Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats.
Contribution of TRESK two-pore domain potassium channel to bone cancer-induced spontaneous pain and evoked cutaneous pain in rats.
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DOI：
10.1177/17448069211023230
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发表时间：
2021-01
期刊：
影响因子：
3.3
通讯作者：
Xing GG
中科院分区：
文献类型：
--
作者：
Liu JP;Jing HB;Xi K;Zhang ZX;Jin ZR;Cai SQ;Tian Y;Cai J;Xing GG
癌症相关的疼痛使人衰弱。然而，癌症引起的自发性疼痛和诱发性疼痛的机制仍不清楚。在这里，使用 TRESK 方法的免疫荧光染色、过表达和敲低行为测试，我们发现 TRESK 钾通道广泛分布在大鼠后爪皮肤的 CGRP+ 和 IB4+ 神经纤维、缺乏 IB4+ 纤维神经支配的胫骨骨膜中的 CGRP+ 神经纤维以及大鼠的 CGRP+ 和 IB4+ 背根神经节 (DRG) 神经元上。此外，我们发现骨癌大鼠后爪皮肤、胫骨骨膜和 DRG 神经元内相应神经纤维中 TRESK 的表达降低。 DRG 神经元中 TRESK 的过度表达可减轻荷瘤大鼠中癌症诱发的自发性疼痛（部分反映骨骼痛）和诱发性疼痛（反映皮肤痛），其中诱发性疼痛的缓解比自发性疼痛延迟。相比之下，DRG 神经元中 TRESK 的敲低既会产生自发性疼痛，也会在幼稚大鼠中引起诱发疼痛。这些结果表明，由于胫骨骨膜内缺乏IB4+纤维神经支配，TRESK在骨膜和皮肤中的差异分布和表达减少可能导致骨癌大鼠中癌症诱发的自发痛和诱发痛的行为差异。因此，在动物模型中评估某些新型镇痛药的效果时，应同时完成自发痛和诱发痛的评估。此外，这项研究还为外周 TRESK 在癌症引起的自发性疼痛和诱发皮肤疼痛中的作用提供了坚实的证据。
Cancer-associated pain is debilitating. However, the mechanism underlying cancer-induced spontaneous pain and evoked pain remains unclear. Here, using behavioral tests with immunofluorescent staining, overexpression, and knockdown of TRESK methods, we found an extensive distribution of TRESK potassium channel on both CGRP+ and IB4+ nerve fibers in the hindpaw skin, on CGRP+ nerve fibers in the tibial periosteum which lacks IB4+ fibers innervation, and on CGRP+ and IB4+ dorsal root ganglion (DRG) neurons in rats. Moreover, we found a decreased expression of TRESK in the corresponding nerve fibers within the hindpaw skin, the tibial periosteum and the DRG neurons in bone cancer rats. Overexpression of TRESK in DRG neurons attenuated both cancer-induced spontaneous pain (partly reflect skeletal pain) and evoked pain (reflect cutaneous pain) in tumor-bearing rats, in which the relief of evoked pain is time delayed than spontaneous pain. In contrast, knockdown of TRESK in DRG neurons produced both spontaneous pain and evoked pain in naïve rats. These results suggested that the differential distribution and decreased expression of TRESK in the periosteum and skin, which is attributed to the lack of IB4+ fibers innervation within the periosteum of the tibia, probably contribute to the behavioral divergence of cancer-induced spontaneous pain and evoked pain in bone cancer rats. Thus, the assessment of spontaneous pain and evoked pain should be accomplished simultaneously when evaluating the effect of some novel analgesics in animal models. Also, this study provides solid evidence for the role of peripheral TRESK in both cancer-induced spontaneous pain and evoked cutaneous pain.
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影响因子：
3.1
作者：
Andresen, Trine;Pfeiffer-Jensen, Mogens;Arendt-Nielsen, Lars
通讯作者：
Arendt-Nielsen, Lars
影响因子：
7.4
作者：
Guedon JG;Longo G;Majuta LA;Thomspon ML;Fealk MN;Mantyh PW
通讯作者：
Mantyh PW
影响因子：
7.4
作者：
Jimenez-Andrade, Juan M.;Martin, Carl D.;Mantyh, Patrick W.
通讯作者：
Mantyh, Patrick W.
影响因子：
5.5
作者：
Kang, Dawon;Kim, Donghee
通讯作者：
Kim, Donghee
DOI：
10.1177/0333102417720216
发表时间：
2018-04
期刊：
Cephalalgia : an international journal of headache
影响因子：
--
作者：
LaPaglia DM;Sapio MR;Burbelo PD;Thierry-Mieg J;Thierry-Mieg D;Raithel SJ;Ramsden CE;Iadarola MJ;Mannes AJ
通讯作者：
Mannes AJ