神经病理性疼痛是临床上常见的慢性痛，目前仍缺乏有效的治疗药物。申请者在前期工作中发现NAAA抑制剂通过调控内源性小分子脂质PEA的含量，激活PPARα受体产生显著的抗神经病理性疼痛的作用，该作用在NAAA基因敲除小鼠中得到进一步验证。同时，我们在小鼠脊髓组织中发现NAAA主要表达在活化的小胶质细胞中，且在SNI模型组中表达显著增高。因此，我们认为NAAA在神经病理性疼痛发生发展中对中枢免疫炎症的调控具有十分重要的作用。本课题我们将研究的科学问题是：NAAA调控小胶质细胞活化的中枢免疫炎症机制对神经病理性疼痛发生发展的作用。项目将研究以下内容：（1）神经病理性疼痛发生发展中脊髓NAAA在基因水平、蛋白水平表达的时空分布特征与小胶质细胞活化的关系；（2）脊髓NAAA-PEA-PPARα通路调控中枢敏化的免疫炎症机制。研究成果将为新型抗神经病理性疼痛药物的开发及应用提供理论依据。

Neuropathic pain is a chronic and pathological pain that is lacking effective treatment. Our recent studies have suggested that pharmacological inhibition of N-acylethanolamine acid amidase (NAAA) activity exerts profound analgesic effects on spared nerve injury mouse models. This anti-allodynia effect was also confirmed in a mouse model lacking NAAA gene. We also found that NAAA was also over-expressed in spinal cord after spared nerve induced neuropathic pain. Based on these results, we hypothesis that NAAA is involving in the neuropathic developing. In this project, by using behavioral and molecular biological approaches, we will investigate the role of NAAA in neuropathic pain which includes: (1) The mRNA and protein expression and distribution of NAAA in spinal cord of spared nerve injury mouse; (2) The effect of NAAA inhibitors in regulation of spinal microglial activation. This project will provide theory basis for novel drug discovery and neuropathic pain treatment.