Purpose Compare non-parametric permutation method using intr-meal rate as endpoint to existing ANOVA method that uses average daily meal duration as an endpoint for detection of chronic pain in Sprague-Dawley rats. Methods Nociception following bilateral temporomandibular joint (TMJ) injection of high-dose of Complete Freunds Adjuvant (CFA, 250 μg/50 μL per side) could be detected in young adult male Sprague-Dawley rats using average daily meal durations as a measure of nociception for up to 19 days (Kramer, Kerins, Schneiderman, & Bellinger, 2010) using ANOVA and multiple comparisons range tests. In this study, we reanalyzed the data using a non-parametric permutation procedure based on absolute differences between intra-meal feeding rate curves. In addition, to that experiment, we injected bilaterally the TMJ of naive rats with either a low-dose CFA (15 μg/50 μL per side, n=6) or saline (50 μL of 0.9%, n=4) and monitored the animals for 7 days. Results The permutation test of the intra-meal feeding rate detected the presence of nociception in the high-dose CFA treatment group for up to 40 days or twice as long as when using ANOVA on average daily meal durations. The permutation method also detected the low-dose CFA induced nociception with ten-times lower p-values and for several days longer than ANOVA of changes in meal durations. CFA-induced injury resulted in even reduction of intra-meal feeding rate and lengthening of the meals in both high- and low-dose CFA-injected animals. The rate analysis also showed when the rats first started a meal they were experiencing the same level of nociception as at the end of the meal. This demonstrated that intra-meal chewing itself did not alter the level of nociception. Conclusions These results suggest that permutation tests based on differences in intra-meal feeding rates can be used as a sensitive test to determine and study the temporal patterns of TMJ nociception.

中文翻译：

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基于距离的餐间差异排列作为大鼠颞下颌关节痛觉的敏感测试

目的将使用餐间率作为终点的非参数排列方法与使用平均每日进餐持续时间作为检测 Sprague-Dawley 大鼠慢性疼痛终点的现有方差分析方法进行比较。方法 使用平均每日进餐时间作为伤害感受的衡量标准，可以在年轻的成年雄性 Sprague-Dawley 大鼠中检测到双侧颞下颌关节 (TMJ) 注射高剂量完全弗氏佐剂（CFA，每侧 250 μg/50 μL）后的伤害感受使用方差分析和多重比较范围检验最多 19 天（Kramer、Kerins、Schneiderman 和 Bellinger，2010）。在这项研究中，我们使用基于餐内喂食率曲线之间的绝对差异的非参数排列程序重新分析了数据。此外，对于那个实验，我们用低剂量 CFA（每侧 15 μg/50 μL，n=6）或生理盐水（50 μL，0.9%，n=4）双侧注射幼稚大鼠的 TMJ，并监测动物 7 天。结果 餐内喂养率的排列测试检测到高剂量 CFA 治疗组中存在伤害感受长达 40 天或使用方差分析时平均每日进餐持续时间的两倍。置换方法还检测到低剂量 CFA 诱导的伤害感受，其 p 值低 10 倍，且持续时间比用餐持续时间变化的方差分析长几天。CFA 诱导的损伤甚至导致高剂量和低剂量 CFA 注射动物的餐内喂食率降低和进餐时间延长。速率分析还显示，当大鼠第一次开始进餐时，它们所经历的伤害感受水平与进餐结束时相同。这表明餐内咀嚼本身并没有改变伤害感受的水平。结论 这些结果表明，基于餐内喂养率差异的排列测试可用作确定和研究 TMJ 伤害感受的时间模式的敏感测试。