Normal hypothalamo-pituitary-adrenal axis function in a rat model of peripheral neuropathic pain
Normal hypothalamo-pituitary-adrenal axis function in a rat model of peripheral neuropathic pain
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DOI：
10.1016/j.brainres.2005.03.005
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发表时间：
2005-05-24
期刊：
影响因子：
2.9
通讯作者：
Blackbum-Munro, G
中科院分区：
文献类型：
--
作者：
Bomholt, SF;Mikkelsen, JD;Blackbum-Munro, G
慢性疼痛病症如类风湿性关节炎和纤维肌痛与严重的下丘脑-垂体-肾上腺（HPA）轴功能障碍相关，这可能会加剧慢性疼痛的症状。HPA轴功能障碍在慢性炎性疼痛的动物模型中也有很好的记录。然而，HPA轴在神经性疼痛动物模型中的作用目前尚不清楚。大鼠坐骨神经慢性压迫性损伤（CCI），开发显着的机械异常性疼痛和痛觉过敏的受伤后爪被用来确定基础和刺激水平的HPA轴活动。CCI大鼠束缚应激20 min后血浆ACTH和皮质酮水平较应激前显著升高（P < 0.05），但升高幅度与假手术组无明显差异。此外，CCI和假手术大鼠在束缚终止后60分钟内的促肾上腺皮质激素释放时间曲线相似，表明糖皮质激素介导的反馈正常。束缚应激也显著增加（P < 0.05）CCI和Sham大鼠下丘脑室旁核内即刻早期基因c-Fos和FosB的表达，但增加程度相似。在小细胞PVN内CRF和AVP mRNA的基础表达在CCI和Sham大鼠之间没有差异;束缚应激仅在Sham大鼠中诱导CRF mRNA表达显著增加2.5倍（P < 0.05）。这些结果表明，在炎症免疫介导的疼痛模型中，HPA轴功能被深刻地改变，在CCI模型的神经性疼痛，基础HPA轴功能是不变的。此外，HPA轴在面对持续的伤害性输入时对新的应激源正常反应，这种刺激已知会激活HPA轴。(c)2005 Elsevier B. V.保留所有权利。
Chronic pain conditions such as rheumatoid arthritis and fibromyalgia are associated with profound hypothalamo-pituitary-adrenal (HPA) axis dysfunction which may exacerbate symptoms of chronic pain. HPA axis dysfunction has also been well documented in animal models of chronic inflammatory pain. However, the role of the HPA axis in animal models of neuropathic pain is currently unknown. Rats with a chronic constriction injury (CCI) of the sciatic nerve that developed marked mechanical allodynia and hyperalgesia of the injured hindpaw were used to determine basal and stimulatory levels of HPA axis activity. Plasma ACTH and corticosterone levels were increased significantly (P < 0.05) in CCI rats after 20 min restraint stress compared with baseline; however, the magnitude of the increase was no different from sham rats. Furthermore, the temporal profile of ACTH release over the 60 min period after termination of restraint was similar between CCI and sham rats suggesting normal glucocorticoid-mediated feedback. Restraint stress also significantly increased (P < 0.05) expression of the immediate early genes c-Fos and FosB within the hypothalamic PVN to a similar extent in CCI and sham rats. Within the parvocellular PVN basal expression of both CRF and AVP mRNA was no different between CCI and sham rats; restraint stress induced a significant 2.5 fold increase (P < 0.05) in CRF mRNA expression in sham rats only. These results suggest that, in contrast to inflammatory immune-mediated pain models where HPA axis function is profoundly altered, in the CCI model of neuropathic pain, basal HPA axis function is unchanged. Furthermore, the HPA axis responds normally to a novel stressor in the face of ongoing nociceptive input, a stimulus known to activate the HPA axis. (c) 2005 Elsevier B.V. All rights reserved.