鞘内预注CRH对甲醛炎性反应性大鼠脊髓痛觉敏化的影响

Antinociceptive effect of pre-emptive intrathecal administration of CRH in rats following formalin-induced information pain

目的研究鞘内预注促肾上腺皮质激素释放激素(corticotropin releasing hormone/factor,CRH/CRF)以及联合芬太尼对足底注射甲醛诱导的大鼠脊髓痛觉敏化的影响。方法采用甲醛炎性反应性痛模型,大鼠随机分为5组,分别于甲醛刺激前10min鞘内预注:生理盐水20μL;CRH 0.5μg;芬太尼0.25μg;CRH 0.5μg+芬太尼0.25μg;提前1h腹腔内注射CP-154526(10mg/kg)后鞘内给予CRH 0.5μg。各组分别在15、30、60、120min共4个时相点检测热辐射刺激甩尾反射潜伏期即痛阈的变化,并于2h后检测脊髓后角原癌基因c-fos的表达产物Fos蛋白的表达情况。结果鞘内预注CRH 0.5μg抑制痛阈的下降,同时可以抑制脊髓后角浅层Fos蛋白的表达效应,并显著增强芬太尼的作用。提前1h腹腔内注射CP-154526可抵消这种抑制效应。结论在脊髓水平给予CRH可抑制脊髓痛觉敏化,并加强芬太尼的镇痛效应。

Objective To investigate the antinociceptive effect of pre-emptive intrathecal administration of CRH on hyperalgesia of rats following formalin-induced inflammatory pain. Methods SD rats were randomly divided into 5 groups with eight in each group. Animals were injected intrathecally with normal saline 20uL （NF group）, CRH 0. 5ug （CF group）, fentanyl 0. 25ug （TF group）, CRH 0.5ug＋ fentanyl 0.25ug（CTF group）, and CRH 1 type receptor specific blocker CP-154526 （ 10mg/kg, intraperitoneally） Was used lh in advance,then CRH 0.5ug（CPF group）. Animal models were made by subcutaneous injecting 5% formalin （0. lmL） into the plantar region of the right hindpaw. Every experimental group received saline,CRH or fentanyl 10min before formalin injection. The pain threshod of ratsl was observed at 15,30,60,120min after formalin injection. The c-fos gene expression in the dorsal horn of spinal cord was analyzed by immunohistochemical technique and computer image technique. Results The pain threhold of the rats was significantly decreased（P〈0.05） at 15,30,60,120min after formalin injection, which was showed that hyperalgesia was occurred. Administration of CRH（0.5ug） reduced（P〈0.05） the hyperalgesia and the combination of CRH＋ fentanyl exerted most powerful effects on the pain threshold. Conclusion Pre-emptive intrathecal administration of CRH could inhibit the hyperalgesia of rats and potentiate the effect of fentanyl because of its potence of inhibiting hyperalgesia induced by inflammatory stimulation.