SOCS3在病理性疼痛中的作用

The Role of SOCS3 in the Pathologic Pain

细胞因子信号传导抑制因子3(SOCS3)是细胞因子信号传导抑制因子蛋白质家族(SOCS)的一员。SOCS3是一种重要的细胞内蛋白质,在体内负调控细胞因子介导的信号通路,参与机体免疫、生长、造血、新陈代谢及肿瘤增殖等各种关键过程。近年的研究发现,SOCS3参与疼痛的调控,在神经病理性疼痛、炎性疼痛等多种类型疼痛及吗啡耐受中发生表达的变化。在坐骨神经慢性压迫损伤(CCI)模型中,磷酸二聚化的STAT3转移到细胞核内诱导脊髓背角SOCS3表达增加,在完全弗氏佐剂(CFA)炎性疼痛大鼠中,下丘脑室旁核(PVN)内SOCS3在急性期蛋白质表达水平增加、其慢性期表达下降,在骨癌疼痛大鼠腰2~5背根神经节(DRG)中SOCS3蛋白质水平显著下降。鞘内注射SOCS3慢病毒载体、阿司匹林触发的脂蛋白A4(ATL)和芍药苷,或通过抑制非编码RNA表达降低非编码RNA对SOCS3的抑制作用,能够增加SOCS3表达发挥镇痛作用。SOCS3通过抑制Janus激酶/信号转导子和转录激活子3(JAK/STAT3)信号通路及下游基因的表达,阻碍白细胞介素-1(IL-1)、IL-6和肿瘤坏死因子α(TNF-α)等多种炎性因子的分泌,以及核因子κB(NF-κB)的激活和转移等,发挥抗炎和镇痛作用。本文主要对SOCS3缓解疼痛的可能机制进行综述,探讨SOCS3在病理性疼痛中的作用。

Suppressor of cytokine signaling 3(SOCS3)is a member of the suppressor of cytokine signaling protein family(SOCS).SOCS3 is an important protein in cells that negatively regulates the signaling pathway mediated by cytokine in vivo and involves in a variety of key processes in the body including immune,growth,hematopoietic,metabolic processes and the proliferation of tumors.In recent years,it has been found that SOCS3 was involved in the regulation of pain.Changes in SOCS3 expression have been found in neuropathic pain,inflammatory pain and other types of pain as well as morphine tolerance.In the chronic constriction injury(CCI)model,the translocation of the phosphorylated and dimerized STAT3 into the nucleus induced increasing SOCS3 expression in spinal dorsal horn.In rats with complete Freund’s adjuvant(CFA)-induced inflammatory pain,the expression of SOCS3 in the hypothalamic paraventricular nucleus(PVN)was increased in the acute phase and decreased in the chronic phase.The level of SOCS3 in the dorsal root ganglia(DRG)of the ipsilateral dorsal 2-5 was significantly decreased in the bone cancer pain model rats.Intravaginal injection of SOCS3 lentiviral vectors,or Aspirin-triggered Lipoxin A4(ATL),or paeoniflorin,or inhibition of non-coding RNA which decreases the inhibition of non-coding RNA on SOCS3,all increases SOCS3 expression to play an analgesic role.SOCS3 has anti-inflammatory and analgesic effects through inhibiting Janus kinase/signal transducer and activator of transcription 3(JAK/STAT3)signaling pathway and the expression of downstream genes,through inhibiting the secretion of interleukin-1(IL-1),IL-6,tumour necrosis factor-α(TNF-α)and other inflammatory factors,through inhibiting the activation and transfer of nuclear factor kappa-B(NF-κB)and so on.This article mainly reviews the possible mechanisms of SOCS3 in relieving pain and discussing the role of SOCS3 in pathologic pain.