Acidosis counteracts itch tachyphylaxis to consecutive pruritogen exposure dependent on acid-sensing ion channel 3

作者：Jiang, Yi-Ming; Huang, Chen; Peng, Zhong; Han, Shao-Ling; Li, Wei-Guang; Zhu, Michael Xi; Xu, Tian-Le^*

来源：Molecular Pain, 2017, 13: 1744806917721114.

DOI：10.1177/1744806917721114

• Tachyphylaxis
• chronic itch
• acidosis
• SL-NH2
• acid-sensing ion channel 3
• Mas-related G-protein-coupled receptor C11

Tachyphylaxis of itch refers to a markedly reduced scratching response to consecutive exposures of a pruritogen, a process thought to protect against tissue damage by incessant scratching and to become disrupted in chronic itch. Here, we report that a strong stimulation of the Mas-related G-protein-coupled receptor C11 by its agonist, Ser-Leu-Ile-Gly-Arg-Leu-NH2 (SL-NH2) or bovine adrenal medulla 8-22 peptide, via subcutaneous injection in mice induces tachyphylaxis to the subsequent application of SL-NH2 to the same site. Notably, co-application of acid and SL-NH2 following the initial injection of the pruritogen alone counteracted itch tachyphylaxis by augmenting the scratching behaviors in wild-type but not in acid-sensing ion channel 3-null, animals. Using an activity-dependent silencing strategy, we identified that acid-sensing ion channel 3-mediated itch enhancement mainly occurred via the Mas-related G-protein-coupled receptor C11-responsive sensory neurons. Together, our results indicate that acid-sensing ion channel 3, activated by concomitant acid and certain pruritogens, constitute a novel signaling pathway that counteracts itch tachyphylaxis to successive pruritogenic stimulation, which likely contributes to chronic itch associated with tissue acidosis.

• 出版日期2017-7-26
• 单位上海交通大学