摘要
目的脑干下行纤维释放到脊髓的5-羟色胺(HT)在病理性痛中发挥重要的调控作用,其机制尚不清楚。应用蜜蜂毒(BV)炎性痛大鼠模型,探讨脊髓5-HT是否通过脊髓背角N-甲基-D-天冬氨酸受体NR1亚基和细胞外信号调节蛋白激酶(ERK)的激活发挥调控作用。方法动物随机分为6组:生理盐水对照组(足底注射生理盐水,NS组),BV组(足底注射BV),5, 7-二羟色胺(5, 7-DHT)-BV组(鞘内给予5, 7-DHT后足底注射BV),5, 7-DHT-NS组(鞘内给予5, 7-DHT后足底注射生理盐水),溶剂-NS组(鞘内给予5, 7-DHT溶剂后足底注射生理盐水),溶剂-BV组(鞘内给予5, 7-DHT溶剂后足底注射BV)。大鼠足底注射BV前鞘内连续给予5, 7-DHT预处理4 d,免疫荧光法观察大鼠脊髓NR1亚基、ERK的活化,行为学方法观察痛相关行为学变化。结果溶剂-BV组大鼠注射BV后2 h脊髓背角可见散在的磷酸化(p)-NR1-IR和p-ERK-IR神经元,主要分布于脊髓背角Ⅰ~Ⅱ层,与BV组相似。5, 7-DHT-BV组大鼠脊髓背角浅层p-NR1-IR神经元数目显著高于溶剂-BV组大鼠。鞘内注射5, 7-DHT同样促进了BV诱发的脊髓背角ERK的活化。与溶剂-BV组相比,5, 7-DHT-BV大鼠足底注射BV后出现了严重的痛相关行为:自发缩足反射持续时间从50min增加到120 min,且每5 min自发缩足反射次数也显著增加;热和机械痛敏更加严重。结论在BV炎性刺激下,5-HT可能通过抑制NR1亚基和ERK的激活而发挥部分镇痛作用。
Objective Spinal cord 5-hydroxytryptamine(5-HT)released from descending fibers is believed to exert antinociceptive effects in inflammatory&neuropathic pain circumstances.However,the mechanism is still not clear.NR1 subunit and extracellular signal-regulated protein kinase(ERK)are two key nociception processing elements.It was assumed that spinal cord 5-HT exerts antinociceptive effects through inhibiting NR1 subunit and ERK activation in the dorsal spinal cord following bee venom(BV)peripheral injection.Methods To demonstrate this hypothesis,rats were randomly divided into 6 groups:a normal saline group(intraplantar normal saline injection,NS group),BV group(intraplantar BV injection),5,7-dihydroxytryptamine(5,7-DHT)-BV group(intrathecally 5,7-DHT administration before intraplantar BV injection),5,7-DHT-NS group(intrathecally 5,7-DHT administration before intraplantar NS injection),vehicle-NS group(intrathecally vehicle administration before intraplantar NS injection),and vehicle-BV group(intrathecally vehicle administration before intraplantar BV injection).The rats were intrathecally administrated with 5,7-DHT for 4 days before intraplantar BV injection,and then spinal NR1 subunit and ERK activation as well as pain-related behaviors induced by intraplantar BV injection were detected.Results It was found that scattered phosphorylated(p)-NR1-IR and p-ERK-IR neuronal cells were observed in the dorsal spinal cord at 2 h after BV injection in vehicle pre-treated rats,mainly located in the superficial spinal cord just like the BV group.The number of p-NR1-IR neuronal cells in the superficial spinal cord in the 5,7-DHT pre-treated BV-inflamed rats was significantly higher than that in the vehicle pre-treated BV-inflamed rats.Intrathecally administration of 5,7-DHT also facilitated ERK activation in the dorsal horn of BV-inflamed rats.In addition,5,7-DHT pre-treated rats,compared with vehicle pre-treated ones,developed severe pain-related behaviors following BV intraplantar injection:duration of spontaneous flinching
作者
崔秀玉
关圆
Cui Xiu-Yu;Guan Yuan(Center of Parkinson's Disease,Beijing Institute for Brain Disorders,Capital Medical University,Beijing100069,China;Department of Anesthesiology,Beijing Huaxin Hospital,Beijing100016,China)
出处
《兰州大学学报（医学版）》
CAS
2019年第4期29-36,共8页
Journal of Lanzhou University（Medical Sciences）
基金
北京市教育委员会科技计划面上项目(KM201610025014)
