The aim of this study, which completed the second year of a 5-year NIH funding cycle in July, 1996, is to better understand the central factors involved in the etiopathogenesis of altered pain perception in fibromyalgia (FM). We test 3 hypotheses drawn from a model which posits that neuroendocrine and immunologic abnormalities, characterized by decreases in cerebrospinal fluid (CSF) serotonin and increases in CSF substance P (SP), lead to sensitization of central nervous system structures involved in pain perception, i.e., thalamus and caudate nucleus. Decreases in regional cerebral blood flow (rCVF) to these structures serve as markers for this sensitization process and are associated with generalized low pain thresholds and other alterations in pain perception, independently of the effects of psychological status. The model also posits that elevated SCF SP may in part be due to SP messenger (m) RNA production by CSF leukocytes. We measure (1) rCBF to cortex, thalamus, and caudate nucleus, (2) CSF levels of serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), SP, CSF leukocyte number, and leukocyte SP mRNA level, (3) pain thresholds and (4) psychological status.