Approaches to Cloning of Pain-Related Ion Channel Genes
Molecular pain research is a relatively new and rapidly expanding field that represents advancement in conventional pain research. One of the fundamentals of molecular pain involves the cloning of genes and especially the ion channels specifically involve
- PDF / 506,375 Bytes
- 17 Pages / 504.57 x 720 pts Page_size
- 105 Downloads / 198 Views
1
Introduction Substantial advances in our understanding of pain mechanisms during the past two decades can be traced to the application of molecular biology in pain research (1, 2). This new period, which can be labeled as molecular pain research, gave rise to a fully recognized category in the pain field, leading to the creation of dedicated and specialized journals including Molecular Pain. In regard to the field of pain, molecular biology can offer several powerful approaches, including methods and tools to identify genes and the underlying molecular mechanisms specifically involved in variety of physiological and pathophysiological acute and chronic pain conditions. Thus, modern molecular biology has following main approaches: 1. Cloning: Cloning methods were developed through a string of seminal discoveries in the 1970s and early 1980s (3, 4). The application of modern cloning approaches and methods to pain research led to the identification of new transcription factors, cytoplasm proteins, adapter proteins, receptors, and ion channels involved in generating, modulating, and propagating
Nikita Gamper (ed.), Ion Channels: Methods and Protocols, Methods in Molecular Biology, vol. 998, DOI 10.1007/978-1-62703-351-0_1, © Springer Science+Business Media, LLC 2013
3
4
Armen N. Akopian
action potentials along the nociceptive pathways (5–13). Cloning of the genes involved in certain physiological conditions is considered a primer and ultimately a starting point for all further functional studies on the underlying molecular mechanisms. Eventually these functional studies, which also utilize molecular biology approaches, result in a true appreciation of the importance of cloned genes (1). 2. Identification of regulatory pathways: Molecular biology approaches are utilized to identify transcriptional, posttranscriptional (i.e., splice variants), translational, and posttranslational changes in gene expressions after pathological painful conditions such as tissue damage, inflammation, and nerve damage (14, 15). These alterations underlie neural reorganization (i.e., “plasticity”) in the nociceptive signal transduction pathways, which include sensory neurons, spinal cord and brain stem neurons, and certain brain regions including the hypothalamus. It is presumed that chronic pain conditions are manifestations of neuronal plasticity and therefore, uncovering the genes and molecular mechanisms contributing to the generation of this plasticity could support discoveries of novel analgesic targets and promote designs of novel anti-pain therapeutic strategies (16). 3. Identification of mutated genes using genetics: Molecular genetics tools are widely used to identify genes responsible for particular phenotypes in defined animal lines or genetic mutations in humans leading to diseases, such as congenital insensitivities to pain (17, 18). As the human genome project approaches completion, “new” genes involved in specific pain conditions or chronic pain diseases may be uncovered (19, 20). Moreover, molecular genetics approach
Data Loading...
