Priming enhances endotoxin-induced thermal hyperalgesia and mechanical allodynia in rats
Priming enhances endotoxin-induced thermal hyperalgesia and mechanical allodynia in rats
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DOI：
10.1016/s0006-8993(98)00786-0
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发表时间：
1998-10-12
期刊：
影响因子：
2.9
通讯作者：
Coderre, TJ
中科院分区：
文献类型：
--
作者：
Cahill, CM;Dray, A;Coderre, TJ
中枢炎症是许多衰弱性疾病的病理学的组成部分和贡献者，并且已显示产生自发性疼痛和痛觉过敏。最近，大鼠侧脑室注射脂多糖（LPS）可引起热痛觉过敏和触觉异常性疼痛[K。步行者，A.德雷，M. Perkins，脑室内给予内毒素后大鼠的痛觉过敏：缓激肽B（1）和B（2）受体拮抗剂治疗的作用，Pain 65（1996）211-219]。在这项研究中，我们复制了LPS模型与一些调整和相关的伤害性行为与激活的巨噬细胞在中枢神经系统中的表达增加。我们还研究了引发对LPS诱导的热伤害性阈值和机械反应阈值降低的影响，无论是中枢还是外周给药，脑室内（i. c. v.）与注射后最初几小时的基线值相比，给予LPS（0.2 μ g/大鼠）没有改变热（热板）或机械（vonFrey细丝）阈值。然而，通过在用i. c. v. LPS（0.2 μ g）测试之前24小时用i. c. v. LPS（0.2 μ g）预处理来引发大鼠产生显著的机械异常性疼痛和热痛觉过敏。机械性异常性疼痛在注射后80 min开始，持续时间为5 h。观察到类似的时间过程的热痛觉过敏，虽然它的表达不太明显。免疫组织化学研究表明，激活的巨噬细胞在致敏大鼠的脑实质中的表达增加，但在未致敏大鼠中没有。腹膜内（i. p.，在注射后的最初几个小时内，给予LPS（0.2 mg/kg）对热阈值或机械阈值没有显著影响;然而，通过腹腔内（0.2 mg/kg）或静脉内（0.2 μ g）LPS致敏大鼠在随后腹腔内注射LPS的大鼠中产生热伤害感受阈值和机械反应阈值的降低。本研究表明，预激是诱导中枢炎症的有效方案，并增加了i. c. v.给药后这些行为的持续时间。(C)1998年由Elsevier Science B. V.出版，版权所有。
Central inflammation is an integral component and contributor of the pathology of many debilitating diseases and has been shown to produce spontaneous pain and hyperalgesia. Recently, administration of lipopolysaccharide (LPS) into the lateral ventricle of rats was shown to elicit both thermal hyperalgesia and tactile allodynia [K. Walker, A. Dray, M. Perkins, Hyperalgesia in rats following intracerebroventricular administration of endotoxin: effect of bradykinin B(1) and B(2) receptor antagonist treatment, Pain 65 (1996) 211-219]. In this study, we have replicated the LPS model with some adaptations and correlated the nociceptive behaviors with an increased expression of activated macrophages in the central nervous system. We also examined the effects of priming on LPS-induced decreases in thermal nociceptive thresholds and mechanical response thresholds following either central or peripheral administration, Intracerebroventricular (i.c.v.) administration of LPS (0.2 mu g/rat) did not alter either thermal (hot plate) or mechanical (von Frey filaments) thresholds compared to baseline values in the first few hours after injection. However, priming rats by pretreating with i.c.v, LPS (0.2 mu g) 24 h prior to testing with i.c.v. LPS (0.2 mu g) produced significant mechanical allodynia and thermal hyperalgesia. The mechanical allodynia had an onset of 80 min after injection and a duration of 5 h. A similar time course was observed for thermal hyperalgesia, although its expression was less pronounced. Immunohistochemical studies indicated an increased expression of activated macrophages in the brain parenchyma of primed rats but not in unprimed rats. Intraperitoneal (i.p., 2 mg/kg) administration of LPS had no significant effect on either thermal or mechanical thresholds in the first few hours after injection; however, priming rats via i.p. (0.2 mg/kg) or i.c.v, (0.2 mu g) LPS produced a reduction in both thermal nociceptive thresholds and mechanical response thresholds in rats given a subsequent i.p. injection of LPS. This study demonstrates that priming is an effective protocol for the induction of central inflammation and increases the duration of these behaviors after i.c.v. administration. (C) 1998 Published by Elsevier Science B.V. All rights reserved.