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链脲佐菌素诱导糖尿病大鼠的口腔面部感觉变化。

Orofacial sensory changes after streptozotocin-induced diabetes in rats.

机构信息

Department of Pharmacology Federal University of Parana, Biological Sciences Sector, Curitiba, PR, Brazil.

出版信息

Brain Res. 2013 Mar 21;1501:56-67. doi: 10.1016/j.brainres.2013.01.002. Epub 2013 Jan 8.

Abstract

Peripheral neuropathy is a common complication of diabetes and is often accompanied by episodes of pain. There is evidence that diabetic neuropathy may affect the trigeminal nerve, altering the transmission of orofacial sensory information. Structural changes in the trigeminal ganglia may be involved in the development of these sensory alterations. Herein, we evaluate the development of orofacial sensory changes after streptozotocin-induced diabetes in rats, and their sensitivity to pregabalin and morphine treatments. Furthermore, stereological analysis of the trigeminal ganglia was performed. Diabetic rats showed similar responses to 1% formalin applied into the upper lip compared to normoglycemic rats on weeks 1, 2 and 4 after streptozotocin. Additionally, there was no difference in the facial mechanical threshold of normoglycemic and diabetic rats, on weeks 1 up to 5 after streptozotocin, while the paw mechanical threshold of diabetic rats was significantly reduced. In contrast, diabetic rats developed long-lasting orofacial heat and cold hyperalgesia. Moreover, stereological analyses revealed significant neuronal loss in the trigeminal ganglia of diabetic compared to normoglycemic rats. Pregabalin treatment (30mg/kg, p.o.) of diabetic rats resulted in marked and prolonged (up to 6h) reduction of heat and cold orofacial hyperalgesia. Likewise, morphine treatment (2.5mg/kg, s.c.) abolished orofacial heat and cold hyperalgesia, but its effect was significant only up to 1h after the administration. In conclusion, the results of the present study demonstrated that streptozotocin-treated rats developed long-lasting orofacial heat and cold hyperalgesia, which is more amenable to reduction by pregabalin than morphine.

摘要

周围神经病变是糖尿病的常见并发症,常伴有疼痛发作。有证据表明,糖尿病性神经病可能影响三叉神经,改变口面部感觉信息的传递。三叉神经节的结构变化可能参与这些感觉改变的发展。在此,我们评估了链脲佐菌素诱导的糖尿病大鼠口面部感觉变化的发展及其对普瑞巴林和吗啡治疗的敏感性。此外,还对三叉神经节进行了体视学分析。糖尿病大鼠在链脲佐菌素后 1、2 和 4 周时,与正常血糖大鼠相比,对上唇 1%甲醛的反应相似。此外,正常血糖和糖尿病大鼠的面部机械阈值在链脲佐菌素后 1 周至 5 周时没有差异,而糖尿病大鼠的爪机械阈值显著降低。相比之下,糖尿病大鼠出现持久的口面部热和冷痛觉过敏。此外,体视学分析显示,与正常血糖大鼠相比,糖尿病大鼠的三叉神经节神经元明显丢失。普瑞巴林(30mg/kg,po)治疗糖尿病大鼠可显著且持久(长达 6 小时)减轻热和冷口面部痛觉过敏。同样,吗啡(2.5mg/kg,sc)治疗可消除口面部热和冷痛觉过敏,但仅在给药后 1 小时内效果显著。总之,本研究结果表明,链脲佐菌素处理的大鼠出现持久的口面部热和冷痛觉过敏,普瑞巴林对其的缓解作用优于吗啡。

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