S1P-S1PRs Alliance in Neuropathic Pain Processing

Jin-Chao Hou , Xiang-Ming Fang
Department of Anesthesiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
J Anesth Perioper Med 2015; 2(2): 87- 95 . Published on Mar 31, 2015 . doi:10.24015/JAPM.2015.0013
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Aim of review: Neuropathic pain (NPP), a common clinical condition, is characterized by allodynia and hyperalgesia. In the setting of NPP, components in the peripheral and central transmission pathway of pain exhibit tremendous plasticity, facilitating pain signal conduction and giving rise to hypersensitivity. Clarifying the signal path of nociceptive processing and discovering the key molecules involved in NPP may allow improvement of its treatment.

Method: This article reviewed the sphingosine-1-phosphate (S1P) and sphingosine-1-phosphate receptors (S1PRs) alliance that initiates and maintains peripheral and central sensitization in NPP, underlying the fundamental contribution and multiple mechanisms of this alliance in synaptic plasticity.

Recent findings: In the peripheral nervous system, S1P-S1PRs alliance contributes to the inflammatory chemical milieu formation and ion channel function, which increase the ectopic action potentials of sensory neurons. In addition, S1P-S1PRs alliance affects thermal hyperalgesia through enhancing inward tetrodotoxin-resistant INa+ and decreasing total outward IK+ on the nociceptors. In the central nervous system, S1P-S1PRs alliance facilitates the neuroinflammatory response and glutamate accumulation at the "first pain synapse", which leads to persistent central hypersensitization. Furthermore, S1P-S1PRs alliance could disequilibrate the extracellular glutamate via reducing the activities of glutamine synthetase (GS) and glutamate transporters (GTs), which are the key players in glutamate metabolism.

Summary: Targeting S1P-S1PRs alliance may be an "Achilles' heel" of the "Trojan horse" model of NPP.



Citation: Jin-Chao Hou, Xiang-Ming Fang. S1P-S1PRs alliance in neuropathic pain processing. J Anesth Perioper Med 2015; 2: 87-95. doi: 10.24015/JAPM.2015.0013

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