DNA MICROARRAY ANALYSIS OF GENE EXPRESSION IN THE HYPOTHALAMUS OF SOCIAL-DEFEAT STRESS-INDUCED CHRONIC PAIN MODEL MICE

Abstract Background Exposure to chronic stresses affects the sensitivity to pain stimuli and is associated with the development of chronic pain. However, the molecular mechanisms underlying the pathogenesis of stress-induced chronic pain remain unclear. Our previous study demonstrated that mice subjected to repeated social defeat stress showed a dramatically longer prolongation of postsurgical pain than non- stressed mice. Aims & Objectives In this study, we performed DNA microarray analysis within the hypothalamus of these stressed mice to investigate gene expression changes when pain becomes chronic due to stress. Methods Male C57BL/6J mice were subjected to social defeat stress for 10 days. The 5 mm incisions were made in the right paw plantar region of the mice as a postoperative pain model. The von Frey test was used to evaluate pain in response to mechanical stimuli. On day 7 of postoperative pain, the changes of gene expression in the hypothalamus tissues were evaluated by DNA microarray analysis. Only genes with expression variation were extracted based on mice subjected to postoperative pain under non-stressed conditions. Genes with a gene expression ratio>2.0 or ratio<0.5 were defined as genes with altered expression. Results Nonstress-operation mice showed an increase mechanical allodynia to the 0.16g firmament, which occurred at day 1 post-paw incision and continued for 4 days in comparison with non-stress-sham mice. On the other hand, the mechanical allodynia in stress-operation mice continued for 7 days. At postoperative day 7, DNA microarray analysis revealed that 278 genes were more than doubled in stressed mice with pain, whereas 137 genes were reduced by less than half compared to non-stressed mice. Discussion & Discussion These results demonstrated that the main changes included several genes involved in the lipid metabolism, arachidonic acid cascade, inflammatory and immune responses, and hormone. Detailed analysis of the fluctuating genes is currently underway.