...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera
【24h】

Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera

机译：脊柱神经脊髓冷超敏反应的离子机制

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nM ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl} carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Na(v)1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Na(v)1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity.
机译：感冒超敏反应在一系列神经病中很明显，可引起矛盾的灼热感冒疼痛。已知Ciguatoxin中毒会引起由食用受污染的热带鱼引起的疼痛综合症，这种综合症可能持续数月，包括瘙痒和感冒异常性疼痛。目前尚无合适的治疗方法。这项研究首次检查了太平洋雪茄毒素2诱导的冷超敏反应的神经底物和分子成分。在非智商大鼠中制作了背角椎板V / VI宽动态范围神经元的电生理记录。向感受野皮下注射10 nM ciguatoxin-2，可增加对无害和有害冷却的神经元反应。此外，对低阈值但无害的点状机械刺激的神经元反应也增强了。短暂的受体电位褪黑素8（TRPM8的拮抗剂）6-（{2- [2-氟-6-（三氟甲基）苯氧基] -2-甲基丙基}氨基甲酰基）吡啶-3-羧酸并不能逆转所产生的冷超敏反应。 ）。与Na（v）1.8拮抗剂A803467共注射可完全防止机械性和冷性超敏反应，而瞬时受体电位锚蛋白1（TRPA1）拮抗剂A967079仅可防止对无害冷却的超敏反应，而部分可防止对有害冷却的超敏性。在幼稚大鼠中，单独的Nav1.8，TRPA1或TRPM8拮抗剂既无毒也无害，不会引起冷诱发的神经元反应。 Ciguatoxins可能会将冷敏感性传递给不敏感的Na（v）1.8 / TRPA1阳性初级传入亚群，这可能是ciguatera中报道的冷异常性疼痛的基础。这些数据扩展了对正常条件下中枢脊髓冷敏性的理解，以及这些离子通道在这种转化的雪加毒素诱导的超敏性大鼠模型中的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号