Bristol Veterinary School, University of Bristol, Bristol, United Kingdom.
Arthritis Research UK Pain Centre, and Division of Animal Sciences, School of Biosciences, University of Nottingham, Loughborough, United Kingdom.
Pain. 2018 Nov;159(11):2318-2330. doi: 10.1097/j.pain.0000000000001336.
In man, central sensitisation (CS) contributes to the pain of osteoarthritis (OA). Dogs with spontaneous OA may also exhibit CS. Electrophysiological reflex measurements are more objective than behavioural assessments and can be used to evaluate CS in preclinical and clinical studies. It was hypothesised that dogs suffering from OA would exhibit electrophysiological characteristics indicative of CS, associated with reduced diffuse noxious inhibitory controls (DNICs). One hundred and seventeen client-owned dogs were recruited to the study. Hind limb nociceptive withdrawal reflex thresholds, stimulus response, and temporal summation characteristics were recorded, during alfaxalone anaesthesia, from 46 OA dogs, 29 OA dogs receiving nonsteroidal anti-inflammatory drugs (OANSAIDs), and 27 breed- and weight-matched control dogs. Efficacy of DNIC was evaluated in 12 control and 11 of the OA dogs, by application of a mechanical conditioning stimulus to the contralateral forelimb. Nociceptive withdrawal reflex thresholds were higher in OA compared with control dogs (P = 0.02). Stimulus response characteristics demonstrated an augmented response in OANSAID dogs compared with OA (P < 0.001) and control (P < 0.001) dogs. Temporal summation demonstrated exaggerated C-fibre-mediated responses in both OA (P < 0.001) and OANSAID (P = 0.005) groups, compared with control animals. Conditioning stimulus application resulted in inhibition of test reflex responses in both OA and control animals (P < 0.001); control animals demonstrated greater inhibition compared with OA (P = 0.0499). These data provide evidence of neurophysiological changes consistent with CS in dogs with spontaneous OA and demonstrate that canine OA is associated with reduced DNIC.
在人类中,中枢敏化(CS)导致骨关节炎(OA)的疼痛。患有自发性 OA 的狗也可能表现出 CS。电生理反射测量比行为评估更客观,可用于评估临床前和临床研究中的 CS。研究假设患有 OA 的狗会表现出 CS 的电生理特征,与降低的弥散性伤害性抑制控制(DNIC)相关。招募了 117 只患 OA 的犬进行研究。在 alfaxalone 麻醉下,记录了 46 只 OA 犬、29 只接受非甾体抗炎药(OANSAID)的 OA 犬和 27 只品种和体重匹配的对照犬的后肢伤害性撤回反射阈值、刺激反应和时间总和特征。通过对健侧前肢施加机械条件刺激,评估了 12 只对照犬和 11 只 OA 犬的 DNIC 效能。OA 犬的伤害性撤回反射阈值高于对照犬(P = 0.02)。刺激反应特征表明,与 OA 犬(P < 0.001)和对照犬(P < 0.001)相比,OANSAID 犬的反应增强。时间总和显示,OA 犬(P < 0.001)和 OANSAID 犬(P = 0.005)组的 C 纤维介导反应均过度放大,与对照动物相比。在 OA 和对照动物中,施加条件刺激都会抑制测试反射反应(P < 0.001);对照动物的抑制作用大于 OA 动物(P = 0.0499)。这些数据提供了支持自发性 OA 犬 CS 的神经生理学变化的证据,并表明犬 OA 与降低的 DNIC 相关。