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目的研究一种新型N-型电压敏感性钙通道拮抗剂虎纹蜘蛛毒素-I(HWAP-I)经蛛网膜下腔用药对福尔马林诱导的大鼠急性炎性内脏疼痛的抑制作用。方法福尔马林快速注入SD大鼠乙状结肠壁粘膜下层作为疼痛模型,以数种可评估的反映内脏疼痛的固定性行为作为疼痛评分指标(疼痛分数)。此前30min经留置的导管注射各待测试剂于蛛网膜下腔内,以观察其对该模型疼痛行为的作用。结果以生理盐水阴性对照组和美国同类镇痛新药SNX-111(0.2,0.5和0.75μg/kg·b.w.)和盐酸吗啡(0.05,0.1和0.2μg/kg·b.w.)两个阳性对照组比较,HWAP-I(0.1~1.0μg/kg·b.w.)均能以剂量依赖方式明显抑制福尔马林结肠壁粘膜下注射所诱导的大鼠急性伤害性行为反应。HWAP-I和SNX-111在0.2μg/kg·b.w.时即有稳定和明显的疼痛抑制作用。虽然在同等剂量时SNX-111镇痛效果略大于HWAP-I,但在≥0.5μg/kg·b.w.的较高剂量时SNX-111会引起大鼠产生明显的运动能力障碍,而HWAP-I在此剂量范围内则未见明显的这类毒副作用。盐酸吗啡镇痛作用起效快于HWAP-I和SNX-111,但维持时间较后二者短。结论作为一种新型的多肽类N-型电压敏感性钙通道拮抗剂,HWAP-I和其类似物SNX-111经蛛网膜下腔用药后,对结肠壁粘膜下注射福尔马林引起的大鼠急性炎性内脏疼痛具有和盐酸吗?
Objective To study the inhibitory effect of a new type of N-type voltage-sensitive calcium channel antagonist tiger spider toxin-I (HWAP-I) administered subarachnoid on formalin-induced acute inflammatory visceral pain in rats. Methods Formalin was rapidly injected into the submucosa of the sigmoid colon wall of SD rats as a pain model. Several assessable fixed behaviors reflecting visceral pain were used as pain indicators (pain score). Prior to the 30min catheter indwelling catheter injection of each test agent in the subarachnoid cavity in order to observe its role in the pain behavior of the model. Results Compared with the two positive control groups, NSX negative control group and SNX-111 (0.2, 0.5 and 0.75 μg / kg · bw) and morphine hydrochloride (0.05, 0.1 and 0.2 μg / kg · bw) HWAP-I (0.1 ~ 1.0μg / kg · bw) could significantly inhibit the acute nociceptive response induced by submucosal injection of formalin in the colon wall in a dose-dependent manner. HWAP-I and SNX-111 showed stable and obvious pain inhibition at 0.2μg / kg · b.w. Although the analgesic effect of SNX-111 was slightly greater than that of HWAP-I at the same dose, SNX-111 caused significant motor deficits in rats at higher doses of> 0.5 μg / kg · bw, whereas HWAP-I This dose range is no obvious such side effects. Analgesic effect of morphine hydrochloride is faster than that of HWAP-I and SNX-111, but the maintenance time is shorter than the latter. Conclusion As a new type of peptide N-type voltage-sensitive calcium channel antagonist, HWAP-I and its analogs SNX-111 after subarachnoid administration to the colon wall submucosal injection of formalin-induced large Acute inflammatory visceral pain in mice with hydrochloric acid?