Neuromodulation: Overview

Neuromodulation: Technology at the Neural Interface is the preeminent journal in the area of neuromodulation, providing our readership with the state of the art clinical, translational and basic science research in our field and representing the needs of the broad neuromodulation community. For clinicians, engineers, scientists and members of the biotechnology industry alike, Neuromodulation provides timely and rigorously peer reviewed articles on the technology, science and clinical application of devices that interface with the nervous system to treat disease and improve function. Neuromodulation covers an ever expanding field including pain, headache, movement disorders, spasticity, paralysis, psychiatric disorders, epilepsy, sensory deprivation, gastric dysfunction, obesity and incontinence.

Abstract
Virtual reality-delivered psychological therapies have recently been investigated as non-pharmacological management for acute and chronic pain. However, no virtual reality pain therapy software existed that met the needs of cancer patients with neuropathic pain. We created a bespoke virtual reality-delivered pain therapy software programme to help cancer patients manage neuropathic pain incorporating guided visualisation and progressive muscle relaxation techniques, whilst minimising the risk of cybersickness in this vulnerable patient population. This randomised controlled pilot study evaluated the feasibility, acceptability, recruitment rates and risk of cybersickness of this pain therapy software programme. Clinical outcomes including opioid consumption, pain severity, pain interference and global quality of life scores were secondary aims. Of 87 eligible cancer patients with neuropathic pain, 39 were recruited (47%), allocated to either the intervention (20 patients, virtual reality pain therapy software programme) or control (19 patients, viewing virtual reality videos). Four patients withdrew before the 3-month follow-up (all in the control group). Pre-existing dizziness (Spearman ρ 0.37, p = 0.02) and pre-existing nausea (Spearman ρ 0.81, p < 0.001) were significantly associated with risk of cybersickness in both groups. Patients in the intervention group reported less cybersickness, as well as tolerated and completed all therapy sessions. At 1- and 3-month follow-up, there were trends in the intervention group towards reductions in: oral morphine equivalent daily dose opioid consumption (-8 mg and -4 mg; vs. control: 0 mg and +15 mg respectively); modified Brief Pain Inventory pain severity (-0.4, -0.8; vs. control +0.4, -0.3); and pain interference (-0.9, -1.8; vs. control -0.2, -0.3) scores. The global quality of life subscale from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 was not significantly changed between groups at 1 and 3 months (intervention: -5, -8; vs. control: +3, +4). This newly created virtual reality-delivered pain therapy software programme was shown to be feasible and acceptable to cancer patients with neuropathic pain. These results will aid the design of a definitive multicentre randomised controlled trial.

Abstract
This preclinical systematic review aimed to determine the effectiveness of different types and doses of exercise on pain behaviour and biomarkers in preclinical models of focal neuropathic pain. We searched MEDLINE, EMBASE, Web of Science, PubMed, SCOPUS, CINAHL and Cochrane library from inception to November 2022 for preclinical studies evaluating the effect of exercise compared to control interventions on neuropathic pain behaviour after experimental sciatic nerve injury. If possible, data were meta-analysed using random effect models with inverse-variance weighting. Thirty-seven studies were included and 26 meta-analysed. Risk of bias (SYRCLE tool) remained unclear in most studies and reporting quality (CAMARADES) was variable. Exercise reduced mechanical (SMD 0.53 (95% CI 0.31, 0.74), p= 0.0001, I2=0%, n=364), heat (0.32 (0.07,0.57), p=0.01, I2=0%, n=266) and cold hypersensitivity (0.51 (0.03, 1.0), p=0.04, I2=0%, n=90) compared to control interventions. No relationship was apparent between exercise duration or intensity and antinociception. Exercise modulated biomarkers related to different systems (e.g., immune system, neurotrophins). Whereas firm conclusions are prevented by the use of male animals only, variable reporting quality and unclear risk of bias in many studies, our results suggest that aerobic exercise is a promising tool in the management of focal neuropathic pain. Registration PROSPERO CRD42021231286. Perspective: This systematic review and meta-analysis demonstrates that aerobic exercise reduces neuropathic pain-related behavior in preclinical models of sciatic nerve injury. This effect is accompanied by changes in biomarkers associated with inflammation and neurotrophins among others. These results could help to develop exercise interventions for patients with neuropathic pain.