The Role And Mechanism Of S1PR2 On The Neuropathic Pain Induced By Partial Sciatic Nerve Ligation

Aim:Sphingosine 1-phosphate receptor 2(S1PR2)is belonged to the seven transmembrane G protein coupled receptor family,which can be activated by its natural ligand sphingosine 1-phosphate(S1P)to initiate the signal transduction and involved in a wide range of biological effects.It is showed that,S1PR2 can modulate the migration of immune cells,the vascular permeability and mediate the change of neuronal plasticity.We guess that it may impact the neuropathic pain.In this research,the effects of S1PR2 on the development of the neuropathic pain were studied from the animal model,cell and molecular level.Method:We built the neuropathic pain model induced by partial sciatic nerve ligation(pSNL)and measured S1PR2 expression on both the injured sciatic nerve and lumbar enlargement.The impact of S1PR2-deficency on the physiological pain threshold was detected;further,we measured the 50%paw withdrawal threshold of wild-type group and S1PR2-deficiency group along the time post surgery.According to the change of pain threshold,we focused on the differences of inflammatory factor(TNF-α、IL-6、IL-1β and so on)with the real-time quantitative PCR(RT-PCR)between two groups.The injured sciatic nerve’s neutrophil infiltration and glial cell’s activation in the spine were detected with immunofluorescence.Matrix metalloproteinase 9(MMP9)was measured with RT-PCR and the western blot.Both MMP9 and IL-1β were localized with the immunofluorescence.And MMP9,s substrate myelin basic protein(MBP)was checked with the western blot and immunofluorescence.Result:In the neuropathic pain model of wild-type mice,S1PR2 expression showed the decreasing trend with the change of pain threshold.S1PR2-deficiency did not influence the pain sensitivity in physiological condition.At 3 days post the operation,S1PR2-deficiency group showed reduced 50%paw withdrawal threshold compared with wild-type mice(P<0.05).In the ligated sciatic nerve,the mRNA expression of IL-1β was increased;the number of neutrophil infiltration and activated astrocytes was also increased.The MMP9 expression was elevated and had the co-localization with neutrophil and IL-1β.The expression of myelin basic protein was decreased.Conclusion:S1PR2-deficency could increase the pain sensitivity of the mice with the neuropathic pain model and promote the development of the neuropathic pain.