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. 2011 Jul 29:7:55.
doi: 10.1186/1744-8069-7-55.

The Rat Grimace Scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions

Susana G Sotocinal  1 , Robert E Sorge, Austin Zaloum, Alexander H Tuttle, Loren J Martin, Jeffrey S Wieskopf, Josiane C S Mapplebeck, Peng Wei, Shu Zhan, Shuren Zhang, Jason J McDougall, Oliver D King, Jeffrey S Mogil
Affiliations

The Rat Grimace Scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions

Susana G Sotocinal et al. Mol Pain. .

Abstract

We recently demonstrated the utility of quantifying spontaneous pain in mice via the blinded coding of facial expressions. As the majority of preclinical pain research is in fact performed in the laboratory rat, we attempted to modify the scale for use in this species. We present herein the Rat Grimace Scale, and show its reliability, accuracy, and ability to quantify the time course of spontaneous pain in the intraplantar complete Freund's adjuvant, intraarticular kaolin-carrageenan, and laparotomy (post-operative pain) assays. The scale's ability to demonstrate the dose-dependent analgesic efficacy of morphine is also shown. In addition, we have developed software, Rodent Face Finder®, which successfully automates the most labor-intensive step in the process. Given the known mechanistic dissociations between spontaneous and evoked pain, and the primacy of the former as a clinical problem, we believe that widespread adoption of spontaneous pain measures such as the Rat Grimace Scale might lead to more successful translation of basic science findings into clinical application.

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Figures

Figure 1
Figure 1
Uncropped image identified by RFF for RGS scoring. Boxes: blue, total region analyzed; red, detected eye; green, detected ear; purple, estimated face region.
Figure 2
Figure 2
The four action units of the Rat Grimace Scale (RGS). See text for details.
Figure 3
Figure 3
Interrater reliability (a) and accuracy (b) of the RGS in the quantification of pain. In both cases 100 photographs were scored, half pain (CFA) and half no pain (baseline). Scorer 1 developed the RGS, and trained the others; the signal detection data represent the average of all six scorers. Hits: pain photograph scored as pain; Correct Rejections: no pain photograph scored as no pain; Misses: pain photograph scored as no pain; False Alarms: no pain photograph scored as pain. ICC: intraclass correlation coefficient (see text).
Figure 4
Figure 4
Quantification of spontaneous pain in three nociceptive assays: intraplantar CFA (a), intraarticular kaolin/carrageenan (b), and postoperative (laparotomy) pain (c). Bars represent mean ± SEM RGS score (n = 6-10 rats/assay). *p< 0.05; **p< 0.01 compared to baseline (Bonferroni-corrected).
Figure 5
Figure 5
Prominence of individual action units at the peak of apparent spontaneous pain in each assay (see Figure 4). Bars represent mean ± SEM difference scores (pain - no pain; n = 23 rats). Overall, all action units were equally prominent statistically (a), and this was also true in each assay considered separately (b). **p< 0.01 (Bonferroni-corrected) compared to other assays. K/C = kaolin/carrageenan.
Figure 6
Figure 6
Quantification of morphine analgesia by the RGS. Morphine was administered 5.5 h after CFA and 15 min before the start of 30-min digital video recording. Bars represent ± SEM RGS score (n = 4-10 rats/dose). *p< 0.05 compared to saline (0) by Dunnett's case-comparison posthoc test (one-way).
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