Chronic postsurgical pain (CPSP) is a significant detriment to post-surgical recovery and a risk factor for prolonged opioid use. Emerging evidence suggests the estimated heritability for chronic pain is 45% and that genetic factors partially explain individual susceptibility to CPSP. The aim of this study was to systematically review, assess quality and summarize the studies in humans that have investigated genetic factors associated with CPSP. We also conducted a meta-analysis to derive a single effect size for evaluable genetic associations with CPSP. Our comprehensive literature search included review of 21 full-text articles evaluating variants of 69 genes for association with CPSP. We found significant gene variant associations reported for variants/ haplotypes of 26 genes involved in neurotransmission, pain signaling, immune responses and neuroactive ligand-receptor interaction, with CPSP. Six variants of five genes (COMT: rs4680 and rs6269, OPRM1: rs1799971, GCH1: rs3783641, KCNS1: rs734784 and TNFA: rs1800629), were evaluated by more than one study and were included in the meta-analysis. At rs734784 (A>G) of KCNS1, presence of G allele marginally increased risk of CPSP (Additive genetic model; Odds ratio: 1.511; 95% CI 1 to 2.284; p-value 0.050), while the other variants did not withstand metaanalyses criteria. Our findings demonstrate the role of genetic factors with different functions in CPSP, and also emphasize that single genetic factors have small effect sizes in explaining complex conditions like CPSP. Heterogeneity in surgical cohorts, population structure and outcome definitions, as well as small number of available studies evaluating same variants, limit the metaanalysis. There is a need for large-scale, homogenous, replication studies to validate candidate genes, and understand the underlying biological networks underpinning CPSP.

Background Distraction-based therapies, such as virtual reality (VR), have been used to reduce pain during acutely painful procedures. However, distraction alone cannot produce prolonged pain reduction to manage sustained postoperative pain. Therefore, the integration of VR with other pain-reducing therapies, like guided relaxation, may enhance its clinical impact. Objective The goal of this pilot study was to assess the impact of a single guided relaxation–based VR (VR-GR) session on postoperative pain and anxiety reduction in children. We also explored the influence of pain catastrophizing and anxiety sensitivity on this association. Methods A total of 51 children and adolescents (7-21 years) with postoperative pain and followed by the Acute Pain Service at Cincinnati Children’s Hospital were recruited over an 8-month period to undergo a single VR-GR session. Prior to VR, the patients completed 2 questionnaires: Pain Catastrophizing Scale for Children (PCS-C) and the Child Anxiety Sensitivity Index (CASI). The primary outcome was a change in pain intensity following the VR-GR session (immediately, 15 minutes, and 30 minutes). The secondary outcomes included changes in pain unpleasantness and anxiety. Results The VR-GR decreased pain intensity immediately (P<.001) and at 30 minutes (P=.04) after the VR session, but not at 15 minutes (P=.16) postsession. Reductions in pain unpleasantness were observed at all time intervals (P<.001 at all intervals). Anxiety was reduced immediately (P=.02) but not at 15 minutes (P=.08) or 30 minutes (P=.30) following VR-GR. Patients with higher CASI scores reported greater reductions in pain intensity (P=.04) and unpleasantness (P=.01) following VR-GR. Pain catastrophizing was not associated with changes in pain and anxiety. Conclusions A single, short VR-GR session showed transient reductions in pain intensity, pain unpleasantness, and anxiety in children and adolescents with acute postoperative pain. The results call for a future randomized controlled trial to assess the efficacy of VR-GR. Trial Registration ClinicalTrials.gov NCT04556747; https://clinicaltrials.gov/ct2/show/NCT04556747

Objective Virtual reality (VR) is a promising method to manage pain. Distraction-based VR (VR-D) is thought to reduce pain by redirecting attention. While VR-D can reduce pain associated with acutely painful procedures, it is unclear if VR-D can reduce pain after surgery. We assessed the ability of a single VR-D session to decrease postoperative pain and anxiety and explored if pain catastrophizing and anxiety sensitivity influenced these outcomes in children following surgery. Design Single-center, prospective, pilot study Setting Cincinnati Children’s Hospital Medical Center (CCHMC) Subjects 50 children (7-21 years) with postoperative pain followed by the Acute Pain Service Methods Patients received one VR-D session following surgery. Prior to the session, patients completed pain catastrophizing (PCS-C) and anxiety sensitivity (CASI) questionnaires. Primary outcome consisted of changes in pain intensity following VR-D (immediately, 15, and 30 minutes). Secondary outcomes included changes in pain unpleasantness and anxiety. Results VR-D use was associated with a decrease in pain intensity immediately and 15-minutes after VR-D. Reductions in pain unpleasantness were observed up to 30 minutes following VR-D. VR-D was also associated with a reduction in anxiety immediately and at 15-minutes. While patients with higher pain catastrophizing had higher baseline pain intensity and unpleasantness, they did not show larger pain reductions following VR-D compared to those with lower pain catastrophizing. Conclusions VR-D may be beneficial in transiently reducing pain intensity, unpleasantness, and anxiety in children with postoperative pain. This study informs design of larger, randomized, controlled study assessing VR-D for acute postoperative pain and anxiety management.

IntroductionVirtual reality (VR) offers an innovative method to deliver non-pharmacological pain management. Distraction-based VR (VR-D) using immersive games to redirect attention has shown short-term pain reductions in various settings. To create lasting pain reduction, VR-based strategies must go beyond distraction. Guided relaxation-based VR (VR-GR) integrates pain-relieving mind–body based guided relaxation with VR, a novel therapy delivery mechanism. The primary aim of this study is to assess the impact of daily VR-GR, VR-D and 360 video (passive control) on pain intensity. We will also assess the impact of these interventions on pain unpleasantness, anxiety and opioid and benzodiazepine consumption. The secondary aim of this study will assess the impact of psychological factors (anxiety sensitivity and pain catastrophising) on pain following VR.Methods and analysisThis is a single centre, prospective, randomised, clinical trial. Ninety children/adolescents, aged 8–18 years, presenting for Nuss repair of pectus excavatum will be randomised to 1 of 3 study arms (VR-GR, VR-D and 360 video). Patients will use the Starlight Xperience (Google Daydream) VR suite for 10 min. Patients randomised to VR-GR (n=30) will engage in guided relaxation/mindfulness with the Aurora application. Patients randomised to VR-D (n=30) will play 1 of 3 distraction-based games, and those randomised to the 360 video (n=30) will watch the Aurora application without audio instructions or sound. Primary outcome is pain intensity. Secondary outcomes include pain unpleasantness, anxiety and opioid and benzodiazepine consumption.Ethics and disseminationThis study follows Standard Protocol Items: Recommendations for Interventional Trials guidelines. The protocol was approved by the Cincinnati Children’s Hospital Medical Center’s institutional review board. Patient recruitment began in July 2020. Written informed consent will be obtained for all participants. All information acquired will be disseminated via scientific meetings and published in peer-reviewed journals.Trial registration numberNCT04351776.