Wang Pei-Fen, Zhang Yu-Qiu, Qiu Zhui-Bai, Zhao Zhi-Qi
Institute of Neurobiology, Fudan University, Shanghai 200433, China.
Sheng Li Xue Bao. 2004 Jun 25;56(3):295-300.
Using the latency of paw withdrawal (PWL) from a noxious thermal stimulus as a measure of hyperalgesia, the effects of i.p. injection of meptazinol and its isomers, 112824 and 112825, on carrageenan-induced thermal hyperalgesia were studied in awaked carrageenan-inflamed rats. Peripheral inflammation was induced by intraplantar (i.pl.) injection of carrageenan (2 mg/100 microl) into one hindpaw in rats. Carrageenan produced marked inflammation (edema and erythema) and thermal hyperalgesia in the injected paws, which peaked at 3 h after injection and showed little change in magnitude for another 3 h. Injection of 0.1 mg/kg meptazinol (i.p.) at 3 h after carrageenan had no effect on the PWLs of either inflamed or non-inflamed hindpaw during the next 100 min (P>0.05, n=8). At the dosage of 1 and 10 mg/kg, meptazinol produced marked anti-nociception and anti-hyperalgesia in non-inflamed and inflamed hindpaw, respectively (P<0.05, n=8-11). The prolonging effect of meptazinol on PWL in inflamed hindpaw was more potent than that in non-inflamed hindpaw. Pre-administration of 1.5 mg/kg naloxone significantly antagonized meptazinol-induced anti-nociception and anti-hyperalgesia. Intraperitoneal injection of an isomer of meptazinol, 112825 (1.5 mg/kg), but not 112824 (1 mg/kg), markedly increased the PWL of the non-inflamed hindpaw. Nevertheless, both the isomers produced similar anti-hyperalgesic effect to that of meptazinol (P<0.05, n=8), which was completely reversed by naloxone (1.5 mg/mg). The results suggest that meptazinol and its isomers have anti-nociceptive and anti-hyperalgesic properties with the former more potent. The effects are mainly mediated by mu opioid receptors. This study provides an important clue for extending clinical utilization of meptazinol and its isomers.
以对有害热刺激的爪部退缩潜伏期（PWL）作为痛觉过敏的指标，在清醒的角叉菜胶致炎大鼠中，研究了腹腔注射美普他酚及其异构体112824和112825对角叉菜胶诱导的热痛觉过敏的影响。通过向大鼠一侧后爪足底注射角叉菜胶（2mg/100μl）诱导外周炎症。角叉菜胶在注射爪部产生明显的炎症（水肿和红斑）和热痛觉过敏，在注射后3小时达到峰值，并且在接下来的3小时内幅度几乎没有变化。在角叉菜胶注射后3小时腹腔注射0.1mg/kg美普他酚，在接下来的100分钟内对发炎或未发炎后爪的PWL均无影响（P>0.05，n = 8）。在1mg/kg和10mg/kg剂量下，美普他酚分别在未发炎和发炎后爪产生明显的镇痛和抗痛觉过敏作用（P<0.05，n = 8 - 11）。美普他酚对发炎后爪PWL的延长作用比未发炎后爪更强。预先给予1.5mg/kg纳洛酮可显著拮抗美普他酚诱导的镇痛和抗痛觉过敏作用。腹腔注射美普他酚的异构体112825（1.5mg/kg），而非112824（1mg/kg），可显著增加未发炎后爪的PWL。然而，两种异构体产生的抗痛觉过敏作用与美普他酚相似（P<0.05，n = 8），且被纳洛酮（1.5mg/kg）完全逆转。结果表明，美普他酚及其异构体具有镇痛和抗痛觉过敏特性，前者作用更强。其作用主要由μ阿片受体介导。本研究为扩大美普他酚及其异构体的临床应用提供了重要线索。
