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. 2014 May 16;9(5):e97882.
doi: 10.1371/journal.pone.0097882. eCollection 2014.

Psychometric assessment of the Rat Grimace Scale and development of an analgesic intervention score

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Psychometric assessment of the Rat Grimace Scale and development of an analgesic intervention score

Vanessa Oliver et al. PLoS One. .

Abstract

Our limited ability to assess spontaneous pain in rodent models of painful human conditions may be associated with a translational failure of promising analgesic compounds in to clinical use. If measurement of spontaneous pain behaviours can be used to generate an analgesic intervention score their use could expand to guide the use of analgesics, as mandated by regulatory bodies and ethical and welfare obligations. One such measure of spontaneous pain, the Rat Grimace Scale (RGS), has recently been described and shown to exhibit reliability. However, reliability of measurement scores is context and content specific, and further testing required to assess translation to a heterogenous setting (different model, raters, environment). The objectives of this study were to perform reliability testing with the Rat Grimace Scale in a heterogenous setting and generate an analgesic intervention score for its use. In a randomised, blinded study, sixteen adult female rats received one of three analgesia treatments (0.05 mg/kg buprenorphine subcutaneously, 1 mg/kg meloxicam subcutaneously, 0.2 mg/kg oral buprenorphine in jelly) peri-operatively (telemetry unit implantation surgery). Rats were video-recorded (before, 1-6 and 12 hours post-operatively) and images collected for independent scoring by three blinded raters using the RGS, and five experts based on "pain/no pain" assessment. Scores were used to calculate inter- and intra-rater reliability with an intraclass correlation coefficient and generate an analgesic intervention score with receiver operating characteristic curve analysis. The RGS scores showed very good inter- and intra-rater reliability (0.85 [0.78-0.90 95% CI] and 0.83 [0.76-0.89], respectively). An analgesic intervention threshold of greater than 0.67 was determined. These data demonstrate that the RGS is a useful tool which can be successfully employed in a heterogenous setting, and has the potential to guide analgesic intervention.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Receiver operating characteristics (ROC) curve.
The optimal analgesic intervention score was >0.67, derived from a balance between the greatest values of sensitivity (84.6% [71.9–93.1]) and specificity (88.6% [73.3–96.8]. There was a significant difference in the area (0.94 [0.87–0.98], p<0.0001) under the calculated ROC curve compared with an AUC of 0.5 (representative of a non-discriminative test). n = 87 images
Figure 2
Figure 2. Scatter plot of Rat Grimace Scale scores categorised by “no pain” (0) and “pain” (1) assignment.
Images of rat faces were scored by expert raters and classified as “pain” or “no pain” based on subjective evaluation. The dashed horizontal line shows the analgesic intervention score of 0.68. There is clear overlap between the two assigned pain states, reflective of the balance in sensitivity and specificity. n = 87 images
Figure 3
Figure 3. Sham treatment group and the Rat Grimace Scale.
A significant overall effect of time was observed (p = 0.02) but differences between individual time points and baseline (time 0) were not significant. All RGS scores were below the analgesic intervention score of >0.67. Dashed horizontal line is set at RGS of 0.68. n = 9. Data are mean ± SEM.
Figure 4
Figure 4. Time course of Rat Grimace Scale (RGS) scores.
Pooled data (all treatment groups) show the expected increase in RGS post-operatively, followed by a decline at the 12 hour time point. n = 16. Data are mean ± SEM.

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Grants and funding

Daniel Pang was supported by an NSERC Discovery Grant. Vanessa Oliver was supported by the University of Calgary Faculty of Veterinary Medicine as part of the Investigative Medicine student rotation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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