Nakama-Kitamura Mototaka
Department of Psychology, Kwansei Gakuin University, Nishinomiya, Japan.
Life Sci. 2002 Dec 20;72(4-5):531-40. doi: 10.1016/s0024-3205(02)02248-8.
Tolerance to morphine analgesia was determined by daily exposing rats either to the same box or different boxes during repeated administration of formalin (2.5%, 0.4 mL/body, sc) and morphine (5 mg/kg, sc). The analgesic effect was determined daily for four consecutive days by exposing rats to either the same box or different boxes, and the process of tolerance development was assessed by a hot plate test (52.5 degrees C). The rats were divided into four groups: one group received formalin and morphine in the same context (Group FM-Same), one group in the different context (Group FM-Diff), one group received saline and morphine in the same context (Group SM-Same), two groups received formalin in the same or different contexts (Groups FS-Same or FS-Diff), and one group received saline in the same context (Group SS-Same). The response latency of Group SM-Same was decreased from Day 2 to a level similar to that of Group SS-Same on Day 4, while that of FM-Same decreased more slowly. The latency of Group FM-Diff maintained the level of Day 2 until Day 4, being significantly longer than that of FM-Same. In the Extinction Phase, all rats received formalin and saline injections in the same box they had been exposed to on Day 1. On the first day, hyperalgesia was evident in Group SM-Same alone. In the Re-test Phase, the rats underwent a second morphine injection, and showed recovery from tolerance. These results indicate that formalin-induced chronic stress pain reduces tolerance development to morphine, and the mutual influence of pain, counterirritation, between formalin and hot-plate, facilitates the effect of contextual cues by inhibiting an associative learning.
通过在重复给予福尔马林（2.5%，0.4 mL/只，皮下注射）和吗啡（5 mg/kg，皮下注射）期间，每日将大鼠置于相同或不同的盒子中，来测定对吗啡镇痛的耐受性。连续四天每日通过将大鼠置于相同或不同的盒子中测定镇痛效果，并通过热板试验（52.5℃）评估耐受性发展过程。大鼠被分为四组：一组在相同环境中接受福尔马林和吗啡（FM-相同组），一组在不同环境中接受（FM-不同组），一组在相同环境中接受生理盐水和吗啡（SM-相同组），两组在相同或不同环境中接受福尔马林（FS-相同组或FS-不同组），一组在相同环境中接受生理盐水（SS-相同组）。SM-相同组的反应潜伏期从第2天开始下降，到第4天降至与SS-相同组相似的水平，而FM-相同组的下降则较为缓慢。FM-不同组的潜伏期在第4天前一直维持在第2天的水平，显著长于FM-相同组。在消退期，所有大鼠在第1天接触过的相同盒子中接受福尔马林和生理盐水注射。第一天，仅SM-相同组出现明显的痛觉过敏。在重新测试期，大鼠接受第二次吗啡注射，并显示出耐受性恢复。这些结果表明，福尔马林诱导的慢性应激性疼痛会降低对吗啡耐受性的发展，并且福尔马林和热板之间疼痛、对抗刺激的相互影响，通过抑制联想学习促进了情境线索的作用。
