The grimace scale reliably assesses chronic pain in a rodent model of trigeminal neuropathic pain

Abstract

The limited success in translating basic science findings into effective pain management therapies reflects, in part, the difficulty in reliably assessing pain in experimental animals. This shortcoming is particularly acute in the field of chronic, ongoing pain. Quantitative analysis of facial expressions-the grimace score-was introduced as a promising tool, however, it is thought to reliably assess only pain of short or medium duration (minutes to hours). Here, we test the hypothesis that grimace scores are a reliable metric of ongoing neuropathic pain, by testing the prediction that chronic constriction injury of the infraorbital nerve (CCI-ION) will evoke significant increases in grimace scale scores. Mice and rats were subjected to CCI-ION, and tested for changes in mechanical hypersensitivity and in grimace scores, 10 or more days after surgery. Both rats and mice with CCIION had significantly higher grimace scores, and significantly lower thresholds for withdrawal from mechanical stimuli applied to the face, compared to sham-operated animals. Fentanyl reversed the changes in rat grimace scale scores, suggesting that these scores reflect pain perception. These findings validate the grimace scale as a reliable and sensitive metric for the assessment of ongoing pain in a rodent model of chronic, trigeminal neuropathic pain.

Keywords: Behavior; Chronic pain; Constriction nerve injury; Pain metrics.

Fig. 1

CCI-ION significantly reduces mechanical withdrawal thresholds, in both rats (left) and mice (right). For rats, filled circles are data collected 27 days after CCI, and open circles are data collected 10 days after CCI. Group data are shown as medians with 95% confidence intervals.

Fig. 2

CCI-ION significantly increases grimace scale scores in both rats (above) and mice (below). Group data are shown as medians with 95% confidence intervals. For rats, filled circles are data collected 27 days after CCI, and open circles are data collected 10 days after CCI. Fentanyl administration, in rats, significantly reduced grimace scores. Sample images for each species are shown on the right.