Extracellular signal-regulated kinase (ERK) activation is required for itch sensation in the spinal cord.
Extracellular signal-regulated kinase (ERK) activation is required for itch sensation in the spinal cord.
复制标题
脊髓瘙痒感需要细胞外信号调节激酶 (ERK) 激活
DOI：
10.1186/1756-6606-7-25
复制
发表时间：
2014-04-03
期刊：
影响因子：
3.6
通讯作者：
Ding YQ
中科院分区：
文献类型：
--
作者：
Zhang L;Jiang GY;Song NJ;Huang Y;Chen JY;Wang QX;Ding YQ
瘙痒，特别是慢性瘙痒，会对个体的生活质量产生显著的负面影响。然而，中枢神经系统中瘙痒处理的分子机制仍然很大程度上未知。我们在这里报告说，激活ERK信号在脊髓所需的瘙痒感觉。如通过抗磷酸化ERK 1/2免疫染色所揭示的，在皮内注射组胺和化合物48/80而不是氯喹或SLIGRL-NH 2处理的小鼠的脊髓背角中观察到ERK活化，表明ERK活化仅发生在组胺依赖性急性瘙痒中。此外，在2，4-二硝基氟苯（DNFB）诱导的瘙痒中也观察到ERK激活。因此，鞘内注射ERK磷酸化抑制剂U 0126可显著降低组胺和DNFB诱导的小鼠抓挠行为，但对氯喹诱导的抓挠行为无影响。此外，组胺H1受体拮抗剂扑尔敏可降低组胺诱导的抓挠行为和ERK激活，但对DNFB诱导的瘙痒反应无影响。最后，膜片钳记录表明，在组胺，氯喹和DNFB处理的小鼠的背角神经元的自发兴奋性突触后电流（sEPSC）的增加，并在很大程度上阻止了组胺和DNFB处理的小鼠，而不是用氯喹处理的小鼠洗澡的U 0126动作电位阈值的降低。我们的研究结果表明，在脊髓水平的瘙痒感ERK激活的关键作用。
Itch, chronic itch in particular, can have a significant negative impact on an individual’s quality of life. However, the molecular mechanisms underlying itch processing in the central nervous system remain largely unknown. We report here that activation of ERK signaling in the spinal cord is required for itch sensation. ERK activation, as revealed by anti-phosphorylated ERK1/2 immunostaining, is observed in the spinal dorsal horn of mice treated with intradermal injections of histamine and compound 48/80 but not chloroquine or SLIGRL-NH2, indicating that ERK activation only occurs in histamine-dependent acute itch. In addition, ERK activation is also observed in 2, 4-dinitrofluorobenzene (DNFB)-induced itch. Consistently, intrathecal administration of the ERK phosphorylation inhibitor U0126 dramatically reduces the scratching behaviors induced by histamine and DNFB, but not by chloroquine. Furthermore, administration of the histamine receptor H1 antagonist chlorpheniramine decreases the scratching behaviors and ERK activation induced by histamine, but has no effect on DNFB-induced itch responses. Finally, the patch-clamp recording shows that in histamine-, chloroquine- and DNFB-treated mice the spontaneous excitatory postsynaptic current (sEPSC) of dorsal horn neurons is increased, and the decrease of action potential threshold is largely prevented by bathing of U0126 in histamine- and DNFB-treated mice but not those treated with chloroquine. Our results demonstrate a critical role for ERK activation in itch sensation at the spinal level.
登录
查看更多内容
影响因子：
25
作者：
Ji, RR;Baba, H;Woolf, CJ
通讯作者：
Woolf, CJ
影响因子：
82.9
作者：
Kawasaki, Yasuhiko;Xu, Zhen-Zhong;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong
影响因子：
5.3
作者：
Davidson, Steve;Zhang, Xijing;Giesler, Glenn J., Jr.
通讯作者：
Giesler, Glenn J., Jr.
影响因子：
4.8
作者：
Favata, MF;Horiuchi, KY;Trzaskos, JM
通讯作者：
Trzaskos, JM
影响因子：
15.9
作者：
Liu, Tong;Berta, Temugin;Ji, Ru-Rong
通讯作者：
Ji, Ru-Rong