BackgroundThe aim of this study was to describe the joint pharmacokinetic-pharmacodynamic model and evaluate thermal antinociception of a high-concentration formulation of buprenorphine (Simbadol™) in cats.MethodsSix healthy cats (4.9 ± 0.7 kg) were included in a prospective, randomized, blinded, crossover study. Simbadol™ (1.8 mg mL-1) was administered by the subcutaneous (SC; 0.24 mg kg-1), intravenous (IV; 0.12 mg kg-1) or buccal (OTM; 0.12 mg kg-1) route of administration and thermal thresholds (TT) were compared with a saline group (SAL). Thermal threshold testing and blood sampling were performed at predetermined time points up to 72 hours including a placebo group. Plasma buprenorphine and norbuprenorphine concentrations were measured using liquid chromatography mass spectrometry. A bespoke bicompartmental pharmacokinetic model simultaneously fitted data from two analytes/three routes of administration. Temporal changes in TT were analyzed using one-way ANOVA followed by Dunnett’s test and treatment comparisons using two-way ANOVA with Bonferroni’s correction (P < 0.05).ResultsThermal thresholds were significantly increased after SC, IV and OTM from 1–24 hours (except 2 hours), 0.5–8 hours (except 6 hours), and 1–8 hours (except 6 hours), respectively, when compared with baseline. Thermal thresholds were significantly increased after SC (1–30 hours), IV (1–8 hours) and OTM (1–12 hours) when compared with SAL, but not different among buprenorphine-treated cats. The absolute buprenorphine clearance was 0.98 L kg-1 hour-1, volume of distribution at steady state was 7.9 L kg-1 and the elimination-half-life was 12.3 hours. Bioavailability for SC and OTM was 94% and 24%, respectively. Subcutaneous absorption was biphasic. An initial peak (0.08 hours) was followed by a slow (half-life 11.2 hours) and progressive (peak acceleration at 2.8 hours) uptake.ConclusionThe SC administration of Simbadol™ was characterized by prolonged absorption half-life and sustained plasma concentrations yielding long-lasting antinociception (≥ 24 hours) when compared with the IV and OTM routes.

Background The Feline Grimace Scale (FGS) is a facial expression-based scoring system for acute pain assessment in cats with reported validity using image assessment. The aims of this study were to investigate the clinical applicability of the FGS in real-time when compared with image assessment, and to evaluate the influence of sedation and surgery on FGS scores in cats. Methods Sixty-five female cats (age: 1.37 ± 0.9 years and body weight: 2.85 ± 0.76 kg) were included in a prospective, randomized, clinical trial. Cats were sedated with intramuscular acepromazine and buprenorphine. Following induction with propofol, anesthesia was maintained with isoflurane and cats underwent ovariohysterectomy (OVH). Pain was evaluated at baseline, 15 min after sedation, and at 0.5, 1, 2, 3, 4, 6, 8, 12 and 24 h after extubation using the FGS in real-time (FGS-RT). Cats were video-recorded simultaneously at baseline, 15 min after sedation, and at 2, 6, 12, and 24 h after extubation for subsequent image assessment (FGS-IMG), which was performed six months later by the same observer. The agreement between FGS-RT and FGS-IMG scores was calculated using the Bland & Altman method for repeated measures. The effects of sedation (baseline versus 15 min) and OVH (baseline versus 24 h) were assessed using linear mixed models. Responsiveness to the administration of rescue analgesia (FGS scores before versus one hour after) was assessed using paired t-tests. Results Minimal bias (−0.057) and narrow limits of agreement (−0.351 to 0.237) were observed between the FGS-IMG and FGS-RT. Scores at baseline (FGS-RT: 0.16 ± 0.13 and FGS-IMG: 0.14 ± 0.13) were not different after sedation (FGS-RT: 0.2 ± 0.15, p = 0.39 and FGS-IMG: 0.16 ± 0.15, p = 0.99) nor at 24 h after extubation (FGS-RT: 0.16 ± 0.12, p = 0.99 and FGS-IMG: 0.12 ± 0.12, p = 0.96). Thirteen cats required rescue analgesia; their FGS scores were lower one hour after analgesic administration (FGS-RT: 0.21 ± 0.18 and FGS-IMG: 0.18 ± 0.17) than before (FGS-RT: 0.47 ± 0.24, p = 0.0005 and FGS-IMG: 0.45 ± 0.19, p = 0.015). Conclusions Real-time assessment slightly overestimates image scoring; however, with minimal clinical impact. Sedation with acepromazine-buprenorphine and ovariohysterectomy using a balanced anesthetic protocol did not influence the FGS scores. Responsiveness to analgesic administration was observed with both the FGS-RT and FGS-IMG.

This study aimed to evaluate pain scores, analgesic requirements, food intake and serum inflammatory cytokines in cats before and after clinically recommended dental treatment. Twenty-four cats were included in a prospective, blinded clinical trial. Cats were equally divided into minimal (minimal dental treatment) or severe (multiple dental extractions) oral disease groups. They were admitted (day 0) and underwent oral examination/radiographs/treatment under general anesthesia (day 1; acepromazine-hydromorphone-propofol-isoflurane-meloxicam-local anesthetic blocks). Serum inflammatory cytokines were measured on days 0 and 6. Pain was scored using the Glasgow composite measure pain scale-feline (CMPS-F). Rescue analgesia was administered with hydromorphone if CMPS-F ≥ 5/20. Dry and soft food intake (%) during 3 minutes and 2 hours, and daily soft food were calculated. The Cochran-Mantel-Haenszel and Chi-square tests, Spearman’s rank correlation and linear mixed models were used for statistical analysis (alpha = 0.05). Pain scores were significantly increased in cats with severe disease when compared with baseline (up to day 4) and minimal disease (all postoperative time points). Prevalence of rescue analgesia was significantly higher in severe (91.7%) than minimal disease (0%); analgesics were required up to day 3. Pain scores and frequency of rescue analgesia were significantly correlated with the number of tooth extractions, gingival and calculus index. Prevalence of rescue analgesia was significantly correlated with the number of missing teeth, teeth extractions and gingival index. Dry and soft food intake during 3 minutes, and dry food intake during 2 hours were significantly lower in the severe than minimal disease group throughout the study. Some cytokines differed between groups between day 0 and day 6 and were associated with the presence of tooth resorption and number of missing tooth and tooth fractures. Long-term analgesia is required after dental extractions in cats with severe oral disease. This condition reduces food intake and influences serum inflammatory cytokines.

This study aimed to evaluate the inter-rater reliability of the Feline Grimace Scale (FGS) in cats undergoing dental extractions and the effects of the caregiver's presence on the FGS scores. Twenty-four cats (6 ± 3.3 years old; 4.9 ± 1.7 kg) undergoing oral treatment were included in a prospective, blinded, randomized, clinical study. They underwent treatment under general anesthesia (acepromazine-hydromorphone-propofol-isoflurane-meloxicam-local anesthetic blocks) at day 1 and were discharged at day 6. Images of cat faces were captured from video recordings with or without the caregiver's presence at 6 h postoperatively (day 1), day 6, and before and after rescue analgesia. Images were randomized and independently evaluated by four raters using the FGS [five action units (AU): ear position, orbital tightening, muzzle tension, whiskers change, and head position; score 0-2 for each]. Inter-rater reliability and the effects of the caregiver's presence were analyzed with intraclass correlation coefficient [single measures (95% confidence interval)] and the Wilcoxon signed-rank test, respectively (p < 0.05). A total of 91 images were scored. Total FGS scores showed good inter-rater reliability [0.84 (0.77-0.89)]. Reliability for each AU was: ears [0.68 (0.55-0.78)], orbital tightening [0.76 (0.65-0.84)], muzzle [0.56 (0.43-0.69)], whiskers [0.64 (0.50-0.76)], and head position [0.74 (0.63-0.82)]. The FGS scores were not different with [0.075 (0-0.325)] or without [0.088 (0-0.525)] the caregivers' presence (p = 0.12). The FGS is a reliable tool for pain assessment in cats undergoing dental extractions. The caregiver's presence did not affect FGS scores.