Tandem pore-domain Halothane Inhibited K+ channel (THIK1) is a two-pore-domain potassium channel (K2P) present in dorsal root ganglia (DRG). We previously demonstrated that THIK1 mRNA levels in the DRG dropped ipsilaterally 1day after CFA-induced cutaneous inflammation (CFA1). In this study we aimed to identify the currently unknown DRG subpopulations expressing THIK1, and to investigate the relationship between the channel and both inflammatory and spontaneous pain in normal rats. Using a combination of immunohistochemistry, western blotting and behavioural tests, we found that all small neurons and large groups of medium and large DRG neurons express THIK1. Myelinated and unmyelinated fibers, nerve endings in the skin and lamina I and II of the spinal cord also express the channel. THIK1 staining co-localizes with IB4-binding and trkA suggesting that the channel is expressed by nociceptors. At CFA1, both cytoplasmic and edge (membrane-associated) THIK1 staining were significantly reduced only in small neurons ipsilaterally compared to normal. At 4days after inflammation (CFA4), edge THIK1 staining levels in small neurons decreased bilaterally compared to normal. Medium and large size DRG neurons showed no change in THIK1 expression either at CFA1 or CFA4. Ipsilateral (but not contralateral) mean %intensities of THIK1 in small neurons at CFA1 correlated strongly negatively with spontaneous foot lifting (SFL) duration (a marker of spontaneous pain). Thus, nociceptors express THIK1 that can be regulated by cutaneous inflammation. Finally, in vivo siRNA knockdown of THIK1 resulted in longer SFL duration than siRNA scramble-treated rats. Taken together our evidence suggests a potential involvement for THIK1 in pain processing following inflammation.

中文翻译：

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皮肤炎症调节小C样伤害感受器背根神经节神经元中THIK1的表达。

串联孔域氟烷抑制的K +通道（THIK1）是背根神经节（DRG）中存在的两孔域钾通道（K2P）。我们先前证明，CFA诱发的皮肤炎症（CFA1）后1天，DRG中的THIK1 mRNA水平下降。在这项研究中，我们旨在确定目前未知的表达THIK1的DRG亚群，并研究正常大鼠中通道与炎性和自发性疼痛之间的关系。使用免疫组织化学，免疫印迹和行为测试的组合，我们发现所有小神经元和大中型和大型DRG神经元组都表达THIK1。有髓和无髓纤维，皮肤的神经末梢以及脊髓的I和II层也表达该通道。THIK1染色与IB4结合和trkA共定位，表明该通道由伤害感受器表达。在CFA1，仅同侧的小神经元与正常相比，胞浆和边缘（膜相关）THIK1染色均显着降低。炎症后4天（CFA4），与正常相比，小神经元的边缘THIK1染色水平双侧降低。中型和大型DRG神经元在CFA1或CFA4处的THIK1表达均无变化。同侧（但非对侧）的平均CFA1小神经元THIK1强度百分比与自发足部抬高（SFL）持续时间（自发性疼痛的标志）密切相关。因此，伤害感受器表达可通过皮肤炎症调节的THIK1。最后，THIK1的体内siRNA敲除导致的SFL持续时间比siRNA加扰处理的大鼠更长。综上所述，我们的证据表明THIK1可能与炎症后的疼痛处理有关。