complete SCI (Gustin et al., 2023). However, it is unclear whether there is a systematic influence of the severity of the SCI lesion, graded by the American Spinal Injury Association (ASIA) Impairment Scale (complete or incomplete SCI), on pain intensity. Alongside with studies about pain mechanisms and improved pharmaceutical treatment, non-invasive and non-pharmacological alternative treatments with minimal side effects have been investigated, such as, for example virtual reality (VR). Changes of pain perception due to VR interventions in individuals with neuropathic spinal cord injury pain (SCIP) are described in the literature (Eick \& Richardson, 2015; Kumru et al., 2013; Moseley, 2007; Özkul et al., 2015; Soler et al., 2010; Trost et al., 2022). Recent reviews have shown good short-term effects of VR in the treatment of SCIP (Chi et al., 2019; de Araújo et al., 2019). However, there is lack of evidence from randomized controlled trials. Chronic pain in SCI is often modulated by psycho-social factors such as depression, anxiety, extent of social support and pain catastrophising (Braunwalder et al., 2022; Braunwalder et al., 2021; Müller et al., 2017; Wollaars et al., 2007). Data about the influence of psycho-social factors on VR therapy are only reported for VR therapy in first person perspective (Trost et al., 2022). Data about the influence of psycho-social factors third person perspective are not available. Recently, a virtual walking (VW) treatment protocol in third person perspective inclusive an additional haptic feedback modality (controlled movement of the wheelchair seat to improve the walking immersion) has been set up and evaluated within a feasibility study with individuals with SCIP, reporting a high level of satisfaction and acceptance of the VW procedure at the Centre for Pain Medicine, Swiss Paraplegic Centre (SPC), Nottwil. In this uncontrolled explorative trial, there was a tendency towards reduced pain intensity and spread of reported pain after VW (Aerni, 2020). To better understand individual responses to VR and explore underlying pain mechanisms, neurophysiological assessments such as quantitative sensory testing (QST) and contact heat-evoked potentials (CHEPs) are used as biomarkers to identify sensory phenotypes. To address the challenges of assessing and treating pain following SCI, the systematic evaluation of all somatosensory submodalities is strongly recommended for both pathophysiological research and treatment trials in individuals with SCI-related pain (Finnerup, 2013). Landmann et al. (2024) demonstrated that QST can identify distinct sensory phenotypes in individuals with neuropathic spinal cord injury pain (SCIP). Furthermore, the combination of QST and CHEPs enables objective and standardized measurement of sensory system alterations, thereby contributing to a better understanding of underlying mechanisms (Opsommer et al., 2021). The aim of the present study is to evaluate (1) the efficiency of the standardised VW-setting with regard to pain reduction in subjects with complete and incomplete SCI, (2) bio-psycho-social prognostic factors which may influence the efficacy of VR, and (3) the influence of VR on psycho-social characteristics of subjects with SCI and (4) to identify pain and sensory phenotypes in individuals with SCIP and examine whether these phenotypes are associated with differential effects of VR on pain reduction..