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Systematic Review of Neuropathic Pain Models in Rodents (SRoNPMiR)

Systematic Review of Neuropathic Pain Models in Rodents (SRoNPMiR)

Background

Neuropathic pain is an increasingly prevalent pain disorder, which most of the treatments remains with mediocre efficacy. In preclinical in vivo research, qualitative and quantitative sex differences in pain signaling and relieve have been observed. Yet for decades, preclinical pain research has been biased towards the use of male animals in model establishment and drug efficacy studies (Mogil 2020). This is despite clinical and epidemiological evidence of equal or higher disease burden in female patients (van Hecke 2014).

The aim is by increasing attention to sex-sensitive research, to contribute to improvements in future translational validity of animal research (Yezierski 2018).

Objectives

Despite the availability of many single-sex study results and the increasing number of sex-stratified research results, to date, no sex-specific meta-analysis of preclinical neuropathic pain models exists. Characterizing the sex-specific baseline pain and post-operative evolvement of neuropathic pain in control groups is valuable to inform future mechanistic research question and for making sex-sensitive study design choices.

Methodology

This project consists of a meta-analysis and systematic review. For the meta-analysis, we will screen publications that have evolved since the establishment of the most prominent animal models of neuropathic pain affecting the sciatic nerve and extract measures for three widely used pain assays. We plan to derive meta-analytically sex-specific pain trajectories by neuropathic pain model and pain assay. We will use Bayesian modelling with ordinal predictors to develop models with and without sex as a factor, to check better model fit. In the systematic review part of this project, we focus on how developing research questions, designing experiments, analyzing and presenting results reflects the integration of sex as a biological variable in preclinical neuropathic pain research.

Expected results / Implications / Perspectives

From a 3R perspective, it will help to integrate the cumulative evidence on pain trajectories into sex-specific analgesic treatment & welfare assessment of animals (Smith 2019, Sadler 2022). In accordance with recent publications on methodological challenges in the inclusion of sex as a biological variable (Garcia-Sifuentes and Maney 2021), we aim to expose different layers of conducting sex-sensitive research and identify important research and reporting gaps.

Silke Kniffert, MSc

Research fellow - FORR

ORCID

Contact information
Phone:+49 30 450 543 667
E-mail:silke.kniffert@bih-charite.de