The role of nitric oxide and prostaglandin signaling pathways in spinal nociceptive processing in chronic inflammation
The role of nitric oxide and prostaglandin signaling pathways in spinal nociceptive processing in chronic inflammation
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DOI：
10.1016/s0304-3959(00)00262-1
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发表时间：
2000-06-01
期刊：
影响因子：
7.4
通讯作者：
Nolan, AM
中科院分区：
文献类型：
--
作者：
Dolan, S;Field, LC;Nolan, AM
一氧化氮（NO）和前列腺素（PG）及其相关酶一氧化氮合酶（NOS）和环氧合酶（COX）（特别是COX-2）都与痛觉过敏的发生有关。本研究考察了自然发生的慢性炎症（慢性乳腺炎）对绵羊脊髓伤害性加工的影响，并重点研究了脊髓PG和NO信号通路的潜在改变。患有慢性炎症的动物（n = 6）的机械戒断阈值明显低于对照组动物（n = 6）。痛觉过敏局限于炎症对侧（同侧减少：后肢33.2 +/- 5%，前肢19.4 +/- 5%）。与对照动物相比，乳腺炎动物腰、颈脊髓I-m层神经元nos免疫反应性显著降低（分别降低18.4 +/- 5%和16.9 +/- 4%），X层神经元nos免疫反应性显著降低（分别降低29.1 +/- 6%和17.1 +/- 4%）。在eNOS或iNOS免疫反应性以及NADPH-diaphorase染色（动态活性NOS的标志）中未检测到差异。RT-PCR未检测到nNOS、eNOS、iNOS、cox - 1或COX-2 mrna水平的任何变化。然而，在慢性炎症动物的同侧脊髓组织中检测到PGE受体EP3（而非EP2） mRNA的显著增加。EP3受体表达的增加表明脊髓pg在脊髓对慢性外周炎症的反应中很重要。对侧机械性痛觉过敏可能与脊髓EP3受体mRNA表达的变化没有直接联系，然而，双侧nNOS的变化表明，这一途径可能有助于观察到的适应性行为反应。(C) 2000国际疼痛研究协会。Elsevier Science B.V.版权所有。
Both nitric oxide (NO) and prostaglandins (PG) and their associated enzymes nitric oxide synthases (NOS) and cyclooxygenases (COX) (specifically COX-2) have been implicated in the development of hyperalgesia. This study examined the effects of naturally occurring chronic inflammation, chronic mastitis, on spinal nociceptive processing in sheep and focused on potential alterations in spinal PG and NO signaling pathways. Mechanical withdrawal thresholds were significantly lower in animals suffering from chronic inflammation (n = 6) compared to control animals (n = 6). Hyperalgesia was restricted to the side contralateral to the inflammation (decrease from ipsilateral side: hindlimb 33.2 +/- 5%, forelimb 19.4 +/- 5%). Neuronal NOS-immunoreactivity was significantly reduced bilaterally in lumbar and cervical spinal cord throughout laminae I-m (decrease 18.4 +/- 5% and 16.9 +/- 4%, respectively) and in lamina X (decrease 29.1 +/- 6% and 17.1 +/- 4%, respectively) in mastitic animals relative to control animals. No difference was detected in eNOS or iNOS-immunoreactivity or in NADPH-diaphorase staining, a marker of dynamically active NOS. RT-PCR failed to detect any change in levels of nNOS, eNOS, iNOS, COX-I or COX-2 mRNAs. However, a marked increase in the PGE receptor, EP3 (but not EP2) mRNA was detected in ipsilateral spinal cord tissue from animals with chronic inflammation. This increase in EP3 receptor expression indicates that spinal PGs are important in the spinal response to chronic peripheral inflammation. Contralateral mechanical hyperalgesia may not be directly linked to changes in spinal EP3 receptor mRNA expression, however, the bilateral changes in nNOS suggest that this pathway may contribute to the adaptive behavioural response observed. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.