Leukemia inhibitory factor differentially regulates capsaicin and heat sensitivity in cultured rat dorsal root ganglion neurons
Leukemia inhibitory factor differentially regulates capsaicin and heat sensitivity in cultured rat dorsal root ganglion neurons
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DOI：
10.1016/j.npep.2007.12.005
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发表时间：
2008-04-01
期刊：
影响因子：
2.9
通讯作者：
Petersen, Marlen
中科院分区：
文献类型：
--
作者：
Engert, Sabine;Wendland, Jens R.;Petersen, Marlen
热痛觉过敏是神经性疼痛病症的一个标志。虽然确切的病理生理机制仍然难以捉摸，神经生长因子（NGF）和白血病抑制因子（LIF）被认为是关键的介质。它们的局部可用性或合成因神经损伤而改变，反过来，它们引起受影响神经元表型的变化。我们研究了LIF对辣椒素敏感性、热反应性和甘丙肽免疫反应性的影响，在没有补充NGF的情况下培养大鼠背根神经节神经元长达6天。使用双标记，热敏感/甘丙肽免疫反应（GAL-IR）和辣椒素敏感/GAL-IR神经元的比例进行了比较，随着时间的推移，在培养与甘丙肽免疫反应是伤害性神经元的标记。在没有LIF的情况下，在热敏神经元的群体内，在培养6小时和1天之间，GAL-IR神经元的比例也从17%增加到32%，以保持在这个水平。对于辣椒素敏感的神经元，神经元的比例也GAL-IR从6小时后的10%增加到18%，在第2天，然后下降到4%，在第4天。与此相反，LIF阻止热敏感/GAL-IR神经元比例的增加和辣椒素敏感/GAL-IR神经元的减少。此外，有证据表明LIF调节不同于TRPV-1的热受体的表达。(c)2008爱思唯尔有限公司保留所有权利。
Thermal hyperalgesia is one hallmark of neuropathic pain conditions. Although the exact pathophysiological mechanisms remain elusive, nerve growth factor (NGF) and leukemia inhibitory factor (LIF) are considered key mediators. Their local availability or synthesis are altered by nerve damage and, in turn, they entail changes in phenotype of affected neurons. We examined the effects of LIF on capsaicin sensitivity, heat responsiveness, and galanin immuno reactivity in rat dorsal root ganglion neurons cultured for up to 6 days without supplemented NGF. Using double labeling, the proportions of heat-sensitive/galanin-immunoreactive (GAL-IR) and capsaicin-sensitive/GAL-IR neurons were compared over time in culture with galanin immunoreactivity being a marker for nociceptive neurons.The time course of the proportions of neurons responding to heat (44 degrees C) or capsaicin (1 mu M) which also were GAL-IR was differently affected by LIF. In the absence of LIF, within the population of heat-sensitive neurons, the proportion of neurons also GAL-IR increased from 17% to 32% between 6 h and 1 day in culture to stay at this level. For the capsaicin-sensitive neurons, the proportion of neurons also GAL-IR increased from 10% after 6 h to 18% at day 2 and then decreased to 4% at day 4. In contrast, LIF prevented the increase in the proportion of heat-sensitive/GAL-IR neurons and the decrease of capsaicin-sensitive/GAL-IR neurons.The results suggest that LIF partially prevents TRPV-1 downregulation in NGF-deprived nociceptive galaninergic DRG neurons. Furthermore, there is evidence that LIF regulates the expression of a heat receptor distinct from TRPV-1. (c) 2008 Elsevier Ltd. All rights reserved.