大鼠PAG内Nogo-A和CGRP参与痛觉调制的研究

Study of Nogo-A and CGRP involved in pain modulation in PAG of rat

目的:探讨Nogo-A在痛觉调制过程中的作用以及它在大鼠中脑导水管周围灰质(periaqueductal gray,PAG)内与降钙素基因相关肽(CGRP)和内源性阿片系统在痛觉调制过程中的相互关系。方法:选用雄性SD大鼠32只,随机等分为4组:其中空白对照组8只,分别向PAG内注射0.9%生理盐水1μl;痛敏模型对照组、吗啡组和纳洛酮组各8只,首先单侧后爪掌心皮下注射1%的福尔马林0.1 ml复制痛敏大鼠模型,3 d后分别向PAG内注射等量0.9%生理盐水、吗啡和纳洛酮各1μl。60 min后取大鼠大脑PAG区,采用免疫组化法观测各组大鼠PAG内CGRP和Nogo-A免疫反应阳性神经元的表达差异。结果:与空白对照组比较,模型对照组大鼠PAG内CGRP的表达量显著增高(P<0.01),Nogo-A显著降低(P<0.01);与模型对照组比较,吗啡组大鼠PAG内CGRP的表达量显著降低(P<0.05),Nogo-A显著增高(P<0.01),而纳洛酮组PAG中CGRP的表达量显著增高(P<0.01),Nogo-A显著降低(P<0.05)。结论:Nogo-A和CGRP参与了痛觉调制过程,但Nogo-A与CGRP之间有反向调节作用;Nogo-A与内源性阿片系统之间可能也存在一定的功能联系。

Objective：To investigate the role of Nogo-A in pain modulation,and the relationship of Nogo-A with calcitonin gene-related peptide（CGRP） and endogenous opioid system in periaqueductal gray（PAG） of hyperalgesia rats.Methods：32 male SD rats were randomly divided into four groups：Rats in control group received intra-PAG injection of 0.9% saline（1 μl）;Rats in model group,morphine group and naloxone group received unilateral hindpaw hypodermic injection of 1% formalin（0.1 ml） to prepare pain model,then received intra-PAG injection of 0.9% saline 1 μl,morphine 1 μl and naloxone 1 μl respectively 3 days later.After 60 minutes,the PAG area of rats were removed,the expression differences of CGRP and Nogo-A in PAG of rats in each group were observed and measured by immunohistochemical method.Results：The expression of CGRP immunoreactivity in PAG area of model group was obviously increased than that of control group（P0.01）,but Nogo-A was obviously reduced（P0.01）;The expression of CGRP immunoreactivity in PAG area of morphine group was obviously reduced than that of model group（P0.05）,but Nogo-A was obviously increased（P0.01）;The expression of CGRP immunoreactivity in PAG area of naloxone group was obviously increased than that of model group（P0.01）,but Nogo-A was obviously reduced（P0.05）.Conclusion：Nogo-A and CGRP were both involved in pain modulation,but the effect of Nogo-A was contrast with that of CGRP,Nogo-A and endogenous opioid systems may also have some functional relationship.