Abbott Frances V, Franklin Keith B J, Westbrook Frederick R
Department of Psychiatry and School of Nursing, McGill University, Montreal, PQ H3A 1A1, Canada Department of Psychology, McGill University, Montreal, PQ H3A 1A1, Canada School of Psychology, University of New South Wales, Sydney, NSW 2033, Australia.
Pain. 1995 Jan;60(1):91-102. doi: 10.1016/0304-3959(94)00095-V.
The formalin test is increasingly used as a model of injury-produced pain but there is no generally accepted method of pain rating. To examine the properties of various pain rating methods we established dose-response relations for formalin injected in the plantar surface of one hind paw, and the analgesic effects of morphine and amphetamine using the most frequently reported behavioural measures of pain (favouring, lifting, licking and flinching/shaking of the injured paw) and combinations of these. Licking, elevation and favouring of the injected paw showed a biphasic response at all formalin doses. Flinching varied in form across the time course of formalin, and the biphasic nature of the behaviour was not as apparent. In untreated rats all these behaviours were infrequent. Flinching and favouring were increased after injection of local anaesthetic into the paw but remained negligible relative to the effect of formalin. Grooming other than that directed to the injected paw was elevated in a dose-dependent manner by formalin. Intercorrelations between the behaviours were different for the initial response and the second phase. Correlational analysis indicated that no single behavioural measure was a strong predictor of formalin, morphine and amphetamine dose. A simple sum of time spent licking plus elevating the paw, or the weighted pain score of Dubuisson and Dennis (1977), were superior to any single measure (r ranging from 0.75 to 0.86). Addition of flinching and favouring to the combined pain score using multiple regression did not increase variance explained. Depending on the measure used, a sedative dose of pentobarbital produced apparent analgesia, hyperalgesia or no effect. The interphase depression of pain, as well as the analgesic effects of morphine and amphetamine, were all associated with increased motor activation. Power analysis indicated that using a moderate dose of formalin and a combined pain score gave the greatest power to detect differences in pain. It was also found that pain scores increase with ambient temperature and that rat strains may differ in formalin pain sensitivity.
福尔马林试验越来越多地被用作损伤性疼痛的模型，但目前尚无普遍接受的疼痛评分方法。为了研究各种疼痛评分方法的特性，我们建立了在一只后爪足底注射福尔马林的剂量反应关系，以及使用最常报告的疼痛行为指标（受伤爪子的偏好、抬起、舔舐和退缩/抖动）及其组合来评估吗啡和苯丙胺的镇痛效果。在所有福尔马林剂量下，注射爪子的舔舐、抬高和偏好均呈现双相反应。在福尔马林作用的整个时间过程中，退缩的形式有所不同，且该行为的双相性质并不明显。在未处理的大鼠中，所有这些行为都很少见。向爪子注射局部麻醉剂后，退缩和偏好有所增加，但相对于福尔马林的作用而言，仍可忽略不计。福尔马林以剂量依赖性方式增加了除针对注射爪子之外的梳理行为。行为之间的相互关系在初始反应和第二阶段有所不同。相关性分析表明，没有单一的行为指标能强有力地预测福尔马林、吗啡和苯丙胺的剂量。舔舐加抬起爪子的简单时间总和，或杜布瓦松和丹尼斯（1977年）的加权疼痛评分，优于任何单一指标（r值范围为0.75至0.86）。使用多元回归将退缩和偏好添加到综合疼痛评分中，并没有增加可解释的方差。根据所使用的指标，镇静剂量的戊巴比妥可产生明显的镇痛、痛觉过敏或无作用。疼痛的中间期抑制以及吗啡和苯丙胺的镇痛作用均与运动激活增加有关。功效分析表明，使用中等剂量的福尔马林和综合疼痛评分能最有效地检测疼痛差异。还发现疼痛评分随环境温度升高而增加，并且不同品系的大鼠对福尔马林疼痛的敏感性可能存在差异。
