Concurrent Validation of MI-CAT(V), a Clinical Metrology Instrument for Veterinarians Assessing Osteoarthritis Pain in Cats, through Testing for Firocoxib Analgesic Efficacy in a Prospective, Randomized, Controlled, and Blinded Study.

Veterinarians face the lack of a rapid, reliable, inexpensive, and treatment-sensitive metrological instrument reflecting feline osteoarthritis (OA) pain. The Montreal Instrument for Cat Arthritis Testing, for Use by Veterinarians (MI-CAT(V)) has been refined in 4 sub-sections, and we proposed its concurrent validation. Cats naturally affected by OA (n = 32) were randomly distributed into 4 groups of firocoxib analgesic (Gr. A: 0.40; B: 0.25; C: 0.15, and P: 0.00 mg/kg bodyweight). They were assessed during Baseline, Treatment, and Recovery periods using MI-CAT(V) and objective outcomes (effort path, stairs assay compliance, and actimetry). The MI-CAT(V) total score correlated to the effort path and actimetry (RhoS = -0.501 to -0.453; p < 0.001), also being sensitive to treatment responsiveness. The pooled treatment group improved its total, gait, and body posture scores during Treatment compared to the Baseline, Recovery, and placebo group (p < 0.05). The MI-CAT(V) suggested a dose-(especially for Gr. B) and cluster-response. Cats in the moderate and severe MI-CAT(V) clusters responded to firocoxib with a remaining analgesic effect, while the mild cluster seemed less responsive and experienced a negative rebound effect. The MI-CAT(V) was validated for its OA pain severity discriminatory abilities and sensitivity to firocoxib treatment, providing a new perspective for individualized care.

Pre-warming following premedication limits hypothermia before and during anesthesia in Sprague-Dawley rats (Rattus norvegicus).

In humans and other mammals, general anesthesia impairs thermoregulation, leading to warm core blood redistributing to the periphery. This redistribution is an important contributor to hypothermia that can be reduced with pre-warming before anesthesia. Additionally, sedation following premedication has been associated with hypothermia in dogs. In a prospective, randomized, cross-over study, 8 adult male and female rats (weighing 388 to 755 g) were sedated with intramuscular ketamine-midazolam-hydromorphone, then placed in an unwarmed cage or warmed box for 14 minutes, followed by 30 minutes of isoflurane anesthesia with active warming. Core body temperature was monitored throughout. After sedation, warmed rats gained 0.28°C ± 0.13°C and unwarmed rats lost 0.19°C ± 0.43°C, a significant difference between groups (P = 0.004). After anesthesia, warmed rats maintained higher core temperatures (P < 0.0001) with 2/8 and 6/8 of warmed and unwarmed rats becoming hypothermic, respectively. Pre-warming during sedation and active warming during general anesthesia is effective in minimizing hypothermia.

Chez l'humain et les autres mammifères, l'anesthésie générale perturbe la thermorégulation, menant au sang chaud interne se redistribuant vers la périphérie. Cette redistribution est une composante majeure de l'hypothermie et peut être réduite par le réchauffement préemptif. De plus, la sédation suivant la prémédication a été associé à l'hypothermie chez les chiens. Dans cette étude prospective, randomisée et croisée, 8 rats adultes mâles et femelles (388 à 755 g) ont été sédationnés avec ketamine-midazolam-hydromorphone au niveau intramusculaire puis placés dans une cage non-chauffée ou une boîte réchauffée durant 14 minutes, suivi d'une période d'anesthésie générale de 30 minutes sur tapis chauffant. La température interne a été suivi tout au long de l'expérimentation. Après la sédation, les rats réchauffés ont gagné 0,28 °C ± 0,13 °C alors que les rats non-réchauffés ont perdu 0,19 °C ± 0,43 °C, une différence significative entre les groupes (P = 0,004). Après l'anesthésie, les rats réchauffés ont maintenu une température interne supérieure (P < 0,0001) avec 2/8 et 6/8 des rats réchauffés et non-réchauffés hypothermes, respectivement. Le réchauffement préemptif durant la sédation suivi de réchauffement actif durant l'anesthésie générale est efficace pour minimiser l'hypothermie.(Traduit par les auteurs).

Aversion to Desflurane and Isoflurane in Sprague-Dawley Rats (Rattus Norvegicus).

Carbon dioxide and isoflurane are widely used for killing rats, yet may not truly achieve "euthanasia", because they elicit aversion. The inhalant anesthetic desflurane is faster acting than isoflurane, representing a potential refinement. Using an aversion-avoidance paradigm, 24 rats were exposed to isoflurane or desflurane (n = 12 per group) at initial exposure. Fourteen rats were then re-exposed to isoflurane or desflurane (n = 7 per group), after a 7 days washout period. Initial exposure: time to recumbency was faster for desflurane than isoflurane (p = 0.0008, 95% CI [-12.9 to 32.6 s]), with 9/12 and 6/12 rats becoming recumbent, respectively. At initial exposure, there was no difference between groups in time to withdrawal (p = 0.714). At re-exposure, all rats withdrew and no rats became recumbent. Time to withdrawal at re-exposure did not differ between treatment groups (p = 0.083). Compared to initial exposure, time to withdrawal during re-exposure was similar for isoflurane (p = 0.228) and faster with desflurane (p = 0.012, 95% CI [19.1 to 49.5 s]). Isoflurane and desflurane are similarly aversive, with aversion increasing at re-exposure. The shorter time from exposure to recumbency with desflurane indicates that any distress is of a shorter duration when compared with isoflurane.

Pre-warming before general anesthesia with isoflurane delays the onset of hypothermia in rats.

General anesthesia causes hypothermia by impairing normal thermoregulatory mechanisms. When using inhalational anesthetic agents, Redistribution of warm blood from the core to the periphery is the primary mechanism in the development of hypothermia and begins following induction of anesthesia. Raising skin temperature before anesthesia reduces the temperature gradient between core and periphery, decreasing the transfer of heat. This prospective, crossover study (n = 17 adult male and female SD rats) compared three treatment groups: PW1% (pre-warming to increase core temperature 1% over baseline), PW40 (pre-warming to increase core temperature to 40°C) and NW (no warming). The PW1% group was completed first to ensure tolerance of pre-warming. Treatment order was then randomized and alternated after a washout period. Once target temperature was achieved, anesthesia was induced and maintained with isoflurane in oxygen without further external temperature support. Pre-warming was effective at delaying the onset of hypothermia, with a significant difference between PW1% (12.4 minutes) and PW40 (19.3 minutes, p = 0.0044 (95%CI -12 to -2.2), PW40 and NW (7.1 minutes, p < 0.0001 (95%CI 8.1 to 16.0) and PW1% and NW (p = 0.003, 95%CI 1.8 to 8.7). The rate of heat loss in the pre-warmed groups exceed that of the NW group: PW1% versus NW (p = 0.005, 95%CI 0.004 to 0.027), PW40 versus NW (p < 0.0001, 95%CI 0.014 to 0.036) and PW1% versus PW40 (p = 0.07, 95%CI -0.021 to 0.00066). Pre-warming alone confers a protective effect against hypothermia during volatile anesthesia; however, longer duration procedures would require additional heating support.

Facial expressions of pain in cats: the development and validation of a Feline Grimace Scale.

Grimace scales have been used for pain assessment in different species. This study aimed to develop and validate the Feline Grimace Scale (FGS) to detect naturally-occurring acute pain. Thirty-five client-owned and twenty control cats were video-recorded undisturbed in their cages in a prospective, case-control study. Painful cats received analgesic treatment and videos were repeated one hour later. Five action units (AU) were identified: ear position, orbital tightening, muzzle tension, whiskers change and head position. Four observers independently scored (0-2 for each AU) 110 images of control and painful cats. The FGS scores were higher in painful than in control cats; a very strong correlation with another validated instrument for pain assessment in cats was observed (rho = 0.86, p < 0.001) as well as good overall inter-rater reliability [ICC = 0.89 (95% CI: 0.85-0.92)], excellent intra-rater reliability (ICC > 0.91), and excellent internal consistency (Cronbach's alpha = 0.89). The FGS detected response to analgesic treatment (scores after analgesia were lower than before) and a cut-off score was determined (total pain score > 0.39 out of 1.0). The FGS is a valid and reliable tool for acute pain assessment in cats.

Comparing the Rat Grimace Scale and a composite behaviour score in rats.

There is a growing interest in the use of voluntarily displayed ongoing behaviours in laboratory animals to assess the pain experience. In rats, two behavioural pain scales, the Rat Grimace Scale (RGS, a facial expression scale) and a composite behaviour score (CBS, a behavioural ethogram reliant on postural changes), are both promising pain assessment methods. Both scales have been used to assess pain in a laparotomy model, however, they have never been compared directly and the knowledge of how different analgesics may affect these two scales is limited. This study aimed to provide a comparison to discriminate the temporal and analgesic response in a laparotomy model. Female Wistar (n = 26) and Sprague Dawley rats (n = 26) were block randomized to receive saline, meloxicam (2 mg/kg) or buprenorphine (0.05 mg/kg) 30 minutes before laparotomy. Rats were video-recorded before surgery (BL) and at 30, 150, 270, and 390 minutes post-operatively. Videos were assessed according to both scales by a trained, blinded observer. Both CBS and RGS scores increased significantly at all post surgical timepoints in the saline group. Both buprenorphine and meloxicam reduced CBS scores to baseline levels following laparotomy; however, RGS scores were only reduced following buprenorphine. RGS scores in the meloxicam group remained similar to scores of the saline group. These findings suggest that the CBS and RGS differ in their sensitivity to discriminating analgesic effects.

Performance of behavioral assays: the Rat Grimace Scale, burrowing activity and a composite behavior score to identify visceral pain in an acute and chronic colitis model.

INTRODUCTION: The Rat Grimace Scale (RGS), a facial expression scale, quantifies the affective component of pain in rats. The RGS was developed to identify acute and inflammatory pain, and applicability in acute and chronic visceral pain is unknown. The dextran sulfate sodium (DSS) colitis model is commonly used in rats, but pain is rarely assessed, instead, disease progression is monitored with the Disease Activity Index (DAI; assessing fecal blood, stool consistency, and weight loss). OBJECTIVES: The aim of this study was to assess whether the RGS and 2 additional behavioral tools (composite behavior score [CBS] and burrowing) could identify pain in an acute and chronic DSS colitis model. METHODS: Male and female Sprague-Dawley rats were block randomized to (1) acute colitis (4 days DSS in drinking water); (2) chronic colitis (4 days DSS, 7 days water, and 3 days DSS); or (3) control (14 days water). Disease Activity Index, RGS, CBS, and burrowing assessments were performed daily. RESULTS: Rat Grimace Scale scores increased as DAI scores increased during both acute and chronic phases. Burrowing only decreased during the acute phase. By contrast, CBS scores did not increase significantly during either colitis phase. CONCLUSIONS: These data show that the RGS and burrowing did not decrease in a sustained manner during chronic phase visceral pain, and that variables assessed in the DAI are indicative of pain. This suggests that the RGS can be applied to a wider range of pain types and chronicity than originally suggested. These findings increase the application of the RGS as a pain scale and welfare improvement tool.