Heilborn Umut, Berge Odd-Geir, Arborelius Lotta, Brodin Ernst
Department of Physiology and Pharmacology, Karolinska Institutet, S-171 77 Stockholm, Sweden.
Brain Res. 2007 Apr 27;1143:143-9. doi: 10.1016/j.brainres.2007.01.054. Epub 2007 Jan 25.
The development of transgenic techniques has accentuated the need for valid disease models in mice. In the present study, we have in female mice characterized adjuvant-induced monoarthritis, an inflammatory model which is commonly used in rats. Freund's complete adjuvant (FCA), 20 microl, was injected into the left knee joint. Pain was inferred from impairment of gait and stance. Two commonly used mouse strains were compared. Outbred NMRI mice showed significant levels of pain behaviour lasting for at least 7 days after injection of FCA while inbred BALB/c mice showed altered behaviour at 3, but not at 5 days. The effects of three commercially available preparations of FCA were compared in NMRI mice. All adjuvants caused highly reproducible spontaneous pain behaviour at 1-3 days with a reduction at 5 days and no significant pain-related behaviour at 10 days. Intraarticular injection of 2% carrageenan performed for comparison, caused pain-related behaviour for less than 24 h. The adjuvant-induced pain behaviour was dose-dependently reduced by 3-30 micromol/kg morphine and 3-30 micromol/kg diclofenac. In conclusion, adjuvant-induced monoarthritis in mice provides a robust model for pharmacological studies of inflammatory pain, but the choice of mouse strain is important for the outcome.
转基因技术的发展凸显了在小鼠中建立有效疾病模型的必要性。在本研究中,我们对雌性小鼠的佐剂诱导性单关节炎进行了特征描述,这是一种常用于大鼠的炎症模型。将20微升弗氏完全佐剂(FCA)注入左膝关节。通过步态和姿势的受损情况推断疼痛。比较了两种常用的小鼠品系。远交系NMRI小鼠在注射FCA后至少持续7天表现出显著水平的疼痛行为,而近交系BALB/c小鼠在第3天表现出行为改变,但在第5天未出现。在NMRI小鼠中比较了三种市售FCA制剂的效果。所有佐剂在1 - 3天引起高度可重复的自发疼痛行为,在第5天有所减轻,在第10天无明显的疼痛相关行为。为作比较,关节内注射2%角叉菜胶引起的疼痛相关行为持续时间不到24小时。佐剂诱导的疼痛行为可被3 - 30微摩尔/千克吗啡和3 - 30微摩尔/千克双氯芬酸剂量依赖性地减轻。总之,小鼠佐剂诱导性单关节炎为炎症性疼痛的药理学研究提供了一个可靠的模型,但小鼠品系的选择对结果很重要。