The American Pain Society estimates that 45% of the U.S. population seeks medical help for chronic pain at some point in their lives including 20 million arthritis sufferers, 40 million victims of chronic recurring headache, 8 million people with cancer, and the 15% of Americans with persistent back pain. One area of great interest is the identification of distinct biochemical profiles associated with specific pain conditions. Once identified, these biochemical profiles could be used to assist in the diagnosis of specific pain conditions and/or targeted for the development of new, more effective analgesic agents. This proposal outlines a pilot study using proteomic methods to identify proteins differentially regulated in cerebrospinal fluid (CSF) of one subset of chronic pain patients: patients scheduled for surgical treatment of chronic low back pain (LBP) due to degenerative disc disease (DDD). The DDD population was selected as a model for this pilot study because of the large patient base and the existence of objective criteria to measure the degree of disc degeneration by MRI. Interestingly, findings from imaging studies have frequently shown a low correlation between the extent of degenerative changes in this type of LBP and pain found upon physical evaluation. This may be because biochemical factors undetectable by imaging, rather than the degree of degeneration itself, play a more important role in development and perpetuation of the chronic pain state. Use of this LBP population will allow us to compare CSF biochemical profiles between DDD patients with and without pain. This design will allow us to distinguish CSF changes related to disc degeneration from those related to pain. We propose to utilize cutting edge proteomic methods to evaluate CSF changes in LBP (DDD) patients with severe pain compared to pain-free controls with and without lumbar ODD. Ultimately, our goal is to expand this study to a broader spectrum of chronic pain conditions in order to characterize biochemical changes in the central nervous system (CNS) of pain patients that are predictive of pain mechanism etiology and severity. Improved understanding of biochemical changes accompanying human chronic pain conditions could contribute to: a) more sensitive mechanism-based diagnostic criteria to distinguish different types of pain, b) validation of objective biomarkers to facilitate earlier diagnosis of developing pain states, c) objective endpoints of disease severity for use in clinical and research settings and d) the development of novel analgesic agents through the identification of novel disease-specific therapeutic targets. These advances would ultimately result in improved quality of life for millions of Americans living with chronic pain. [unreadable] [unreadable] [unreadable]