Soluble Adenosine Deaminase Activity in Fibromyalgia Syndrome

Abstract

Fibromyalgia syndrome (FMS) is a widespread pain disorder of unknown etiology. It is characterized by tender points noted on physical examination and is often accompanied by a number of associated symptoms (1). Pain perception is altered in patients with FMS. For example, in genetically predisposed individuals, negative environmental influences may lead to central sensitization (CS) characterized by hyperalgesia, allodynia, an expansion of the receptive field and unpleasant poststimulus pain. CS implies that there is enhanced excitability of the dorsal horn neurons, with altered nociceptive information being provided to the brain. In the neuroanatomical circuits, the roles of a variety of substances, such as serotonin, dopamine, excitatory amino acids, cytokines, nitric oxide and purines, have been established (2). The antinociceptive effects of adenosine, which acts on A1 receptors, are well established (3). Recent studies have highlighted a reduction of circulating adenosine levels (4,5) in FMS. Moreover, a negative correlation was found between adenosine and the fibromyalgia impact questionnaire (FIQ), which was in agreement (5) with there being nociception alterations in FMS. Extracellular adenosine can pass through the cell membrane or can be deaminated to inosine by adenosine deaminase (ADA-EC 3.5.4.4.). ADA is a cytosolic enzyme, but it is also found on the surface of mononuclear cells (MCADA) in association with the CD26 glycoprotein, which exhibits dipeptidylpeptidase IV (DPPIV) activity. Moreover, a form of ADA that does not bind soluble CD26-DPPIV exists in the serum. Guieu (4) reported that there were low adenosine plasma concentrations in patients with FMS as a result of greater CD26–MCADA complex activities. In light of these findings, soluble ADA activity in patients with FMS and healthy subjects was assessed and compared in this study to evaluate the possible correlation between ADA activity and lower circulating adenosine levels that was previously reported in patients with FMS (5). The present study was approved by the ethical committee of the University Hospital of Cagliari and written informed consent was obtained from each woman for the use of her clinical information and blood samples. Twenty-two females affected by FMS (according to the 1990 and 2010 American College for Rheumatology Criteria (6,7)) and 22 controls were studied. The samples used were identical to those described in our previous study (5) and were stored at 80 C and never thawed. Total ADA activity (tADA) was estimated by the Giusti method (8). Statistical analysis was performed using the STAT VIEW5.0 software program developed by the SAS Institute Inc (Cary, NC). The tADA (mean ± SD) in patients with FMS (17.24 ± 5.95 U/l) was slightly increased compared with the controls (16.45 ± 4.58 U/l), but the difference was not statistically significant (Figure 1). The patients with FMS were divided in two groups (severe (n1⁄4 12) or mild (n1⁄4 10)) according to their FIQ scores (1); tADA activity was higher in the severe group (19.46 ± 7.13 /l) compared with the