LaCroix-Fralish Michael L, Tawfik Vivianne L, Spratt Kevin F, DeLeo Joyce A
Department of Pharmacology and Toxicology, Dartmouth College, Hanover.
J Mol Neurosci. 2006;30(3):283-95. doi: 10.1385/JMN:30:3:283.
Considerable evidence indicates that there are sex-related differences in clinical and experimental pain sensitivity. In the present study, we sought to determine what genes were expressed in the spinal cord in a sexually dimorphic manner. We first analyzed global gene expression in the lumbar spinal cord of uninjured male and female rats using the Affymetrix RAE230A GeneChip platform in order to identify genes that are selectively expressed in male and female rats at a basal level. We subsequently analyzed global gene expression in the lumbar spinal cord of male and female rats at two time points (7 days and 14 d) following a rodent model of lumbar radiculopathy (L5 nerve root ligation) in order to determine what genes were regulated in a sexually dimorphic manner following nerve root injury. We utilized a linear regression analysis method to identify genes that were significantly different from the corresponding sham surgical controls. The expression patterns of several genes of interest were subsequently confirmed using RT-PCR. Our findings demonstrate significant differences in lumbar spinal cord gene expression in both uninjured and injured (L5 nerve root ligation) male and female rats. Further confirmation of a subset of the genes identified Neuregulin 1 and its high affinity receptor, ErbB4, Tachykinin 1, and Metabotropic glutamate receptor 6 as female specific genes upregulated following L5 nerve root injury. These findings provide several target genes for further study that may elucidate the neurochemical mechanisms underlying sex differences in pain sensitivity and lead to improved treatments for chronic pain syndromes.
大量证据表明，临床和实验性疼痛敏感性存在性别相关差异。在本研究中，我们试图确定哪些基因在脊髓中以性别二态性方式表达。我们首先使用Affymetrix RAE230A基因芯片平台分析未受伤雄性和雌性大鼠腰段脊髓的整体基因表达，以识别在基础水平上在雄性和雌性大鼠中选择性表达的基因。随后，我们在腰椎神经根病（L5神经根结扎）啮齿动物模型后的两个时间点（7天和14天）分析雄性和雌性大鼠腰段脊髓的整体基因表达，以确定神经根损伤后哪些基因以性别二态性方式受到调节。我们采用线性回归分析方法来识别与相应假手术对照组有显著差异的基因。随后使用RT-PCR证实了几个感兴趣基因的表达模式。我们的研究结果表明，在未受伤和受伤（L5神经根结扎）的雄性和雌性大鼠中，腰段脊髓基因表达存在显著差异。对一部分基因的进一步证实确定了神经调节蛋白1及其高亲和力受体ErbB4、速激肽1和代谢型谷氨酸受体6为L5神经根损伤后上调的雌性特异性基因。这些发现为进一步研究提供了几个靶基因，可能阐明疼痛敏感性性别差异背后的神经化学机制，并导致慢性疼痛综合征治疗方法的改进。
