The present study is the first examination of the relationships between SERT expression and kinetic parameters of 5-HT uptake. We have found statistically significant differences in Bmax
values between patients with FM and controls. Moreover, we found a negative correlation between symptom scores and the respective Bmax
versus tiredness, TPi and FIQ score). The platelet is considered to be a peripheral model of neuronal activity with respect to 5-HT function. In fact, previous studies have demonstrated that the same SERT is expressed in the central nervous system and platelets [14
]. Moreover, the identity between the two structures, as confirmed by sequence homologies through cloning studies [15
], has provoked a surge of different studies in neuropsychiatric disorders, given the possibility of exploring peripherally a mechanism of the central nervous system [26
]. Recently it has been proposed that altered serotonergic neuronal function might be related to the pathophysiology of FM [5
]. These findings prompted us to investigate the characteristics of SERT in the platelets of patients with FM. Bmax
values of [3
H]Paroxetine binding were assumed to represent SERT density and ligand binding affinity, respectively, whereas Vmax
values of [3
H]Serotonin uptake were taken as estimates of SERT rate and affinity, respectively. A very interesting observation was that both binding and uptake parameters differed significantly from those of healthy volunteers.
The patients with FM have fewer SERTs expressed on the cellular membrane than healthy subjects (a decreased Bmax, perhaps because the SERTs are less transcribed). Besides having fewer SERTs, patients with FM have a deficit in functionality (demonstrated by a decrease in transport rate).
Such combined changes in Bmax
values allow the inference that the efficiency of 5-HT uptake by platelet SERT is altered. Our previous studies demonstrated an alteration of SERT density and of the uptake rate of SERT in psychiatric patients [28
]. Consistent with this suggestion was the correlation analysis in the present study: the lower the density and rate of SERT on platelet membranes, the higher the severity of FM symptoms. Moreover, the Km
values were also positively correlated with tiredness, TPi and FIQ.
A reduced density and rate of SERT are consistent with previous observations indicating that levels of 5-HT are altered in patients with FM [30
]. The biophysiological mechanism of FM has been proposed to be similar to that in depression, and it has been suggested that this is likely to result from a neuroendocrine/neurotransmitter dysregulation [32
]. However, we suppose that the alterations in Bmax
values are not related to the pathophysiology of FM but are a consequence of FM. Our hypothesis is that a decrease in Bmax
of SERT is due to a pain stimulus [33
It has been shown that the decreased pain perception threshold during depression is likely to result from a dysfunction in several neurotransmitter systems, especially the serotoninergic one, which is also involved in the pathophysiology of depression [35
]. In addition, an excessive stimulation of peripheral 5-HT receptors would account for pain and might explain why the clinical use of 5-HT3
receptor antagonists such as tropisetron or granisetron can promote the relief of disturbance associated with FM [11
SERT has been investigated previously in patients with FM, with discordant results. Russell and colleagues [37
] found a higher Bmax
in patients with FM than in healthy controls, whereas other authors found normal Bmax
] using [3
H]Paroxetine or [3
]. In our experiments we used [3
H]Paroxetine, which binds with high affinity to a specific population of binding sites located on human platelets and neuronal membranes, associated with 5-HT uptake mechanisms [39
]. The present results indicate a decrease in the density and rate of platelet SERT in patients with FM, and allow us to propose a specific role for SERT in the pathogenesis of FM. In fact, we avoided the inclusion of patients with FM who had psychiatric components because it is known that in psychiatric disorders such as depression, the expression of SERT is altered [40
] and it is very difficult to identify the role of the two components in patients with FM who have comorbid psychiatric disorders. Thus, the changes in Bmax
demonstrated in our study may be due to FM only.
There is also a possible contribution from 5-HT to the aetiology of FM because of the efficacy of SSRIs in the management of chronic pain in idiopathic pain disorders [43
]. Thus, in view of the decreased Bmax
values found in our subset of mentally healthy patients, who were SSRI free, we propose that there is a compensatory mechanism in the central nervous system to relieve the pain. This may clarify the improvement in the therapeutic effectiveness of SSRI in the patients with FM.