PAIN, SUPRASPINAL SEROTONIN AND NEUROTROPHIC FACTORS

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Fibromyalgia comprises a subset of hyperalgesic or allodynic syndromes characterized by a dysregulation of nociceptive processing and neuroendocrine function. Chronic generalized pain together with decreased endocrine and autonomic responsiveness to stress has been observed. Clearly, supraspinal systems regulate nociceptive pathways, but our understanding of the neuromodulators participating in chronic pain pathways is quit incomplete. Therapeutically, drugs that alter serotonergic neurotransmission show modest effectiveness in these disorders. This study will utilize in vivo microdialysis to investigate monoamine release in supraspinal sites important in endocrine (paraventricular nucleus of the hypothalamus) and pain regulating (ventral lateral thalamus) systems in an animal model of chronic pain. In addition, the effects of chronic pain on responsiveness of the autonomic nervous system will also be assessed. Neurotrophic factors NGF, FGF-1 and FGF-2 are prominently expressed in the central nervous system however, there is a paucity of information on how their expression changes in the setting of chronic pain. In situ hybridization and immunohistochemical localization of these growth factors will be conducted on brain from Sprague-Dawley rats with adjuvant induced arthritis (a model of chronic pain), rats having undergone partial sciatic nerve ligation (a model of acute pain) and sham treated control rats. In vivo experiments will utilize antigens oligonucleotide technology to modulate c-fos, NGF, FGF-1 and FGF-2 expression. Microdialysis will allow us to dynamically assess Serotonin, Substance P and NGF levels in selected regions of rat brain following antigens oligonucleotide delivery. This proposal will provide a novel approach to dynamically measure critical compounds involved in nociceptive transmission.