幼鼠内脏痛觉高敏感性与脊髓降钙素基因相关肽表达的关系

摘要

目的 探讨脊髓降钙素基因相关肽(CGRP)参与幼鼠痛觉高敏感形成的可能机制.方法 8日龄新生SD大鼠分成4组,每组8只.A1B1组新生期给予结直肠扩张刺激(CI),并在6周龄时给予结直肠扩张(CRD)刺激;A1B2组新生期给予CI,6周龄时不予CRD刺激;A2B1组新生期未接受CI,6周龄时给予CRD刺激;A2B2组新生未接受CI,6周龄时也未给予CRD刺激.A1B1组和A1B2组乳鼠在出生后8 ～ 15 d,每天接受1次CI.常规喂养至6周龄,A1B1组和A2B1组幼鼠进行CRD刺激下内脏痛敏感性评价.之后采用SABC免疫组化法检测4组幼鼠脊髓内CGRP表达情况.结果 随CRD增加,A1B1组和A2B1组幼鼠腹外斜肌放电波幅均逐渐增加.CRD在15、30、45、60 mmHg时,A1B1组腹外斜肌放电幅值明显高于A2B1组,CRD 75 mmHg时,两组腹外斜肌放电幅值差异无统计学意义.新生期CI和接受伤害性CRD刺激后可导致幼鼠脊髓内CGRP阳性细胞数明显增加.结论 新生期持续CI会造成幼鼠痛阈下降,出现慢性内脏高敏感性.幼鼠慢性内脏痛敏感性异常可能与脊髓内CGRP异常表达相关;CGRP可能作为一种神经递质参与内脏痛觉敏感的改变.%Objective To establish the model of visceral hyperalgesia in young rats.To explore the role of abnormal expression of calcitonin gene related peptide ( CGRP) in forming the visceral hyperalgesia in young rats.Methods Eight-day-old Sprague-Dawley rats were divided into four groups (n = 8 for each) : rats of group A1B1 were imposed on colorectal irritation (CI) at neonatal period and imposed on colorectal distension (CRD) at 6-week age; rats of group A1B2 were imposed on CI at neonatal period and without being imposed on CRD at 6-week age; rats of group A2B1 were not impose on CI at neonatal period and were imposed on CRD at 6-week age; rats of group A2B2 were neither imposed on CI at neonatal period nor CRD at 6-week age.Group A1B1 and group A1B2 were treated with CI once a day for 7 consecutive days from the 8th day after birth.Conventionally breeding till the young period (6-week age) , the visceral sensitivity of group A1B1 and group A1B2 was evaluated.Then, SABC immunohistochemical assay was used to detect the expression of CGRP in spinal cord of all rats in four groups.Results The amplitudes of spike EOMA increased gradually with the rising of the CRD pressure in young rats.When the CRD pressure were 15 mmHg, 30 mmHg, 45 mmHg and 60 mmHg, the spikes were significantly higher in the group A1B1 than group A2B1.When pressure were 75 mmHg, the differences were not statistically significant.Rats accepted CI in neonatal period and noxious stimulation of CRD could make the number of CGRP-like immunoreactivity increased in the spinal cord of young rat.Conclusions The persistent CI in neonatal period can result in low pain threshold and chronic high visceral pain sensibility in developing rats.Rats with abnormal chronic visceral pain may involve the abnormal expressing of CGRP in spinal cord.CGRP as a neurotransmitter, may involve in the changing of visceral pain sensitivity.