Search

This study aimed to characterize bone cancer pain (quantitative sensory testing (QST), stance asymmetry index, actimetry, scores of pain and quality of life (QoL)) in dogs with appendicular osteosarcoma (OSA), and to evaluate a stepwise palliative analgesic treatment. The pain profile of thirteen client-owned dogs with OSA was compared with seven healthy dogs. Dogs with OSA were then enrolled in a prospective, open-label, clinical trial. Outcome measures included: primary and secondary mechanical thresholds (MT), conditioned pain modulation (CPM), stance asymmetry index, actimetry (most and least active periods), visual analog scales and QoL. After baseline assessments, stepwise treatment comprised orally administered cimicoxib (2 mg/kg q 24h), amitriptyline (1–1.5 mg/kg q 24h) and gabapentin (10 mg/kg q 8h); re-evaluations were performed after 14 (D14), 21 (D21) and 28 (D28) days, respectively. Statistics used mixed linear models (α = 5%; one-sided). Centralized nociceptive sensitivity (primary and secondary MT, and dynamic allodynia) was recorded in OSA dogs. Healthy dogs had responsive CPM, but CPM was deficient in OSA dogs. Construct validity was observed for the QST protocol. Asymmetry index was significantly present in OSA dogs. The CPM improved significantly at D14. When compared with baseline (log mean ± SD: 4.1 ± 0.04), most active actimetry significantly improved at D14 (4.3 ± 0.04), D21 and D28 (4.2 ± 0.04 for both). When compared with baseline, least active actimetry significantly decreased after treatment at all time-points indicating improvement in night-time restlessness. No other significant treatment effect was observed. Except for tactile threshold and actimetry, all outcomes worsened when gabapentin was added to cimicoxib-amitriptyline. Dogs with bone cancer are affected by widespread somatosensory sensitivity characterized by peripheral and central sensitization and have a deficient inhibitory system. This severe pain is mostly refractory to palliative analgesic treatment, and the latter was only detected by specific and sensitive outcomes. [ABSTRACT FROM AUTHOR]

Background: The 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. Methods: Six 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). Results: Thermal 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. Conclusion: The 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. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to (1) compare outcome assessments in normal and osteoarthritic cats and (2) evaluate the analgesic efficacy of tramadol in feline osteoarthritis (OA), in a prospective, randomised, blinded, placebo-controlled, crossover design. Methods: Twenty cats were included after clinical examination, blood work and full body radiographs were performed. In Phase 1, outcome assessments aimed to differentiate normal (n = 5; i.e. exempt of any radiographic and clinical sign of OA) from OA (n = 15) cats. In Phase 2, OA cats were treated twice daily with a placebo (PG: cornstarch 15 mg) or tramadol (TG: 3 mg/kg) orally for 19 days, with a 3-month washout period between treatments. Evaluations were performed in normal and OA cats at baseline and consisted of: 1) peak vertical force (PVF) after staircase exercise; 2) telemetered night-time motor activity (NMA); and 3) response to mechanical temporal summation (RMTS). After treatment, PVF, NMA and RMTS evaluations were repeated in OA cats. Data were analysed with mixed model methods with an alpha-threshold of 5%. Results: Phase 1: 1) PVF (% of body weight; mean ± SD) was higher in normal (59 ± 10.5) than in OA cats (50.6 ± 5.7) (p = 0.005); 2) NMA (no unit) was not different between groups; 3) RMTS (number of stimuli; median (range)) was higher in normal [29.5 (23.5–30)] than in OA cats [14 (8.5–28)] (p < 0.0001). Phase 2: PVF, NMA and RMTS presented a treatment effect (p = 0.024, p = 0.008 and p = 0.018, respectively). No clinically important adverse-effects were observed. Conclusion: Outcome assessments such as kinetics (PVF) and evaluation of central sensitisation (RMTS) are discriminant of OA status. Mobility measured by NMA was not discriminant of OA status, however it increased in OA cats with tramadol treatment. Nociceptive hypersensitivity quantified by RMTS was evident in OA cats and was responsive to tramadol treatment. [ABSTRACT FROM AUTHOR]