Behavioral outcome measures in preclinical rodent models for postoperative pain: A protocol for a systematic review and quantitative meta-analysis

Abstract

Background Understanding the (patho-) physiology of pain after surgery is incomplete; this hampers the effective treatment and leads to long-term consequences, including complications, chronification of pain, and potential drug misuse. Evidence-based research is essential to discover novel therapeutic options. Rodent models for postoperative pain have been developed to widen the knowledge about mechanisms and improve translation. These models cause evoked and non-evoked pain-related behaviors with specific duration, intensity, and timing expressions but with differences between studies. Reasons are heterogeneously performed (and/or reported) behavioral assays making it challenging to compare results across studies. Furthermore, indices about the influencing role of animal-related factors like age, sex, or the experimental setting are given. However, most of them were not systematically investigated, e.g., for pain-related behavior in rodent models of postoperative pain. Therefore, this review will systematically examine pain-related behaviour in different postoperative models in rodents. Acquisition of publication and experimental level characteristics will identify possible confounding and multilevel bias factors on results. Methods Four databases will be screened, and results will be compared for duplicates by automated and manual screening. Publication and experimental level characteristics will be extracted to (1) determine methodological aspects and use frequency of postoperative pain models and pain-related behavioral outcomes, (2) generate model-dependent behavior profiles, and (3) identify and critically evaluate confounder and bias factors on outcome measures and results. Discussion Findings from this study are necessary to inform researchers and improve future studies in design, performance, analysis, and ethical and translational aspects. Systematic review registration: Submitted to PROSPERO