Background: Virtual reality (VR) is a computer technology that immerses a user in a completely different reality. The application of VR in acute pain settings is well established. However, in chronic pain, the applications and outcome parameters influenced by VR are less clear.Objective: This review aimed to systematically identify all outcome parameters that are reported in relation to VR in patients with chronic pain.Methods: A total of 4 electronic databases (PubMed, Scopus, Web of Science, and Embase) were searched for relevant studies. Multilevel random-effect meta-analyses were performed, whereby the standardized mean difference was chosen as the effect size to denote the difference between measurements before and after a VR intervention.Results: The initial database search identified 1430 studies, of which 41 (2.87%) were eventually included in the systematic review. Evidence has been found for the effects of VR on pain, functioning, mobility, functional capacity, psychological outcomes, quality of life, neuropsychological outcomes, and physical sensations. The overall effect size (a total of 194 effect sizes from 25 studies) based on a three level meta-analysis was estimated at 1.22 (95% CI 0.55-1.89; z=3.56; P<.001), in favor of improvements after a VR intervention. When categorizing effect sizes, the overall effect sizes were reported as follows: 1.60 (95% CI 0.83-2.36; z=4.09; P<.001) for the effect of VR on pain (n=31), 1.40 (95% CI 0.13-2.67; z=2.17; P=.03) for functioning (n=60), 0.49 (95% CI −0.71 to 1.68; z=0.80; P=.42) for mobility (n=24), and 0.34 (95% CI −1.52 to 2.20; z=0.36; P=.72) for functional capacity (n=21).Conclusions: This systematic review revealed a broad range of outcome variables influenced by an intervention of VR technology, with statistically significant pain relief and improvements in functioning. These findings indicate that VR not only has applications in acute pain management but also in chronic pain settings, whereby VR might be able to become a promising first-line intervention as complementary therapy for patients with chronic pain.Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42021227016; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=227016

Central sensitization is a form of maladaptive neuroplasticity underlying many chronic pain disorders, including neuropathic pain, fibromyalgia, whiplash, headache, chronic pelvic pain syndrome and some forms of osteoarthritis, low back pain, epicondylitis, shoulder pain and cancer pain. Brain-derived neurotrophic factor (BDNF) is a driving force behind neuroplasticity, and it is therefore crucial for neural maintenance and repair. However, BDNF also contributes to sensitization of pain pathways, making it an interesting novel therapeutic target. An overview of BDNF's sensitizing capacity at every level of the pain pathways is presented, including the peripheral nociceptors, dorsal root ganglia, spinal dorsal horn neurons, and brain descending inhibitory and facilitatory pathways. This is followed by the presentation of several potential therapeutic options, ranging from indirect influencing of BDNF levels (using exercise therapy, anti-inflammatory drugs, melatonin, repetitive transcranial magnetic stimulation) to more specific targeting of BDNF's receptors and signaling pathways (blocking the proteinase-activated receptors 2-NK-κβ signaling pathway, administration of phencyclidine for antagonizing NMDA receptors, or blockade of the adenosine A2A receptor). This section focuses on combining pharmacotherapy with multimodal rehabilitation for balancing the deleterious and therapeutic effects of BNDF treatment in chronic pain patients, as well as accounting for the complex and biopsychosocial nature of chronic pain.

Chronic spinal pain, including both neck and low back pain, is a common disabling disorder in which sleep problems are frequently reported as a comorbidity. The complex processes of both sleep and chronic pain seem to have overlapping mechanisms, which may explain their often established bidirectional relationship. This systematic review aims to investigate the assumed association between sleep and chronic spinal pain by providing an overview of the literature from the last decade. Eligible studies were obtained by searching four databases (PubMed, Embase, Web of Science, and PsycARTICLES). Articles were found relevant if they included a human adult population and investigated the possible association between sleep parameters and chronic spinal pain. Only studies published after January 2009 were included, as this review aimed to provide an update of a previous literature overview on this topic. The quality of the studies was assessed by risk of bias and level of evidence. A total of twenty-seven studies (6 cohort, 5 case-control, and 16 cross-sectional studies) were included in this systematic review. The methodological quality of these studies was low to moderate. The majority of studies reported weak to moderate evidence for an association between sleep parameters and chronic spinal pain, with more severe pain accompanied by more disturbed sleep. Addressing frequently reported sleep problems in chronic spinal pain patients therefore appears to be a necessary complement to pain management to achieve optimal treatment outcomes.

Background and Purpose—: Insulin-like growth factor I (IGF-I) is neuroprotective in animal models of stroke. We investigated whether serum IGF-I levels in patients with acute ischemic stroke influence stroke severity and outcome. Methods—: Concentrations of IGF-I and IGF binding protein 3 were measured in serum samples obtained within 6 hours after stroke onset from 255 patients who took part in the placebo arm of the United States and Canadian Lubeluzole in Acute Ischemic Stroke Study. Stroke severity was assessed with the National Institutes of Health Stroke Scale. Multivariate analysis was performed to assess the overall shift in modified Rankin Scale score and changes in the National Institutes of Health Stroke Scale score at 3 months. Survival curves were plotted using the Kaplan-Meier method, and the Cox proportional hazard model was used for multivariate analysis to investigate factors influencing survival. Results—: After controlling for statistically relevant risk factors, subjects with high IGF-I levels or IGF-I/IGF binding protein 3 ratios had a better neurological and functional outcome at 3 months. Baseline stroke severity was not different between high and low IGF-I groups. In contrast to the low IGF-I group, neurological symptoms gradually improved from Day 3 in the high IGF-I group. Conclusions—: Our results suggest that high serum IGF-I levels just after ischemic stroke onset are associated with neurological recovery and a better functional outcome.