目的探讨蛋白酶激活受体1激动剂对神经病理性疼痛(NP)大鼠行为学的影响。方法选取SD大鼠40例,采用随机数表法分为对照组、假手术组(Sham组)、坐骨神经慢性结扎损伤(CCI)组和CCI+PAR1组,每组10只。CCI大鼠建模:结扎左结扎坐骨神经中段,假手术组只钝性分离肌肉,使坐骨神经充分暴露而不结扎。分别于术前、术后7 d观察各组大鼠行为学变化,并采用电子vonFrey测痛仪测定各组大鼠缩足反射阈值(MWT)。结果对照组和假手术组大鼠未观察到行为学变化。CCI大鼠术后健康状况均良好,体质量未见明显减轻,毛发光泽性良好,进食饮水习惯未见明显变化。建模术后,大鼠逐渐出现痛敏体征。术后CCI+PAR1组大鼠的自发疼痛行为明显减少。CCI大鼠在术后第1天时左后肢对机械刺激的敏感性增加,机械触压痛阈值下降。CCI组术后第7天左侧后肢机械触压痛阈值为(26.3±4.0) g,与假手术组的(48.1±0.5) g比较下降45.3%,差异有统计学意义(P<0.05);对照组大鼠在各时间点与 sham组及术前相比差异均无统计学意义(P>0.05);CCI+PAR1组与CCI组相比,大鼠术后痛阈值明显增加,术后 7 d左侧后肢机械触压痛阈值为(36.7±5.5) g,比CCI组痛阈提高 39.5%,但与术前痛阈(47.5±1.4) g相比,差异仍有统计学意义(P<0.05)。结论PAR1受体激动剂可减轻NP大鼠左后肢对机械刺激的敏感性,提高机械触压痛阈值。
Objective To investigate the effect of protease-activated receptor 1 (PAR1) agonist on the behaviors of rats with neuropathic pain. Methods According to random number table method, 40 SD rats were randomly divided to four group (each group, n=10): control group, sham group, chronic constrictive injury (CCI) group, and CCI+PAR1 group. CCI model was used to induce neuropathic pain: the left sciatic nerve was visualized and ligated with 4-0 silk;while, the sciatic nerve of sham group was visualized through operation without ligation. All the animals were observed their behavior and mechanical withdrawal threshold (MWT) was measured by electronic von Frey anesthesiometer, before surgery and 7 days after the surgery. Results There was no difference between the control group and sham group on the behaviors after the surgery. CCI rats were all in good health, without any weight loss and changes in their diet. After modeling, the rats gradually developed the signs of hyperalgia. CCI produced rapid-onset and long-lasting thermal hyperalgesia and mechanical allodynia in rats. PAR1 agonist treatment significantly reduced severity of thermal hyperalgesia and mechanical allodynia. Day one after the operation, the mechanical withdrawal threshold of the CCI group was decreased. On day 7, the MWT of CCI group was (26.3±4.0) g, which was 45.3% less than (48.1±0.5) g of the sham group(P<0.05); while the MWT of CCI+PAR1 group was (36.7±5.5) g, which was 39.5% higher than that of the CCI group (P<0.05), however, it was still significantly lower than (47.5±1.4) g of itself before the surgery (P<0.05). Conclusion PAR1 agonist treatment significantly can reduce the severity of thermal hyperalgesia and mechanical allodynia.
Hainan Medical Journal
Protease-activated receptor 1 (PAR1)
Mechanical withdrawal threshold (MWT)