Sphingosine lysolipids in the CNS: endogenous cannabinoid antagonists or a parallel pain modulatory system?
Sphingosine lysolipids in the CNS: endogenous cannabinoid antagonists or a parallel pain modulatory system?
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DOI：
10.1016/j.lfs.2013.06.004
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发表时间：
2013-08-14
期刊：
影响因子：
6.1
通讯作者：
Sim-Selley, Laura J.
中科院分区：
文献类型：
--
作者：
Selley, Dana E.;Welch, Sandra P.;Sim-Selley, Laura J.
大量患者经历慢性疼痛和目前处方的止痛药的难治性副作用。最近的证据表明，由内源性脂质配体激活的两类G蛋白偶联受体，即内源性大麻素（eCB）和鞘氨醇-1-磷酸（S1 P）受体，在免疫和神经系统中广泛表达，具有重要的疼痛调节作用。在中枢神经系统（CNS）中，CB 1大麻素和S1 P1受体表达最丰富，并表现出重叠的解剖分布和相似的信号传导机制。eCB系统已成为治疗慢性疼痛的潜在靶点，但对S1 P在疼痛调节中的作用知之甚少。eCB和S1 P系统都通过中枢和外周神经系统调节疼痛感知。在大多数研究范式中，eCB系统主要抑制疼痛感知。相反，S1 P在外周作用于S1 P1和S1 P3受体可以增强对各种疼痛刺激的敏感性或引起自发性疼痛。然而，S1 P作用于S1 P1受体和CNS中可能的其他靶点可以减弱对各种疼痛刺激的敏感性。有趣的是，其他内源性鞘脂衍生物可能在中枢疼痛敏化中发挥作用。此外，这些鞘脂也可以作为CB 1大麻素受体拮抗剂，但这种相互作用的生理相关性是未知的。总的来说，eCB和鞘脂系统都为治疗慢性疼痛提供了有希望的靶点。本综述比较和对比了eCB和S1 P系统，重点是它们在疼痛调节中的作用，并考虑了这些系统之间可能的相互作用点。
A significant number of patients experience chronic pain and the intractable side effects of currently prescribed pain medications. Recent evidence indicates important pain modulatory roles for two classes of G-protein-coupled receptors that are activated by endogenous lipid ligands, the endocannabinoid (eCB) and sphingosine-1-phosphate (S1P) receptors, which are widely expressed in both the immune and nervous systems. In the central nervous system (CNS), CB1 cannabinoid and S1P1 receptors are most abundantly expressed and exhibit overlapping anatomical distributions and similar signaling mechanisms. The eCB system has emerged as a potential target for treatment of chronic pain, but comparatively little is known about the roles of S1P in pain regulation. Both eCB and S1P systems modulate pain perception via the central and peripheral nervous systems. In most paradigms studied, the eCB system mainly inhibits pain perception. In contrast, S1P acting peripherally at S1P1 and S1P3 receptors can enhance sensitivity to various pain stimuli or elicit spontaneous pain. However, S1P acting at S1P1 receptors and possibly other targets in the CNS can attenuate sensitivity to various pain stimuli. Interestingly, other endogenous sphingolipid derivatives might play a role in central pain sensitization. Moreover, these sphingolipids can also act as CB1 cannabinoid receptor antagonists, but the physiological relevance of this interaction is unknown. Overall, both eCB and sphingolipid systems offer promising targets for the treatment of chronic pain. This review compares and contrasts the eCB and S1P systems with a focus on their roles in pain modulation, and considers possible points of interaction between these systems.
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影响因子：
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作者：
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