Genetic evidence for involvement of neuronally expressed S1P₁ receptor in nociceptor sensitization and inflammatory pain.
Genetic evidence for involvement of neuronally expressed S1P₁ receptor in nociceptor sensitization and inflammatory pain.
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DOI：
10.1371/journal.pone.0017268
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发表时间：
2011-02-17
期刊：
影响因子：
3.7
通讯作者：
Haberberger RV
中科院分区：
文献类型：
--
作者：
Mair N;Benetti C;Andratsch M;Leitner MG;Constantin CE;Camprubí-Robles M;Quarta S;Biasio W;Kuner R;Gibbins IL;Kress M;Haberberger RV
鞘氨醇-1-磷酸（S1 P）是免疫应答的关键调节剂。免疫细胞、上皮细胞和血细胞在发炎组织中产生高水平的S1 P。然而，目前尚不清楚S1 P是否作用于伤害性神经元的末梢，从而促进炎性疼痛的产生。我们发现S1 P的S1 P1受体在感觉神经元包括伤害感受器的亚群中表达。S1 P和S1 P1受体激动剂在体外和体内均诱导对有害热刺激的超敏反应。在缺乏TRPV 1通道的小鼠中，S1 P诱导的超敏反应强烈减弱。S1 P和炎症诱导的超敏反应显着降低了小鼠的条件性伤害感受器特异性缺失的S1 P1受体。我们的数据表明，神经元表达的S1 P1受体在调节伤害感受器功能中起着重要作用，并且S1 P/S1 P1信号传导可能是与炎症相关的热超敏反应和痛觉过敏发作的关键参与者。
Sphingosine-1-phosphate (S1P) is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P1 receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P1 receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P1 receptor. Our data show that neuronally expressed S1P1 receptors play a significant role in regulating nociceptor function and that S1P/S1P1 signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation.
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影响因子：
20.3
作者：
Allende, ML;Yamashita, T;Proia, RL
通讯作者：
Proia, RL
影响因子：
3.6
作者：
Deng, Qiaolin;Clemas, Joseph A.;Parent, Stephen A.
通讯作者：
Parent, Stephen A.
影响因子：
3
作者：
FORSTER, C;HANDWERKER, HO
通讯作者：
HANDWERKER, HO
影响因子：
7.4
作者：
Breese, NM;George, AC;Stucky, CL
通讯作者：
Stucky, CL
DOI：
10.1073/pnas.0901507106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cavanaugh, Daniel J.;Lee, Hyosang;Anderson, David J.
通讯作者：
Anderson, David J.