Monteiro Beatriz P, Klinck Mary P, Moreau Maxim, Guillot Martin, Steagall Paulo V M, Pelletier Jean-Pierre, Martel-Pelletier Johanne, Gauvin Dominique, Del Castillo Jérôme R E, Troncy Eric
GREPAQ (Animal Pharmacology Research Group of Quebec), Faculty of Veterinary Medicine-Université de Montréal, Saint-Hyacinthe, QC, Canada.
Osteoarthritis Research Unit, Research Center of the University of Montreal Hospital Centre, Montreal, QC, Canada.
PLoS One. 2017 Apr 12;12(4):e0175565. doi: 10.1371/journal.pone.0175565. eCollection 2017.
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.
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%.
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.
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.
本研究旨在采用前瞻性、随机、双盲、安慰剂对照、交叉设计，（1）比较正常猫和骨关节炎猫的结局评估指标，（2）评估曲马多对猫骨关节炎（OA）的镇痛效果。
20只猫在进行临床检查、血液检查和全身X光片检查后被纳入研究。在第1阶段，结局评估旨在区分正常猫（n = 5；即无任何OA的影像学和临床体征）和OA猫（n = 15）。在第2阶段，OA猫每天口服两次安慰剂（PG：玉米淀粉15毫克）或曲马多（TG：3毫克/千克），持续19天，两次治疗之间有3个月的洗脱期。在基线时对正常猫和OA猫进行评估，评估内容包括：1）楼梯运动后的垂直峰值力（PVF）；2）遥测夜间运动活动（NMA）；3）对机械性时间总和的反应（RMTS）。治疗后，对OA猫重复进行PVF、NMA和RMTS评估。采用混合模型方法分析数据，α阈值为5%。
第1阶段：1）正常猫的PVF（体重百分比；均值±标准差）（59±10.5）高于OA猫（50.6±5.7）（p = 0.005）；2）两组之间的NMA（无单位）无差异；3）正常猫的RMTS（刺激次数；中位数（范围））[29.5（23.5 - 30）]高于OA猫[14（8.5 - 28）]（p < 0.0001）。第2阶段：PVF、NMA和RMTS均呈现出治疗效果（分别为p = 0.024、p = 0.008和p = 0.018）。未观察到具有临床意义的不良反应。
诸如动力学（PVF）和中枢敏化评估（RMTS）等结局评估指标可区分OA状态。通过NMA测量的运动能力不能区分OA状态，然而在接受曲马多治疗的OA猫中其有所增加。通过RMTS量化的伤害性超敏反应在OA猫中很明显，并且对曲马多治疗有反应。
