Objective To observe the effects of peripheral tissue injury in the developmental stage of newborn rats on pain-related behaviors in adult rats.Methods SD rats 1,4,7,14,21 and 28 days after birth were selected in the present study (4 litters at each time point and 10 rats per litter).Each litter of rats was randomly divided into injury group (receiving subcutaneous injection of 20μl bee venom) and control group (receiving subcutaneous injection of 20μl normal saline),with 20 in each group,and then raised for 2 months to adulthood.The baseline pain threshold was observed by measuring spontaneous paw flinching reflex,paw withdrawal thermal latency (PWTL) and paw withdrawal mechanical threshold (PWMT),then 50μl 0.4％ bee venom was subcutaneously injected to each rat,and the changes in pain reaction and pain threshold were determined.Results The baseline thermal pain threshold in adult rats receiving bee venom or normal saline at different time points after birth was similar,but baseline mechanical pain threshold in adult rats receiving bee venom at 1,4,7 and 14 days after birth was decreased significantly compared with the adult rats receiving normal saline at corresponding time points(P＜0.01).The persistent spontaneous pain response of adult rats in injury group was increased compared with that in control group (P＜0.01).No obvious difference in heat hyperalgesia was found between the two groups (P＞0.05).Mechanical hyperalgesia was not induced in rats injected with bee venom but induced in adult rats injected with normal saline 4-21 days after birth.Injection of bee venom 21 and 28 days after birth could obviously enhance the bee venom-induced hyperalgesia in adult rats compared with control group (P＜0.01).Conclusions Bee venom stimuli at different time points after birth could affect the baseline PWMT and mechanical pain hypersensitivity in adult rats but not the baseline PWTL and thermal pain hypersensitivity.The 21st day maybe a key time point of nervous system development in rats.%目的 观察大鼠生后发育期外周组织损伤对其成年后痛行为的影响.方法 选取生后1、4、7、14、21、28d SD大鼠,每时间点4窝,每窝10只.每窝大鼠均随机均分为损伤组(皮下注射蜜蜂毒20μl,n=20)和对照组(皮下注射生理盐水20μl,n=20),饲养2个月至大鼠成年后,测定自发缩足反射次数、热刺激缩足反射潜伏期和机械刺激缩足反射阈值以反映大鼠成年后的基础痛阈,然后两组大鼠均给予0.4％蜜蜂毒50μl皮下注射,测定其痛反应性及痛阈改变情况.结果 大鼠生后不同时间给予蜜蜂毒或生理盐水处理,成年后基础热痛阈值无明显差异(P＞0.05),但生后21d前给予蜜蜂毒处理的大鼠成年后基础机械痛阈明显降低,与对照组比较差异显著(P＜0.01).损伤组大鼠成年后蜜蜂毒引起的持续自发痛反应与对照组比较明显增强(P＜0.01).生后1 ～ 28d给予蜜蜂毒或生理盐水处理的大鼠成年后原发性热痛敏无明显差别(P＞0.05),但生后4～21d给予蜜蜂毒处理的大鼠成年后并不诱致机械痛敏或触诱发痛,而生理盐水处理可引致成年后原发性机械痛敏.生后21、28d给予蜜蜂毒处理可显著增强成年后蜜蜂毒诱致的机械痛敏或触诱发痛,与对照组比较差异显著(P＜0.01).结论 大鼠生后发育期不同时间点给予蜜蜂毒伤害性刺激可明显影响其成年后的基础机械痛反射阈值和机械痛敏感性,但对成年后基础热痛潜伏期和热痛敏感性无显著影响.生后21d可能是大鼠神经系统发育过程中的一个关键时间点.
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