Nicotine stimulates expression of proteins implicated in peripheral and central sensitization.
Nicotine stimulates expression of proteins implicated in peripheral and central sensitization.
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DOI：
10.1016/j.neuroscience.2015.01.034
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发表时间：
2015-04-02
期刊：
影响因子：
3.3
通讯作者：
Durham PL
中科院分区：
文献类型：
--
作者：
Hawkins JL;Denson JE;Miley DR;Durham PL
尼古丁依赖的疼痛患者报告疼痛强度的发生率和严重程度显著增加。本研究的目的是确定长期尼古丁给药对三叉神经系统外周和中枢致敏性发展中涉及的炎症蛋白的影响。采用行为学、免疫组织化学和微阵列研究来研究Sprague道利大鼠中通过Alzet®渗透泵每日给予尼古丁持续14天的影响。全身尼古丁给药引起三叉神经元机械刺激的伤害性退缩显著增加。尼古丁刺激三叉神经脊束核中促炎信号转导蛋白磷酸化细胞外信号调节激酶（p-ERK）、磷酸化c-Jun N-末端激酶（p-JNK）和蛋白激酶A（PKA）的表达。尼古丁还促进了胶质细胞酸性蛋白（GFAP）（活化星形胶质细胞的生物标志物）和小胶质细胞生物标志物离子化钙结合衔接分子1（Iba 1）表达的升高。类似地，11种细胞因子的水平显著升高，其中TNF-α的表达增加最多。PKA、p-ERK和p-JNK在三叉神经节神经元中的水平被尼古丁增加。我们的研究结果表明，长期全身给予尼古丁可促进三叉神经脊束核和三叉神经节中关键蛋白表达的持续行为和细胞变化，这些蛋白与外周和中枢致敏的发展和维持有关。
Pain patients who are nicotine dependent report a significantly increased incidence and severity of pain intensity. The goal of this study was to determine the effects of prolonged nicotine administration on inflammatory proteins implicated in the development of peripheral and central sensitization of the trigeminal system. Behavioral, immunohistochemical, and microarray studies were utilized to investigate the effects of nicotine administered daily for 14 days via an Alzet®osmotic pump in Sprague Dawley rats. Systemic nicotine administration caused a significant increase in nocifensive withdrawals to mechanical stimulation of trigeminal neurons. Nicotine stimulated expression of the pro-inflammatory signal transduction proteins phosphorylated-extracellular signal-regulated kinase (p-ERK), phosphorylated-c-Jun N-terminal kinase (p-JNK), and protein kinase A (PKA) in the spinal trigeminal nucleus. Nicotine also promoted elevations in the expression of glial fibrillary acidic protein (GFAP), a biomarker of activated astrocytes, and the microglia biomarker ionized calcium-binding adapter molecule 1 (Iba1). Similarly, levels of eleven cytokines were significantly elevated with the largest increase in expression of TNF-α. Levels of PKA, p-ERK, and p-JNK in trigeminal ganglion neurons were increased by nicotine. Our findings demonstrate that prolonged systemic administration of nicotine promotes sustained behavioral and cellular changes in the expression of key proteins in the spinal trigeminal nucleus and trigeminal ganglion implicated in the development and maintenance of peripheral and central sensitization.
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影响因子：
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