Abstract
Abstract Nonsteroidal anti-inflammation drugs (NSAIDs) are developed as common analgesics for various clinical pain treatments. The mechanism of NSAIDs to suppress inflammation is to inhibit cyclooxygenase (COX) enzymes. The COX enzymes are required for conversion of arachidonic acid to prostagladins (PGs) and their metabolites play pivotal roles in inflammation processes. Despite the progress in medicine and pharmaceutics, drug administrations have less obvious variation and improvement. Limitation of the traditional administrations is that the applied drugs cannot be concentrated in a specific area within a specific organ. Therefore, high dosage is required for efficient curable concentration. In this thesis, IT (intrathecal) administration of NSAIDs in rats relieved thermal hyperalgesia through blockade of PGE2; however, it resulted in a significant short-term increase in spinal COX-2 expression. According to the WHO analgesic ladder, nonopioid drugs, including NSAIDs and acetaminophen, are recommended for patients with mild to moderate pain; whereas, opioids remain the most efficient pharmaceutical agents for patients with moderate to severe pain. However, drug tolerance and addiction deprive patients of the benefits of opioids and thus causing needless misery. Recently, based on the studies of molecular events in pain processing, engineering cell transplantation and gene therapy are exploited as new treatment strategies. In this study, we developed a model of cell transplantation using pituitary adenoma GH3 cells injected into rat spinal cord intrathecally. GH3 cells also possess similar antinociceptive properties to chromaffin cells. In the model, green fluorescernt protein was transfected into GH3 cells as a trace marker and the antinociceptive effects of GH3 cells in spinal cord were evaluated. However, tumor mass was developed near the IT administrated site and the histopathologic results demonstrated that the tumor was resulted from the injection of the GH3 cells. The present data implied that encapculation of the engineered tumor cells in a semi-permeable membrane is necessary to avoid tumor formation and then to exert therapeutic functions safely. Nevertheless, this novel subarachnoid tumor can be created consistently in rats and mimic pathological conditions of human spinal tumor, thereby may be useful for pathophysiological studies and development for pain control in spinal tumor.