A systematic review and meta-analysis of the effect of experimental pain on rat grimace scale scores

The rat grimace scale (RGS) purports to assess behavioural responses related to pain by assessing four facial expressions. To understand how experimental pain affects RGS scores, we conducted a systematic review of studies which reported outcomes using this scale ( CRD42022292189 ). Systematic searches were conducted on 3 databases in January 2022. RGS studies that assessed the effects of disease models relating to pain were included. Risk of bias was assessed by using a modified version of the CAMARADES reporting checklist and SYRCLE Risk of Bias tool. A standardised mean difference effect size was calculated using a random-effects model. Fifty-four studies were included, in which 15 disease model classes and 16 classes of pharmacological interventions were identified. RGS scores were increased in disease models hypothesised to be associated with persistent pain (SMD = −4.44 [95%CI −6.25 to −2.63]) and this response was attenuated by analgesic drugs (SMD = 1.97 [95%CI 1.25 to 2.69]). Post-surgical models (39% of experiments) and opioids (30% of experiments) were the most commonly reported. We could not ascertain the sources of heterogeneity due to insufficient data. Most studies were assessed as having an unclear risk of bias due to poor reporting quality. The relationship between RGS scores and mechanically evoked limb withdrawal was inconsistent. These findings indicate emerging evidence to support the use of RGS in persistent pain research, but additional research is needed to strengthen these findings. Future studies could benefit from using sex-balanced animal populations with diverse genetic backgrounds. To enhance the impact and reproducibility of their findings, studies should prioritise improvements in reporting quality.