Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury.
Up-regulation of platelet-activating factor synthases and its receptor in spinal cord contribute to development of neuropathic pain following peripheral nerve injury.
复制标题
DOI：
10.1186/1744-8069-8-8
复制
发表时间：
2012-02-02
期刊：
影响因子：
3.3
通讯作者：
Noguchi K
中科院分区：
文献类型：
--
作者：
Okubo M;Yamanaka H;Kobayashi K;Kanda H;Dai Y;Noguchi K
血小板活化因子(PAF；1-烷基-2-乙酰-SN-甘油-3-磷酸胆碱)是一种来源于细胞膜的脂质介质。据报道，PAF参与了多种病理情况，如脊髓损伤、多发性硬化症、神经病理性疼痛以及鞘内应用PAF导致触觉超敏。然而，周围神经损伤后PAF合酶及其受体在脊髓中的表达尚不清楚。采用大鼠备用神经损伤(SNI)模型，观察PAF合成酶(LPCAT1和LPCA2)和PAF受体(PAFR)在脊髓中的表达。采用逆转录-聚合酶链式反应(RT-PCR)和原位杂交组织化学(ISHH)与免疫组织化学(IHC)双标记分析方法进行分析。用PAFR拮抗剂(WEB2086)观察疼痛行为。RT-PCR结果显示损伤侧脊髓LPCAT2基因表达增加，而LPCAT1基因表达无明显变化。免疫组化双标记法显示，神经损伤后LPCAT1和2mRNAs在部分神经元中呈结构性表达，LPCAT2在脊髓小胶质细胞中表达增加。逆转录-聚合酶链式反应显示，神经损伤后同侧脊髓组织PAFR基因表达显著增加。免疫组织化学双标记法显示，脊髓损伤后，PAFR mRNA主要与小胶质细胞共存。鞘内持续给予PAFR拮抗剂可抑制周围神经损伤后的机械性痛觉过敏。延迟给予PAFR拮抗剂并不能逆转机械性异位痛觉。我们的数据显示了周围神经损伤后PAF合成酶及其受体在脊髓中的组织学定位，提示脊髓中的PAF/PAFR信号在激活的小胶质细胞和神经元之间以自分泌或旁分泌的方式发挥作用，从而促进神经病理性疼痛的发生。
Platelet-activating factor (PAF; 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a lipid mediator derived from cell membrane. It has been reported that PAF is involved in various pathological conditions, such as spinal cord injury, multiple sclerosis, neuropathic pain and intrathecal administration of PAF leads to tactile allodynia. However, the expression of PAF synthases and its receptor in the spinal cord following peripheral nerve injury is unknown. Using the rat spared nerve injury (SNI) model, we investigated the expression of PAF synthases (LPCAT1 and 2) and PAF receptor (PAFr) mRNAs in the spinal cord. Reverse transcription polymerase chain reaction (RT-PCR) and double-labeling analysis of in situ hybridization histochemistry (ISHH) with immunohistochemistry (IHC) were employed for the analyses. Pain behaviors were also examined with PAFr antagonist (WEB2086). RT-PCR showed that LPCAT2 mRNA was increased in the ipsilateral spinal cord after injury, but not LPCAT1 mRNA. Double-labeling of ISHH with IHC revealed that LPCAT1 and 2 mRNAs were constitutively expressed by a subset of neurons, and LPCAT2 mRNA was increased in spinal microglia after nerve injury. RT-PCR showed that PAFr mRNA was dramatically increased in the ipsilateral spinal cord after nerve injury. Double-labeling analysis of ISHH with IHC revealed that after injury PAFr mRNA was predominantly colocalized with microglia in the spinal cord. Continuous intrathecal administration of the PAFr antagonist suppressed mechanical allodynia following peripheral nerve injury. Delayed administration of a PAFr antagonist did not reverse the mechanical allodynia. Our data show the histological localization of PAF synthases and its receptor in the spinal cord following peripheral nerve injury, and suggest that PAF/PAFr signaling in the spinal cord acts in an autocrine or paracrine manner among the activated microglia and neurons, thus contributing to development of neuropathic pain.
登录
查看更多内容
影响因子：
5.4
作者：
GELBARD, HA;NOTTET, HSLM;GENDELMAN, HE
通讯作者：
GENDELMAN, HE
DOI：
10.1007/bf01978740
发表时间：
1981-01-01
期刊：
AGENTS AND ACTIONS
影响因子：
--
作者：
BONNET, J;LOISEAU, AM;BESSIN, P
通讯作者：
BESSIN, P
在缺乏血小板激活因子受体的小鼠中，对内毒素具有完整敏感性的过敏反应受损。
影响因子：
15.3
作者：
Ishii, S;Kuwaki, T;Nagase, T;Maki, K;Tashiro, F;Sunaga, S;Cao, W H;Kume, K;Fukuchi, Y;Ikuta, K;Miyazaki, J;Kumada, M;Shimizu, T
通讯作者：
Shimizu, T
影响因子：
2.5
作者：
Kobayashi, Kimiko;Fukuoka, Tetsuo;Noguchi, Koichi
通讯作者：
Noguchi, Koichi
影响因子：
5.8
作者：
DALLOB, A;GUINDON, Y;GOLDENBERG, MM
通讯作者：
GOLDENBERG, MM