我们以往的工作表明，外周神经损伤在引起神经病理性疼痛的同时也上调脊髓背角TSPO，促进疼痛恢复。本项目的预实验发现，部分坐骨神经损伤（SNI）上调脊髓背角肝X受体（LXR）α/β，LXRs激动剂可抑制SNI引起的触诱发痛,提示LXRs可能也有促进疼痛恢复的作用，但机制不清。研究表明，LXRs激动剂可促进神经甾体合成，而神经甾体可抑制致炎细胞因子表达。我们以往的工作表明，TNF-α通过提高脊髓背角突触传递效率，放大痛信号。本项目拟明确何种LXR亚型在神经病理性疼痛中起作用，观察LXRs是否通过促进脊髓背角神经甾体合成而抑制致炎细胞因子表达，探讨LXRs是否改变背角投射神经元的突触结构和功能，最后研究外周神经损伤后脊髓背角LXRs的上调是否由TLR2/4介导。由此探讨SNI后脊髓背角由"TLR2/4→LXRs→神经甾体→致炎细胞因子"所介导的调节神经元结构和功能以促进神经病理性疼痛恢复的机制。

Our previous work has shown that peripheral nerve injury upregulates TSPO in the spinal dorsal horn when it induces neuropathic pain, which promotes recovery from neuropathic pain. Our recent studies showed that spared nerve injury (SNI) induced the upregulation of LXRα/β, and that LXRs agonist decreased SNI-induced mechanical allodynia, suggesting that LXRs may promote recovery from neuropathic pain,but the exact mechanisms are still unclear.Previous studies have demonstrated that LXR agonist can promote the synthesis of neuroactive steroids, whereas neuroactive steroids can inhibit the release of inflammatory cytokines. Our previous work has shown that overexpression of TNF-α contributs to neuropathic pain by enhancement of synaptic transmission in spinal dorsal horn. In the present study, we will determine which subtype of LXRs play a role in neuropathic pain. Next, we will examine whether LXRs can inhibit the release of cytokines in the spinal dorsal horn and examine whether neuroactive steroids play roles in this process. Meanwhile we will investigate whether LXRs affect the morphosis and function of spinal dorsal horn neurons. Whether TLR2/4 lead to the upregulation of LXRs will also be investigated. Thus we will elucidate the mechanisms that LXRs promote recovery from neuropathic pain by modulating the morphosis and function of neurons, and serve to develop new analgesics.