Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.
Synthesis of lipid mediators during UVB-induced inflammatory hyperalgesia in rats and mice.
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DOI：
10.1371/journal.pone.0081228
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Scholich K
中科院分区：
文献类型：
--
作者：
Sisignano M;Angioni C;Ferreiros N;Schuh CD;Suo J;Schreiber Y;Dawes JM;Antunes-Martins A;Bennett DL;McMahon SB;Geisslinger G;Scholich K
炎性疼痛期间的外周敏化由多种内源性促痛觉介质介导，包括许多氧化脂质，其中一些用作感觉TRP通道的内源性调节剂。这些脂质是花生四烯酸和亚油酸途径的类花生酸，以及溶血磷脂酸（LPAs）。然而，它们在炎性疼痛过程中的调节模式及其对外周致敏的贡献仍不清楚。在这里，我们使用UVB模型的炎症疼痛，以调查炎症部位的脂质浓度的变化，背根神经节（DRG）以及脊髓背角和量化的21个脂质种类从5个不同的脂质家族在炎症高峰期照射后48小时。我们发现，已知的促炎脂质以及在炎性疼痛中具有未知作用的脂质在皮肤中强烈增加，而令人惊讶的是，在DRG或背角中观察到脂质水平的变化很小。重要的是，虽然小鼠和大鼠之间的细胞色素（CYP）基因的数量有很大的差异，但CYP衍生的脂质在两个物种中的调节相似。由于TRPV 1激动剂LPA 18∶1、9-HODE和13-HODE、5-HETE和12-HETE在皮肤中升高，它们可能在UVB诱导的炎性疼痛中参与热痛觉过敏和机械性异常性疼痛。这些结果可能解释了为什么一些研究显示环氧合酶抑制剂对UVB诱导的皮肤炎症的镇痛作用相对较弱，因为它们不抑制其他促痛脂质如LPA 18∶1，9-和13-HODE和HETE的合成。
Peripheral sensitization during inflammatory pain is mediated by a variety of endogenous proalgesic mediators including a number of oxidized lipids, some of which serve endogenous modulators of sensory TRP-channels. These lipids are eicosanoids of the arachidonic acid and linoleic acid pathway, as well as lysophophatidic acids (LPAs). However, their regulation pattern during inflammatory pain and their contribution to peripheral sensitization is still unclear. Here, we used the UVB-model for inflammatory pain to investigate alterations of lipid concentrations at the site of inflammation, the dorsal root ganglia (DRGs) as well as the spinal dorsal horn and quantified 21 lipid species from five different lipid families at the peak of inflammation 48 hours post irradiation. We found that known proinflammatory lipids as well as lipids with unknown roles in inflammatory pain to be strongly increased in the skin, whereas surprisingly little changes of lipid levels were seen in DRGs or the dorsal horn. Importantly, although there are profound differences between the number of cytochrome (CYP) genes between mice and rats, CYP-derived lipids were regulated similarly in both species. Since TRPV1 agonists such as LPA 18∶1, 9- and 13-HODE, 5- and 12-HETE were elevated in the skin, they may contribute to thermal hyperalgesia and mechanical allodynia during UVB-induced inflammatory pain. These results may explain why some studies show relatively weak analgesic effects of cyclooxygenase inhibitors in UVB-induced skin inflammation, as they do not inhibit synthesis of other proalgesic lipids such as LPA 18∶1, 9-and 13-HODE and HETEs.
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影响因子：
17.1
作者：
Dawes JM;Calvo M;Perkins JR;Paterson KJ;Kiesewetter H;Hobbs C;Kaan TK;Orengo C;Bennett DL;McMahon SB
通讯作者：
McMahon SB
影响因子：
15.9
作者：
Patwardhan, Amol M.;Akopian, Armen N.;Hargreaves, Kenneth M.
通讯作者：
Hargreaves, Kenneth M.
DOI：
10.1038/nrd2757
发表时间：
2009-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
62.1
作者：
Blaho, Victoria A.;Hla, Timothy
通讯作者：
Hla, Timothy
影响因子：
7.4
作者：
Bishop, Thomas;Marchand, Fabien;McMahon, Stephen B.
通讯作者：
McMahon, Stephen B.