We hypothesize that the proteome obtained from human cerebrospinal fluid (CSF) differs between controls and those patients who are diagnosed with idiopathic low back pain because our preliminary data clearly demonstrate significant differences in those two groups in the amount of a specific opioid and a specific tachykinin neuropeptide. We will expand our study to include proteins and enzymes. We will experimentally test our hypothesis by first qualitatively and quantitatively analyzing the opioid and tachykinin neuropeptidergic systems in the CSF proteome, including each neuropeptide precursor and associated enzymes. Endomorphins and other pertinent neuropeptide systems will also be studied. The proteome will be analyzed with electrophoresis and mass spectrometry. We will analyze the neuropeptide-containing proteins in the metabolic cascade that synthesizes each neuropeptide in the neuron: DNA -> RNA -> intermediate-sized proteins-> neuropeptide ->metabolites. That cascade involves several different enzymes (prohormone convertases, aminopeptidases, peptidyl glycine-amidating monooxygenase, enkephalinase, and others). A differential spinal diagnosis with lidocaine readily differentiates among the three different low back pain patient populations-controls (pain; non-pain patients), physiologic responders (require surgery), and nonphysiologic responders. The non-physiologic responders contain two subgroups: malingerers and idiopathic low back patients. Malingerers are readily identified (> ca. 95% accuracy) by a psychological test (MMPI), and are readily excluded from this study. Our hypothesis focuses only on the idiopathic low back pain group, which has no known reason for their pain.
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| Terry, Doris E; Umstot, Edward; Desiderio, Dominic M (2004) Optimized sample-processing time and peptide recovery for the mass spectrometric analysis of protein digests. J Am Soc Mass Spectrom 15:784-94 |
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| Yuan, Xianglin; Desiderio, Dominic M (2002) Protein identification with Teflon as matrix-assisted laser desorption/ionization sample support. J Mass Spectrom 37:512-24 |
| Yuan, Xianglin; Russell, Tara; Wood, George et al. (2002) Analysis of the human lumbar cerebrospinal fluid proteome. Electrophoresis 23:1185-96 |
