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Identification of therapeutic targets for the treatment of chronic pain is a major focus of the pharmaceutical industry. In particular efforts have focused on the discovery of novel agents for the treatment of neuropathic pain for which there is significant unmet medical need. Following nerve injury, as neuropathic pain develops many physiological changes occur in both the peripheral and central nervous system. To assess the changes, microarray gene chip technology has provided an excellent opportunity to examine RNA levels for multiple genes simultaneously. In the pain arena, most studies have focused on the evaluation of the expression profile of genes from entire tissues (dorsal root ganglion or spinal cord) that contain heterogeneous populations of neurons and glial cells, although a small number of studies have examined subpopulations of neurons that have been isolated by laser capture microdissection. While microarray is an excellent tool to identify changes in expression of thousands of transcripts simultaneously, additional detailed analysis of specific genes of interest is critical to the usefulness of this approach for new target identification. Confirmation of gene changes using quantitative reverse transcriptase polymerase chain reaction is a first step followed by when possible evaluation of protein levels using Western blot analysis and immunohistochemistry. Although this approach provides very useful information, it is not all encompassing as the function of a protein can change due to post-translational modifications with the overall level of the transcript being unaltered. However, microarray gene chip technology offers an excellent opportunity to visualize the many molecular transcripts that may play a role in the maintenance of neuropathic pain. Furthermore, recent trends are utilizing microarray gene chips to interrogate the genetic variability of patient populations that may lead to both the identification of new disease targets and tailoring of drug therapies to specific individuals. |
