K物质在大鼠中脑导水管周围灰质中参与痛觉调制的作用

Effect of substance K on pain modulation in the periaqueductal gray of rats

目的:分析K物质在大鼠中脑导水管周围灰质中参与痛觉调制的作用,揭示内源性镇痛系统的神经递质机制。方法:实验于2004-03/09在武装警察部队医学院完成。选择6周龄雄性SD大鼠13只,实验过程中静脉持续给予戊巴比妥钠3～6mg/(kg·h)以维持大鼠浅麻状态,据鼠脑图谱确定中脑导水管周围灰质的坐标,采用核团内微量注射,以甩尾反射潜伏期为痛阈指标。K物质溶于0.01mmol/L的醋酸中,K物质注射量为1g/L,以辐射热照射大鼠尾端1/3部腹侧皮肤3mm×6mm。实验开始时调整电压强度,使甩尾反射潜伏期为3.5～4.5s。若甩尾反射潜伏期超过7s,则将辐射热源移开鼠尾,以免烫伤皮肤。间隔5min测1次甩尾反射潜伏期,实验开始时连续测定3次,取其均值作为基础对照值。以后测定9次。结果:实验动物13只在实验过程中无死亡,均进入结果分析。大鼠甩尾反射潜伏期基础对照值为(3.63±0.31)s。中脑导水管周围灰质内注入K物质后5,10,15,20,25,30min,甩尾反射潜伏期分别为(4.97±0.42)s,(5.63±0.48)s,(6.51±0.56)s,(5.06±0.41)s,(3.72±0.31)s,(3.66±0.29)s;中脑导水管周围灰质内注入K物质后5～20min甩尾反射潜伏期明显延长(t=9.25、12.25、16.23、10.03,P<0.001)。结论:K物质可能激活起自中脑导水管周围灰质的下行抑制通路,提示中脑导水管周围灰质在痛觉的下行抑制过程中起作用。

AIM： To analyze the effect of substance K on pain modulation in the periaqueduetal gray （PAG） of rats and indicate the neurotransmitter mechanism in endogenous analgesia system, METHODS： The experiment was performed at Medical College of Armed Police Force from March to September 2004, A total of 13 male SD rats aged six weeks were selected. Rats were initially anesthetized with 3-6 mg/kg per hour of pentobarbital sodium administered in vein. Coordinate of PAG was defined based on brain pattern of mice. Micro-injection was conducted in nucleus. Tail-flick latency （TFL） was as pain threshold index, Substance K was dissolved in 0.01 mmol/L ethanoic acid. and injection volume of substance K was 1 g/L. The 3 mm×6 mm third part of ventral skin to tail of rats was irradiated with radiant heat. The voltage was adjusted at the beginning of each experiment in order that the baseline TFL was from 3.5- 4,5 s. A cut-off time of 7 s was adopted to minimize damage to the skin, so mice tails were moved from radiant heat source, TFL was detected every 5 minutes. At the beginning, the TFL was determined 3 times sequentially, Their means were regarded as a control. In the following trials, detection was conducted for 9 times. RESULTS： Totally 13 experimental animals were involved in the result analysis, no drop-out, Basic control value of TFL in rats was （3.63±0.31） s, At 5, 10, 15, 20, 25, 30 minutes after substance K mieroinjected into the PAG, the：TFL was （4.97±0.42） s, （5.63±0.48） s, （6.51±0.56 ） s, （5.06±0.41 ） s, （3.72＋0.31） s, （3.66±0.29） s, respectively. The mieroinjection of substance K into PAG significantly increased TFL at 5-20 minutes （t=9.25, 12.25, 16.23, 10.03,P 〈 0,001）, CONCLUSION： Substance K may activate the descending inhibition approach from the PAG of rats, which indicates that the PAG plays effects in descending inhibition of algesthesis.