H3受体在5-羟色胺诱导大鼠瘙痒初级传入通路中作用

ROLE OF H3 RECEPTORS IN PRIMARY AFFERENT PATHWAY OF 5-HT-INDUCED ITCH IN RATS

目的观察H3受体激动剂(R-α-甲基组胺)和拮抗剂(噻普酰胺)对5-羟色胺(5-HT)诱导大鼠搔抓行为的影响,并探讨H3受体在大鼠瘙痒初级传入通路中的作用。方法29只SD大鼠随机分为4组,分别在颈背部皮内注射生理盐水(生理盐水组)、2%5-HT(5-HT组)、R-α-甲基组胺+5-HT(甲基组胺组)、噻普酰胺+5-HT(噻普酰胺组),摄像并计数注射后1 h内搔抓次数。取大鼠C3-C5及其相应节段的背根神经节(DRG)作H3R免疫组化染色。结果5-HT组大鼠的搔抓次数明显多于生理盐水组(P<0.01),而R-α-甲基组胺或噻普酰胺预处理可分别减少或增加大鼠搔抓次数(P<0.01)。5-HT组大鼠脊髓后角浅层中H3受体表达与生理盐水组相比差异无显著性(P>0.05),而R-α-甲基组胺或噻普酰胺预处理可分别减少或增加H3受体表达(P<0.01-0.05)。各组动物DRG内,H3受体阳性中、小型神经细胞的比值差异无统计学意义(P>0.05)。结论在5-HT诱导大鼠急性瘙痒模型中,脊髓背角胶状质区内H3受体激活可减弱瘙痒,但DRG内中、小型神经细胞上H3受体表达可能不参与瘙痒信号的传导。

Objective To observe the effect of H3 receptor（H3R） agonist（R-α-methylhistamine） and antagonist（thioperamide） on 5-HT-induced scratching behaviors of rats and to study the role of H3R in the primary afferent pathway of itch in the animal model.MethodsTwenty-nine SD rats were randomly divided into 4 groups,and received intradermal injection of normal saline（NS group）,2% 5-HT（5-HT group）,thioperamide ＋ 5-HT（thioperamide group）,and R-α-methylhistamine ＋ 5-HT（MH group） in the rostral part of the back.Scratching bouts to the injected site during 1 hour after injection were counted with digital videotape.The spinal cord C3-C5 and corresponding dorsal root ganglia（DRG） were stained immunohistochemically with the polyclonal antibody to H3R.ResultsIncreased scratching bouts were found in the animals of the 5-HT group in comparison to those in the NS group（P〈0.01）.Pretreatment with R-α-methylhistamine decreased the scratching bouts,but thioperamide enhanced the bouts（P〈0.01）.H3R expression in the superficial layer of dorsal horn was not significantly changed in the 5-HT group,but was remarkably increased in the thioperamide group and decreased in the MH group.The ratio of small to middle H3R immunoreactive neurons in DRG showed no statistical difference among 4 groups.ConclusionH3R activation in the gelatinous substance of dorsal horn may attenuate the 5-HT-induced itching in rats.H3R expression on the small to middle neurons in DRG might not be involved in the transmission of pruritic signals.