Neonatal immune challenge alters nociception in the adult rat
Neonatal immune challenge alters nociception in the adult rat
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DOI：
10.1016/j.pain.2005.09.022
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发表时间：
2005-12-15
期刊：
影响因子：
7.4
通讯作者：
Pittman, QJ
中科院分区：
文献类型：
--
作者：
Boissé, L;Spencer, SJ;Pittman, QJ
在发育过程中经历的剧烈疼痛或剧烈外周炎症可能对成人痛觉产生明显影响。然而，很少有人知道更常见的轻度全身性炎症，如轻度疾病。新生儿暴露于脂多糖（LPS），免疫系统激活的一个既定模型，已被证明会影响发热和环氧合酶-2（考克斯-2）反应，以类似的暴露在成年期。成年LPS还诱发一系列疾病行为，包括对疼痛刺激的增强反应。因此，我们假设成年人的感觉和疼痛反应可能会受到新生儿LPS挑战的影响。雄性和雌性Sprague-Dawley大鼠在出生后第14天给予LPS，并在成年期分别使用足底测试装置和von Frey细丝在成年LPS之前和之后测试对热刺激和机械刺激的伤害性反应。同时检测背根神经节和腰髓考克斯-2的表达。用盐水处理的新生动物在成年LPS后显示出对疼痛刺激的预期超敏反应以及脊髓考克斯-2的增强。然而，新生儿LPS治疗的大鼠表现出显着不同的配置文件。与生理盐水处理的大鼠相比，它们表现出增强的基线伤害感受和升高的基底脊髓考克斯-2。此外，而不是预期的痛觉过敏后，成人LPS，没有变化的伤害性反应和脊髓考克斯-2的表达减少进行了观察。这些发现对理解疼痛及其管理具有重要意义，并强调了新生儿期在疼痛通路发展中的重要性。(c)2005年国际疼痛研究协会。Elsevier B. V.出版，保留所有权利。
Intense pain or intense peripheral inflammation experienced during development can have pronounced effects upon adult pain sensation. However, little is known about the more commonly encountered mild systemic inflammation, such as that experienced with mild illness. Neonatal exposure to lipopolysaccharide (LPS), an established model of immune system activation, has been shown to affect febrile and cyclooxygenase-2 (COX-2) responses to a similar exposure in adulthood. Adult LPS also elicits a range of sickness behaviours, including enhanced responses to painful stimuli. We, therefore, hypothesized that adult sensation and pain responses could be affected by a neonatal LPS challenge. Male and female Sprague-Dawley rats were administered LPS at postnatal day 14 and were tested in adulthood for nociceptive responses to thermal and mechanical stimuli using, respectively, a plantar test apparatus and von Frey filaments, before and after adult LPS. Expression of dorsal root ganglion and lumbar spinal cord COX-2 was also examined. Animals treated as neonates with saline showed the expected hypersensitivity to painful stimuli after adult LPS as well as enhanced spinal cord COX-2. Neonatally LPS-treated rats, however, showed a significantly different profile. They displayed enhanced baseline nociception and elevated basal spinal cord COX-2 compared with neonatally saline-treated rats. Also, rather than the expected hyperalgesia after adult LPS, no changes in nociceptive responses and a reduction in spinal cord COX-2 expression were observed. These findings have important implications for the understanding of pain and its management and highlight the importance of the neonatal period in the development of pain pathways. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.