Changes in the concentrations of amino acids in the cerebrospinal fluid that correlate with pain in patients with fibromyalgia: implications for nitric oxide pathways

Substance P (SP), a putative nociceptive transmitter, is increased in the C SF of patients with fibromyalgia syndrome (FMS). Because excitatory amino a cids (EAAs) also appear to transmit pain, we hypothesized that CSF EAAs may be similarly involved in this syndrome. We found that the mean concentrati ons of most amino acids in the CSF did not differ amongst groups of subject s with primary FMS (PFMS), fibromyalgia associated with other conditions (S FMS), other painful conditions not exhibiting fibromyalgia (OTHER) or age-m atched, healthy normal controls (HNC). However, in SFMS patients, individua l measures of pain intensity, determined using an examination-based measure of pain intensity, the tender point index (TPI), covaried with their respe ctive concentrations of glutamine and asparagine, metabolites of glutamate and aspartate, respectively. This suggests that re-uptake and biotransforma tion mask pain-related increases in EAAs. Individual concentrations of glyc ine and taurine also correlated with their respective TPI values in patient s with PFMS. While taurine is affected by a variety of excitatory manipulat ions, glycine is an inhibitory transmitter as well as a positive modulator of the N-methyl-D-asparate (NMDA) receptor. In both PFMS and SFMS patients, TPI covaried with arginine, the precursor to nitric oxide (NO), whose conc entrations, in turn, correlated with those of citrulline, a byproduct of NO synthesis. These events predict involvement of NO, a potent signaling mole cule thought to be involved in pain processing. Together these metabolic ch anges that covary with the intensity of pain in patients with FMS may refle ct increased EAA release and a positive modulation of NMDA receptors by gly cine, perhaps resulting in enhanced synthesis of NO. (C) 2000 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.