A deficit in peripheral serotonin levels in major depressive disorder but not in chronic widespread pain.

OBJECTIVES: It has been proposed that serotonin dysfunctions underlie the pathophysiology of various mood disorders (including major depressive disorder, MDD) and chronic pain conditions characterized by deficient pain inhibition, such as fibromyalgia (FM). There is reliable data showing that serotonin disturbances are involved in the pathophysiology of MDD. However, in the case of FM, results published so far are less consistent. Therefore, the current cross-sectional study sought to measure plasma serotonin levels in FM patients, MDD patients, and healthy controls (HC). METHODS: Twenty-nine FM patients, 17 MDD patients, and 57 HC were recruited who did not differ in terms of age, sex, and the presence or absence of a regular menstrual cycle. Plasma samples were analysed with mass spectrometry. RESULTS: Serotonin levels were decreased in MDD patients, relative to FM patients and HC. Post hoc analyses showed that serotonin levels were decreased in FM patients taking antidepressants, relative to HC, but not in drug-free FM patients. Moreover, serotonin levels were negatively correlated with mood symptoms across groups. DISCUSSION: Our results further confirm that MDD is associated with decreased serotonin levels, but that serotonin levels are not altered in FM per se, and suggest that 5-Hydroxytryptamine is related to mood symptoms in these patient groups. Our results also suggest that the taking of antidepressant is a major confound to consider when studying serotonin functioning in FM. The long-term use of antidepressants in FM may lead to serotonin depletion. Conversely, serotonin depletion may be before the taking of antidepressants in FM.

Pain inhibition is deficient in chronic widespread pain but normal in major depressive disorder.

BACKGROUND: Given the complex relationships between fibromyalgia and major depressive disorder (MDD), it has been suggested that fibromyalgia is a "masked" MDD. In experimental settings, fibromyalgia is associated with lowered pain thresholds (hyperalgesia) and deficient pain inhibition. Similarly, it has been recently proposed that the proneness of patients with MDD to develop chronic pain results from a deficit in pain inhibition. This cross-sectional study measured experimentally induced pain perception and inhibition in patients with MDD and patients with fibromyalgia. METHOD: Participants were 29 patients with fibromyalgia (American College of Rheumatology criteria), 26 patients with MDD (DSM-IV criteria), and 40 healthy controls who did not differ in age, sex, or the presence or absence of a menstrual cycle. Data were collected between June 2007 and May 2008. Thermal stimuli were used to measure pain thresholds. Pain inhibition was elicited using a tonic thermal test (Peltier thermode) administered before and after activation of the diffuse noxious inhibitory controls (DNIC) by means of a cold pressor test. RESULTS: Thermal pain thresholds were higher in healthy controls compared to patients with MDD and patients with fibromyalgia. Pain ratings during the cold pressor test were lower in healthy controls and patients with MDD relative to patients with fibromyalgia. Finally, DNIC efficacy was stronger in healthy controls compared to patients with fibromyalgia, while no significant differences were found between healthy controls and patients with MDD. CONCLUSIONS: Our results suggest that (1) fibromyalgia and MDD are both associated with signs of hyperalgesia, (2) hyperalgesia is more pronounced in fibromyalgia, and (3) the deficit of pain inhibition is specific to fibromyalgia. As such, these results suggest that there is an overlap between fibromyalgia and MDD, but that fibromyalgia can be distinguished from MDD in terms of DNIC efficacy.

No relationship between the ins del polymorphism of the serotonin transporter promoter and pain perception in fibromyalgia patients and healthy controls.

BACKGROUND: In animals, decades of research have shown that serotonin (5-HT) is involved in endogenous pain inhibition systems, which are deficient in chronic pain disorders such as fibromyalgia (FM). In humans, there is preliminary evidence showing that 5-HT is involved in the FM pathophysiology. In the current endophenotyping study, we sought to investigate, for the first time in humans, the relationships between the serotonin transporter promoter region (5-HTTLPR) polymorphism and experimentally-induced pain perception/inhibition in healthy controls (HC) and FM patients. METHODS: Participants were 58 FM patients and 60 HC, who did not differ in age, sex or menstrual cycle. Thermal stimuli were used to measure pain thresholds. Pain inhibition was elicited using a tonic thermal test (Peltier thermode) administered before and after activation of the diffuse noxious inhibitory controls (DNIC) by means of a cold-pressor test (CPT). RESULTS: Thermal pain thresholds were higher in HC compared to FM patients. Pain ratings during the CPT were lower in HC, relative to FM patients. Also, DNIC efficacy was stronger in HC compared to FM patients. However, there was no relationship between 5-HTTLPR and experimentally-induced pain perception/inhibition. DISCUSSION: Our results further confirm that FM is associated with thermal hyperalgesia and deficient DNIC. However, we found no evidence showing that the 5-HTTLPR polymorphism influences pain perception and DNIC. Potential reasons for this negative result will be discussed. Further endophenotyping studies of 5-HT-related gene polymorphisms are required to ascertain the potential relationships between 5-HT and human pain perception/inhibition.

DRD3 Ser9Gly polymorphism is related to thermal pain perception and modulation in chronic widespread pain patients and healthy controls.

UNLABELLED: Experimental studies showed that dopamine influences pain perception in healthy volunteers. Dopamine dysfunctions have been linked to the physiopathology of fibromyalgia (FM), which is associated with hyperalgesia and deficient pain inhibition. We sought to investigate the relationships between catecholamine-related polymorphisms [dopamine-D(3) receptor (DRD3) Ser9Gly and catechol-O-methyltransferase (COMT) Val158Met] and thermal pain measures in healthy subjects and FM patients. Seventy-three subjects (37 FM patients and 36 controls) participated in this study. Thermal pain thresholds (TPTs) were measured using a Peltier thermode. Inhibitory systems were elicited using a thermal tonic pain stimulation administered before and after activation of the diffuse noxious inhibitory controls (DNIC) by means of a cold-pressor test. Genetic analyses were performed using polymerase chain reaction. Regression analyses were performed across and within groups. FM was associated with lower TPTs and deficient pain inhibition. DRD3 Ser9Gly polymorphism predicted (1) DNIC efficacy across groups and (2) thermal TPTs in FM patients. COMT Val158Met and thermal pain measures were not related. These preliminary results suggest that the DRD3 Ser9Gly polymorphism influences DNIC efficacy and TPTs and that this latter relationship is present only in FM patients. Two core psychophysical features of FM appear to be significantly influenced by limbic dopamine functioning. PERSPECTIVE: This experimental study is the first to relate DNIC and TPTs to a functional polymorphism of limbic dopamine-D3 receptors. As lowered pain thresholds and deficient pain inhibition are 2 core features of fibromyalgia, these preliminary results may help identify a subgroup of FM patients who require closer medical attention.