Duric V, McCarson K E
Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Mail Stop 1018, Kansas City, KS 66160, USA.
Neuroscience. 2005;133(4):999-1006. doi: 10.1016/j.neuroscience.2005.04.002.
Acute or chronic stress can alter hippocampal structure, cause neuronal damage, and decrease hippocampal levels of the neurotrophin brain-derived neurotrophic factor (BDNF). The tachykinin substance P and its neurokinin-1 (NK-1) receptor may play a critical role in neuronal systems that process nociceptive stimuli; their importance in stress-activated systems has recently been demonstrated by the antidepressant-like actions of NK-1 receptor antagonists. However, the functional similarities between neurokinin receptors in the hippocampus and those in sensory systems are poorly understood, as is the significance of hippocampal NK-1 receptor in the context of chronic pain. Therefore, we investigated the effects of immobilization stress or inflammatory stimuli on NK-1 receptor and BDNF gene expression in the rat hippocampus. Rats received an acute or chronic immobilization stress, or an acute (formalin) or chronic (complete Freund's adjuvant) inflammatory stimulus to the right hind paw. Subsequently hippocampal volume and specific gravity were measured and NK-1 receptor and BDNF mRNA levels quantified using ribonuclease protection assays. Results showed that either stress or pain down-regulates expression of both NK-1 receptor and BDNF genes in the hippocampus. Hippocampal volume was increased by either pain or stress; this may be due to edema (decreased specific gravity). Thus, BDNF and NK-1 receptor gene plasticity may reflect sensory activation or responses to neuronal injury. These data may provide useful markers of hippocampal activation during chronic pain, and suggest similarities in the mechanisms underlying chronic pain and depression.
急性或慢性应激可改变海马结构，导致神经元损伤，并降低海马中神经营养因子脑源性神经营养因子（BDNF）的水平。速激肽P物质及其神经激肽-1（NK-1）受体可能在处理伤害性刺激的神经元系统中起关键作用；NK-1受体拮抗剂的抗抑郁样作用最近证明了它们在应激激活系统中的重要性。然而，海马中的神经激肽受体与感觉系统中的神经激肽受体之间的功能相似性了解甚少，慢性疼痛背景下海马NK-1受体的意义也不清楚。因此，我们研究了束缚应激或炎症刺激对大鼠海马中NK-1受体和BDNF基因表达的影响。大鼠接受急性或慢性束缚应激，或右后爪的急性（福尔马林）或慢性（完全弗氏佐剂）炎症刺激。随后测量海马体积和比重，并使用核糖核酸酶保护试验定量NK-1受体和BDNF mRNA水平。结果表明，应激或疼痛均下调海马中NK-1受体和BDNF基因的表达。疼痛或应激均可增加海马体积；这可能是由于水肿（比重降低）所致。因此，BDNF和NK-1受体基因可塑性可能反映感觉激活或对神经元损伤的反应。这些数据可能为慢性疼痛期间海马激活提供有用的标志物，并提示慢性疼痛和抑郁症潜在机制的相似性。
