慢性疼痛对新生大鼠海马形态结构和学习记忆功能的影响

Effects of chronic pain on learning and memory and morphological structure of hippocampus in neonatal rats

目的 探讨慢性疼痛刺激对新生大鼠海马形态结构和学习记忆功能的影响。方法60只出生7 d SD大鼠,随机化区组实验设计,每天予以疼痛组(n=30)新生大鼠后脚掌注射0.5％福尔马林0.1 ml,连续两周至哺乳期结束;对照组(n=30)新生大鼠后脚掌则用棉签予以接触刺激。两周后用Morris水迷宫试验检测大鼠空间学习记忆功能的情况;水迷宫试验完成后,取两组大鼠海马组织,作病理切片,对海马齿状回颗粒细胞、CA3区锥体细胞进行计数,对海马CA3区锥体细胞超微结构进行观测。结果在Morris水迷宫试验中,疼痛组潜伏期明显长于对照组(P<0.01);与疼痛组比较,对照组海马齿状回单位面积的颗粒细胞数目、CA3区单位面积的锥体细胞数目显著性升高(P<0.01);对照组海马CA3区锥体细胞线粒体形态正常、线粒体嵴清晰可见,胞浆内粗面内质网丰富、清晰可见。疼痛组海马CA3区锥体细胞体积缩小,线粒体嵴及粗面内质网减少。结论 长期慢性疼痛刺激可抑制新生大鼠空间学习记忆功能的发育,可抑制新生大鼠海马齿状回颗粒细胞的发育,并引起海马CA3区锥体细胞丢失。

Objective It has been shown that strong acute stress or long-term chronic stress significantly affects learning and memory. The aim of this study was to investigate the effects of chronic pain on learning and memory and morphological structure of hippocampus in neonatal rats.Methods Sixty SD rats aged 7 days were randomly divided into two groups : (A) chronic pain group ( n = 30) in which 0.5% formalin 0.1 ml was injected subcutaneously into plantar region of hind paw every day for two weeks and (B) control group (n = 30) in which the plantar region of hind paw was touched with cotton-tipped swab every day for 2 weeks instead of subcutaneous injection of formalin. Morris water maze performance was used to test learning and memory. The number of granule neurons in dentate gyrus and pyramidal neurons in CA3 were counted. Results The mean latency period in the Morris water maze intelligence test was significantly longer in chronic pain group than that in control group ( P < 0.01). The number of granule neurons in dentate gyrus and pyramidal neurons in CA3 were significantly larger in control group than those in pain group ( P < 0.01) . The ultrastructure of CA3 pyramidal neurons showed that in control group the configuration of mitochondria was normal; mitochondrial crista was clear and rough endoplasmic reticulum was plenty and clear whereas in chronic pain group the cell body was smaller; mitochondria were swollen; mitochondrial crista was smaller and the number of rough endoplasmic reticulum was decreased. Conclusion Chronic pain can impair the development of spatial learning and memory and suppress the development of granule neurons in dentate gyms and cause loss of CA3 pyramidal neurons in neonatal rats.