Pharmacological sensitivity and gene expression analysis of the tibial nerve injury model of neuropathic pain
Pharmacological sensitivity and gene expression analysis of the tibial nerve injury model of neuropathic pain
复制标题
DOI：
10.1016/s0014-2999(03)01753-9
复制
发表时间：
2003-05-30
影响因子：
5
通讯作者：
Denzer, D
中科院分区：
文献类型：
--
作者：
Hofmann, HA;De Vry, J;Denzer, D
胫神经损伤模型是基于坐骨神经胫分支的单侧横断（神经切开术）的神经性疼痛的新的、手术简单的大鼠模型。本研究的目的是描述该模型的一些行为和分子特征，并测试其对目前用于治疗神经病理性疼痛的一些药物的敏感性。该模型的特征是所有受试者都存在明显的机械性异常性疼痛，而热痛觉过敏则不太强烈。机械性异常性疼痛在术后2周内发生，并可靠地存在至少9周。神经切断的大鼠没有表现出自切，其体重正常发展。在同侧L5背根神经节的基因表达，定量聚合酶链反应（PCR）分析，表现出显着的上调甘丙肽和血管肠肽（VfP）。这种上调迅速发展（神经切断术后1至2天内），并保持存在至少12天。另一方面，降钙素基因相关肽（CGRP）和P物质mRNA的表达下调神经切断后12天。机械性异常性疼痛被吗啡完全逆转[最小有效剂量（MED）：8 mg/kg，i. p.]并被卡马西平（MED：64 mg/kg，i. p.）部分逆转，巴氯芬（MED：3 mg/kg，i. p.）和阿米替林（32 mg/kg，i. p.下的疗效趋势），而加巴喷丁（50-100 mg/kg，i. p.）胫神经损伤模型显示出对许多已建立的镇痛剂敏感的稳健且持续的机械性异常性疼痛，以及与在其他神经性疼痛模型中获得的基因表达谱相容的基因表达谱，这一发现进一步支持其作为用于神经性疼痛研究的可靠且手术简单的模型的有效性。(C)2003 Elsevier Science B. V.保留所有权利。
The tibial nerve injury model is a novel, surgically uncomplicated, rat model of neuropathic pain based on a unilateral transection (neurotomy) of the tibial branch of the sciatic nerve. The aim of the present study was to describe some behavioral and molecular features of the model, and to test its sensitivity to a number of drugs which are currently used for the treatment of neuropathic pain. The model was characterized by a pronounced mechanical allodynia which was present in all subjects and a less robust thermal hyperalgesia. Mechanical allodynia developed within 2 weeks post-surgery and was reliably present for at least 9 weeks. Neurotomized rats showed no autotomy and their body weight developed normally. Gene expression in ipsilateral L5 dorsal root ganglia, analyzed by quantitative polymerase chain reaction (PCR), showed a pronounced up-regulation of galanin and vasointestinal peptide (VfP). This up-regulation developed rapidly (within 1 to 2 days following neurotomy) and remained present for at least 12 days. On the other hand, expression of calcitonin gene-related peptide (CGRP) and substance P mRNA was down-regulated 12 days following neurotomy. Mechanical allodynia was completely reversed by morphine [minimal effective dose (MED): 8 mg/kg, i.p.] and partially reversed by carbamazepine (MED: 64 mg/kg, i.p.), baclofen (MED: 3 mg/kg, i.p.) and amitriptyline (trend for efficacy at 32 mg/kg, i.p.), but not by gabapentin (50-100 mg/kg, i.p.). The finding that the tibial nerve injury model shows a robust and persistent mechanical allodynia which is sensitive to a number of established analgesics, as well as a gene expression profile which is compatible with that obtained in other models of neuropathic pain, further supports its validity as a reliable and surgically uncomplicated model for the study of neuropathic pain. (C) 2003 Elsevier Science B.V. All rights reserved.