摘要
Orexins/Hypocretins是下丘脑生成的兴奋性神经肽,分为OrexinA和OrexinB两种。近年来发现其在痛觉感受和调制中发挥重要角色。Orexin的受体OX1R和OX2R在痛觉下行抑制系统各水平广泛表达是参与痛觉调制的解剖学基础。行为学研究显示,脊髓及脊髓上水平注射Orexins对炎性痛、切口痛、神经痛等模型有不同程度的镇痛效应。中枢神经系统Orexin作用于神经元主要引起兴奋性效应;Orexin作用于中脑导水管灰质腹外侧区神经元突触后膜受体,引起大麻素2-AG释放并逆向传递至突触前膜,通过大麻素受体1抑制γ氨基丁酸(γ-aminobutyric acid,GABA)释放而实现镇痛效应。研究还发现Orexin与强啡肽、内源性大麻素、谷氨酸、GABA等多种神经递质共存也可能是其镇痛效应的物质基础。总之,Orexin可能是一种新的镇痛靶点。
Orexins/Hypocretins are excitatory neuropeptides produced by hypothalamus rieurons,including OrexinA and OrexinB.Recent studies revealed their important role in pain perception and modulation.Orexin receptors,OX1R and OX2R,are widely expressed in pain descending inhibitory pathways,which provides anatomical basis for its involvement in pain modulation.Behavior studies show that spinal and supraspinal injection of Orexins produce analgesic effect in models of inflammatory pain,incisional pain and neuropathic pain.Orexin of central nervous system mainly exerts excitatory effect on neurons.For neuron postsynaptic receptors in ventrolateral periaqueductal gray matter （vPAG）,orexin produces analgesic effect by causing cannabinoid release and binding to pre-synaptic cannabinoid receptor 1 that inhibits （γ-aminobutyric acid,GABA） release.In addition,orexin co-expressed with neurotransmitters such as dynorphin,endogenerous cannabinoid,glutamine and GABA.Thus orexins might be a potential target for pain therapies.
出处
《复旦学报（医学版）》
CAS
CSCD
北大核心
2015年第3期413-417,共5页
Fudan University Journal of Medical Sciences
基金
国家自然科学基金青年项目(81403472)
上海中医药大学预算内项目(2013JW55)~~
