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.

An amygdalo-parabrachial pathway regulates pain perception and chronic pain

“…We used a rodent model of neuropathic pain, evoked by chronic constriction of the infraorbital nerve (CCI-ION) (Vos et al, 1994;Benoist et al, 1999;Okubo et al, 2013;Akintola et al, 2017;Castro et al, 2017a). We first anesthetized animals with isoflurane, followed by ketamine/xylazine (i.p.).…”

“…To assess ongoing pain, we analyzed facial grimace behavior (Langford et al, 2010;Sotocinal et al, 2011;Akintola et al, 2017Akintola et al, , 2019. We placed animals in a square Plexiglas™ chamber (6×8 inches for rats, 3x5 inches for mice) with two opaque sides and two transparent sides on a raised wire platform.…”

“…The grimace scale quantifies changes in four action units: orbital tightening, nose-cheek bulge, whisker tightening and ear position. We selected ten screenshots for each animal or each time point (during within-subject and repeated measures tests), and on each image, each action unit was given a score of 0, 1, or 2, as previously described (Langford et al, 2010;Sotocinal et al, 2011;Akintola et al, 2017Akintola et al, , 2019. We calculated mean grimace scale scores as the average score across all the action units.…”

The Utility of Iris-pupillary Area Ratio as a Non-invasive Index of Stress in Primates

“…One of the potential applications of I/P ratio analysis could be in laboratory animal welfare, where currently the grimace scale is used to measure the degree of pain/stress. [38][39][40][41][42][43] I/P ratio analysis could be integrated to grimace scale scores to refine the efficiency and sensitivity of progressively detecting animal in pain/stress. Although this study was focused on primates, we see the general principle of this work is applicable to all species.…”

Placebo Analgesia in Rodents: Current and Future Research

“…To allow reliable and reproducible quantification of pain-related expressions, Mogil and collaborators developed facial grimace scales for mice (Langford et al, 2010) and for rats (Sotocinal et al, 2011) and demonstrated that these objective metrics have high accuracy and reliability for detecting ongoing pain of relatively short duration (minutes to hours). This approach has been shown to be a reliable and sensitive metric for the assessment of ongoing pain in a rodent model of chronic, trigeminal neuropathic pain in both rats and mice (Akintola et al, 2017). With these experimental components in hand, it would be possible to set out to test the hypothesis that placebo analgesia can be conditioned in animals suffering from chronic pain.…”