Spinal cord protein interacting with C kinase 1 is required for the maintenance of complete Freund's adjuvant-induced inflammatory pain but not for incision-induced post-operative pain.
Spinal cord protein interacting with C kinase 1 is required for the maintenance of complete Freund's adjuvant-induced inflammatory pain but not for incision-induced post-operative pain.
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DOI：
10.1016/j.pain.2010.07.017
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发表时间：
2010-10
期刊：
影响因子：
7.4
通讯作者：
Tao YX
中科院分区：
文献类型：
--
作者：
Atianjoh FE;Yaster M;Zhao X;Takamiya K;Xia J;Gauda EB;Huganir RL;Tao YX
与C激酶1相互作用的蛋白质（Protein interacting with C kinase 1，PICK1）是一种含PDZ的蛋白质，在中枢神经元中与AMPA受体（AMPAR）GluR2亚基和蛋白激酶Cα（protein kinase Cα，PKCα）结合。作为一种靶向和转运蛋白，将活化形式的PKCα呈递给突触GluR2，并参与神经系统中突触AMPAR的运输。因此，PICK1可能参与通过激活AMPAR触发的许多生理和病理过程。我们在这里报告说，PICK1基因敲除小鼠显示受损的机械和热疼痛的超敏反应，在完全弗氏佐剂（CFA）诱导的炎性疼痛的维护。通过鞘内注射PICK1反义寡脱氧核苷酸急性瞬时敲低脊髓PICK1也有类似的效果。与此相反，敲除和敲低脊髓PICK1不影响切口诱导的守卫疼痛行为或机械或热疼痛超敏反应。我们还发现PICK1在背角中高度表达，在那里它与GluR2和PKCα相互作用。将CFA注射到后爪中，但不注射到后爪切口中，增加了背角中PKCα介导的Ser880处的GluR2磷酸化和GluR2内化。当脊髓PICK1缺乏时，这些增加不存在。鉴于背角PKCα介导的GluR2丝氨酸880磷酸化和GluR2内化有助于维持CFA诱导的炎性疼痛，我们的研究结果表明，脊髓PICK1可能通过促进背角神经元中PKCα介导的GluR2磷酸化和内化，参与持续性炎性疼痛的维持，但不参与切口诱导的术后疼痛。
Protein interacting with C kinase 1 (PICK1) is a PDZ-containing protein that binds to AMPA receptor (AMPAR) GluR2 subunit and protein kinase Cα (PKCα) in the central neurons. It functions as a targeting and transport protein, presents the activated form of PKCα to synaptic GluR2, and participates in synaptic AMPAR trafficking in the nervous system. Thus, PICK1 might be involved in many physiological and pathological processes triggered via the activation of AMPARs. We report here that PICK1 knockout mice display impaired mechanical and thermal pain hypersensitivities during complete Freund's adjuvant (CFA)-induced inflammatory pain maintenance. Acute transient knockdown of spinal cord PICK1 through intrathecal injection of PICK1 antisense oligodeoxynucleotide had a similar effect. In contrast, knockout and knockdown of spinal cord PICK1 did not affect incision-induced guarding pain behaviors or mechanical or thermal pain hypersensitivities. We also found that PICK1 is highly expressed in dorsal horn, where it interacts with GluR2 and PKCα. Injection of CFA into a hind paw, but not a hind paw incision, increased PKCα-mediated GluR2 phosphorylation at Ser880 and GluR2 internalization in dorsal horn. These increases were absent when spinal cord PICK1 was deficient. Given that dorsal horn PKCα-mediated GluR2 phosphorylation at Ser880 and GluR2 internalization contribute to the maintenance of CFA-induced inflammatory pain, our findings suggest that spinal PICK1 may participate in the maintenance of persistent inflammatory pain, but not in incision-induced post-operative pain, through promoting PKCα-mediated GluR2 phosphorylation and internalization in dorsal horn neurons.
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影响因子：
3.3
作者：
Park JS;Yaster M;Guan X;Xu JT;Shih MH;Guan Y;Raja SN;Tao YX
通讯作者：
Tao YX
影响因子：
8.8
作者：
Tao YX
通讯作者：
Tao YX
影响因子：
7.4
作者：
Chu, YC;Guan, Y;Tao, YX
通讯作者：
Tao, YX
影响因子：
3.4
作者：
Katano, Tayo;Furue, Hidemasa;Ito, Seiji
通讯作者：
Ito, Seiji
影响因子：
16.2
作者：
Lu, W;Ziff, EB
通讯作者：
Ziff, EB