无痛注射选择性5-羟色胺再吸收抑制剂与盐酸利多卡因缓解新生大鼠疼痛的机制

Mechanism of Indolent Injection of Selective Serotonin Reuptake Inhibitors and Lidocaine to Relieve Pain Perception in Neonatal Rats

目的探讨无痛注射选择性5-羟色胺再吸收抑制剂(SSRI)与盐酸利多卡因缓解新生大鼠疼痛时疼痛部位5-羟色胺1A(5-HTIA)的表达及同期脑啡肽的表达。方法将14日龄新生SD大鼠随机分为对照组、盐酸氟西汀(SSRI)组、盐酸利多卡因组,每组10只。用血糖针针尖完全刺入新生SD大鼠臀部作为疼痛刺激,针刺后立即用injex无针注射笔在针刺部位分别注射9 g·L-1盐水、SSRI药液及盐酸利多卡因药液,处死大鼠,取其臀部皮肤组织进行石蜡包埋,免疫组织化学法检测其局部5-HTIA分布部位,通过图像分析系统分析5-HTIA水平,同时取其全脑匀浆,离心后用酶联免疫吸附法检测其脑啡肽水平。结果疼痛刺激试验完成前各实验组均无5-HTIA阳性颗粒表达;试验后各实验组皮肤组织表皮质均有5-HTIA阳性颗粒表达;SSRI组5-HTIA阳性反应区明显大于对照组和盐酸利多卡因组。免疫组织化学法检测显示5-HTIA在SSRI组为0.241 5±0.020 5,显著高于对照组(0.204 9±0.016 4)(P<0.01),也显著高于盐酸利多卡因组(0.168 1±0.022 1)(P<0.01)。SSRI组新生大鼠全脑匀浆脑啡肽(39.706±2.864)ng·L-1,明显高于对照组[(36.627±2.151)ng·L-1](P<0.05);盐酸利多卡因组为(39.087±3.577)ng·L-1,也明显高于对照组(P<0.05);SSRI组和利多卡因组脑啡肽表达比较无差异。结论无痛注射SSRI缓解疼痛的机制可能是通过抑制皮肤神经接头处5-HTIA的再吸收而抑制疼痛的神经传导。无痛注射SSRI和盐酸利多卡因最终均是通过增加脑啡肽而发挥镇痛作用。

Objective To investigate the expressions of 5 - hydroxy tryptamine（5 - HT） and enkephalin in neonatal rats after indolent injection with the selective serotonin reuptake inhibitor （SSRI） and ]iducainc which could relieve pain perception. Methods Neonatal SD rats （14 days） were divided into control group,fluoxetine （SSRI） group and lidoeainc group（10 cases in each group） randomly. Pain percep- tion of rats in each group was stimulated with the tip of a blood glucose needle, hnmediately after stimulating,saline,SSR1 or lidocaine was in- jected by using an injex pen without needle at the same area for each group. Pain stimulation test before and ＇after neonatal SD rats breathing, heart rate, screaming frequency and tail -flicking frequency were tested. Then after the physieal index observed, the rats were sacrificed for de- tecting the 5 -hydroxytryptaminc reeeptor 1 （5 -HT1A ） distribution by immunohistoehemistry in hip skin and enkephalin content by enzyme - linked immunosorbent method in brain. Results Immunohistochemistry analysis showed 5 - HT1A was significantly higher in the epidermis of rat skin after SSRI indolent injection（0. 241 5±0. 020 5 ） than that in lidocaine group （0.168 1±0. 022 1, P 〈 0.01 ） and control group （0. 204 9 ±0. 016 4,P 〈0.01 ）. SSRI indolent injection caused a higher level of enkephalin content I （39. 706±2. 864） ng · L^-1 in rats brain homogenate than that in control gruup [ （36. 627±2. 151 ）ng ·L^-1 （P 〈 0.05 ）, and the level of enkephalin contenl in lidoeaine group was （ 39. 087±3. 577 ） ng·L^-1, which was also higher than that in control group （ P 〈 0.05 ） , but there was no significant difterencc between SSRI group and lidocaine group. Conclusions The mechanism of SSRI indolent injection relieves pain perception by inhibiting 5-HT1A reab- sorption at the skin nerve joints so to inhibit the nerve conduction of pain. Both SSRI and lidoeaine exert the analgesic effect both by increasing enkephalin content in cerebrum.