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目的探讨胍丁胺对神经病理性痛大鼠吗啡镇痛作用及耐受的影响。方法雄性SD 大鼠,体重160-180 g,制备坐骨神经慢性束缚性损伤(CCI)模型,用von Frey丝测定各项实验中给药前及给药后30、60、120、180、240min时机械缩腿阈值(PWT),并根据PWT计算药物最大可能镇痛百分率(PMAP)。1.选取CCI模型大鼠35只,随机分为5组(n=7),分别腹腔注射等体积生理盐水及40、60、80、100mg/kg胍丁胺,测定PWT并确定给药后30min PMAP<40%时胍丁胺的剂量;选取CCI模型大鼠35只,随机分为5组(n=7),分别皮下注射等体积生理盐水及1、2、3、5 mg/kg吗啡,测定PWT并确定给药后30min PMAP<40%时吗啡的剂量;2.选取CCI模型大鼠56只,随机分为8组(n=7),观察胍丁胺与吗啡的相互作用,计算PMAP;3.选取CCI模型大鼠35只,随机分为5组(n=7),诱导吗啡耐受产生,观察不同剂量胍丁胺与吗啡联合应用时PMAP的变化。结果大鼠腹腔注射胍丁胺后30 min PMAP高于注射生理盐水大鼠(P<0.01)。大鼠皮下注射吗啡后30min PMAP高于注射生理盐水大鼠(P<0.01)。与单独给予吗啡和单独给予胍丁胺比较,胍丁胺60mg/kg可使吗啡PMAP升高(P< 0.01),镇痛时间延长(P<0.05)。吗啡耐受实验第6天腹腔注射胍丁胺+皮下注射吗啡大鼠PMAP 高于注射生理盐水吗啡大鼠(P<0.01)。结论胍丁胺对神经病理性痛大鼠具有镇痛作用,且能增强吗啡的镇痛作用,抑制吗啡耐受的形成。
Objective To investigate the effects of agmatine on morphine analgesia and tolerance in neuropathic pain rats. Methods Male Sprague Dawley rats weighing 160-180 g were used to establish chronic constriction injury (CCI) model of sciatic nerve. Before and after administration of von Frey silk, the mechanical Thresholding threshold (PWT) was calculated and the maximum possible analgesia (PMAP) was calculated based on PWT. Thirty-five CCI model rats were randomly divided into 5 groups (n = 7). The rats were injected intraperitoneally with equal volume of normal saline and 40, 60, 80 and 100 mg / kg agmatine respectively. The dose of agmatine at PMAP <40%. Thirty-five CCI model rats were randomly divided into 5 groups (n = 7). The rats were injected subcutaneously with normal saline and morphine with 1, 2, 3 and 5 mg / PWT was determined and the dose of morphine was determined at PMAP <40% at 30min after administration. 56. Fifty-six CCI model rats were randomly divided into 8 groups (n = 7). The interaction between agmatine and morphine was observed and PMAP 35 rats were randomly divided into 5 groups (n = 7) to induce morphine tolerance. The changes of PMAP in different doses of agmatine and morphine were observed. Results The PMAP at 30 min after intraperitoneal injection of agmatine was higher than that of saline injected rats (P <0.01). PMAP was higher at 30 minutes after subcutaneous injection of morphine in rats than in saline rats (P <0.01). Compared with morphine alone and agmatine alone, agmatine 60 mg / kg increased morphine PMAP (P <0.01) and prolonged analgesia (P <0.05). Morphine tolerance test PMAP was higher in morphine-treated rats on the 6th day after intraperitoneal injection of agmatine + morphine than in morphine-injected rats (P <0.01). Conclusion Agmatine has analgesic effect on neuropathic pain rats, and can enhance the analgesic effect of morphine and inhibit the formation of morphine tolerance.