Levels of 5-hydroxyindoleacetic Acid, Gamma-aminobutyric Acid and Nitric Oxide Metabolites in Cerebrospinal Fluid of Egyptian Women Suffering of Fibromyalgia

Hypothesis: Fibromyalgia (FM) is a complex chronic disorder predominately affects women. The lack of objective analytical image for diagnosis and prognosis of FM attract many investigators to evaluate the neuroendocrine changes in body fluids that may be related to the pathophysiology of FM. Objectives & Methodology: To compare the levels of 5hydroxyindoleacetic acid (5-HIAA, serotonin metabolite), gamma-aminobutyric acid (GABA) and nitric oxide (NO) metabolites in cerebrospinal fluid (CSF) of normoglycemic women suffering of FM with those of control group. In addition, levels of insulin, insulin like growth factor-1 (IGF-1), cortisol, 5-hydroxytryptamine (5-HT, serotonin), GABA, and NO metabolites were determined in serum of FM patients compared to control group. Moreover, the correlations between all the studied parameters were performed. Results: The present study showed altered serum levels of insulin and cortisol in normoglycemic women suffering of FM (n=15) compared to those of control group (n=15). However, the data did not find significant differences between serum levels of IGF-1 in women suffering of FM and those in healthy women. Cortisol levels in FM sera were inversely correlated with the number of tender points (r=-0.76, p<0.001). Also, negative CSF in Egyptian Women Suffering of Fibromyalgia Saad, Mandour & Kotb 696 correlation was observed between serum IGF-1 levels and age of FM patients (r=-0.63, p< 0.05). Low levels of serum 5-HT and CSF 5-HIAA were also noticed among women suffering of FM. A decrement of both serum and CSF levels of GABA in those patients compared to controls was detected. Furthermore, there was a positive correlation between serum GABA levels and serum cortisol levels (r=0.61, p< 0.05), and between CSF GABA and 5-HT (r=0.56, p< 0.05). However, CSF GABA levels were negatively correlated with age of women suffering of FM. These findings may clarify the significant role of GABA in the pathogenesis of FM. A higher serum and CSF levels of NO metabolites were detected in FM patients than in control group. In addition, serum levels of NO metabolites were correlated with those levels in CSF (r=0.63, p< 0.05). The involvement of NO in pain process was revealed by a strong correlation between serum and CSF levels of NO metabolites with the number of tender points (r=0.91, p< 0.001; r=0.73, p< 0.01 respectively). Also, by a negative correlation between serum levels of NO metabolites and serum cortisol levels (r=0.70, p< 0.01) in FM patients. Conclusions: The changes in the levels of studied hormones and neurotransmitters in women suffering of FM support the hypothesis of neuroendocrine involvement in FM pathogenesis. The current study suggested that GABA and NO may play a role in modulating FM. Alterations of their levels in serum and CSF of women suffering of FM and their correlations with age, number of tender points and/ or cortisol may confirm this suggestion. Accordingly, this investigation recommended the examination of GABAergic agents, NO synthase (NOS) inhibitors, or antioxidants for therapy of various symptoms in women suffering of FM. Furthermore, our study may find utility of these neurotransmitters as possible markers of FM, but this study warrant more investigations to confirm these findings.