Development of objective criteria of pain in animals.

首先，在狗身上评估了有害刺激和神经激素反应之间的关系。记录大手术期间心率、血压、血浆ACTH和皮质醇水平的变化。除了皮肤切口外，许多狗的心率和血压在大手术操作期间或之后没有明显变化。相反，在大多数犬中，血浆ACTH和皮质醇水平根据手术操作的效力程度而变化。皮质醇被认为比ACTH更有价值，因为它的个体差异较小，易于测量方案。此外，使用吗啡或芬太尼等强效镇痛药可显著抑制手术操作引起的血浆皮质醇水平升高。其次，非甾体抗炎药（NSAID）与阿片类药物在手术期间和手术后的皮质醇水平进行比较。先发制人给予非甾体抗炎药抑制了手术操作引起的血浆皮质醇水平的升高，并将其维持在与手术期间和术后给予阿片类药物的狗相似的水平。此外，两组患者术后疼痛评分的变化与血浆皮质醇水平的变化具有良好的相关性。最后，用皮质醇水平评价大剂量阿片类药物加或不加辅助药物对毒性刺激引起的神经激素反应的影响。大剂量芬太尼联合氯胺酮和利多卡因在手术过程中发挥了几乎完全的抗痛觉作用。综上所述，血浆皮质醇水平是判断犬疼痛的客观、有价值的标准。

First, the relationship between noxious stimulus and neurohormonal responses was evaluated in dogs. The changes in heart rate, blood pressure and plasma ACTH and cortisol levels were recorded during major surgeries. Heart rate and blood pressure did not change significantly during or after major surgical manipulation except for skin incision in many dogs. On the contrary, the plasma ACTH and cortisol levels changed in accordance to the degree of potency of surgical manipulation in most dogs. Cortisol was thought to be more valuable than ACTH because of its less individual differences and easy measurement protocol. In addition, the increase in plasma cortisol level induced by surgical manipulation was significantly suppressed by use of potent analgesics such as morphine or fentanyl.Second, antinociceptive effect of a non steroidal anti-inflammatory drug (NSAID) was compared with that of opioids by use of cortisol levels during and after surgery. Preemptive administration of NSAID suppressed the increase in plasma cortisol level caused by surgical manipulation and maintained it at similar level to that in dogs given opioids during and after operation. In addition, the changes in post-operative pain score determined by visual analog scale (VAS) were well correlated with the changes in plasma cortisol levels in both groups.Finally, the effect of high dose of opioid with or without adjunctive drugs on neurohormonal response caused by noxious stimulus was evaluated by use of cortisol level. High dose of fentanyl with ketamine and lidocaine exerted almost complete antinociceptive effects during surgery.In conclusion, plasma cortisol level is a valuable and objective criteria of pain in dogs.