Conditioned pain modulation (CPM) paradigm type affects its sensitivity as a biomarker of fibromyalgia.

Fibromyalgia (FM) is a widespread chronic pain syndrome, possibly associated with the presence of central dysfunction in descending pain inhibition pathways. Conditioned Pain Modulation (CPM) has been proposed as a biomarker of FM. Nonetheless, the wide variety of methods used to measure CPM has hampered robust conclusions being reached. To clarify the validity of CPM as a biomarker of FM, we tested two CPM paradigms (parallel and sequential) in a sample of 23 female patients and 23 healthy women by applying test (mechanical) stimuli and conditioning (pressure cuff) stimuli. We evaluated whether CPM indices could correctly classify patients and controls, and we also determined the correlations between the indices and clinical variables such as symptomatology, disease impact, depression, quality of life, pain intensity, pain interference, fatigue and numbness. In addition, we compared the clinical status of CPM responders (efficient pain inhibitory mechanism) and non-responders. We observed that only parallel CPM testing correctly classified about 70% of patients with FM. In addition, more than 80% of healthy participants were found to be responders, while the rate was about 50% in the FM patients. The sequential CPM test was not as sensitive, with a decrease of up to 40% in the response rate for both groups. On the other hand, we did not observe any correlation between CPM measures and clinical symptoms. In summary, our findings demonstrate the influence of the CPM paradigm used and confirm that CPM may be a useful marker to complement FM diagnosis. However, the findings also cast doubts on the sensitivity of CPM as a marker of pain severity in FM.

Active and sham transcranial direct current stimulation (tDCS) improved quality of life in female patients with fibromyalgia.

PURPOSE: Fibromyalgia (FM) is a chronic pain syndrome with a strong impact on quality of life (QoL). Treatment of this condition remains a challenge, due to the scarce evidence for the effectiveness of the therapeutic approaches available. Current attention is focused on transcranial direct current stimulation (tDCS), which has yielded promising results for pain treatment. Rather than focusing only on pain relief, in this study, we aimed to determine how active or sham tDCS (over three cortical targets -the primary motor cortex, the dorsolateral prefrontal cortex and the operculo-insular cortex-) affect QoL in patients with FM. METHODS: Using a double-blind, placebo-controlled design, we applied fifteen tDCS sessions of 20' to initial 130 participants (randomized to any of the four treatment groups). We evaluated the QoL (assessed by SF-36) and the symptoms' impact (assessed by FIQ-R) in baseline, after treatment and at 6 months follow-up. RESULTS: All groups were comparable as regards age, medication pattern and severity of symptoms before the treatment. We found that QoL and symptoms' impact improved in all treatment groups (including the sham) and this improvement lasted for up to 6 months. However, we did not observe any group effect nor group*treatment interaction. CONCLUSIONS: After the intervention, we observed a non-specific effect that may be due to placebo, favoured by the expectations of tDCS efficacy and psychosocial variables inherent to the intervention (daily relationship with therapists and other patients in the clinic). Therefore, active tDCS is not superior to sham stimulation in improving QoL in FM.

Effects of intensity, attention and medication on auditory-evoked potentials in patients with fibromyalgia.

Fibromyalgia (FM) has been associated to an increased processing of somatosensory stimuli, but its generalization to other sensory modalities is under discussion. To clarify this, we studied auditory event-related potentials (AEPs) to stimuli of different intensity in patients with FM and healthy controls (HCs), considering the effects of attention mechanisms and medication. We performed two experiments: In study 1 (n = 50 FM, 60 HCs), the stimuli were presented randomly within the sequence; in study 2 (n = 28 FM, 30 HCs), they were presented in blocks of the same intensity. We analyzed intensity and group effects on N1-P2 amplitude and, only for the FM group, the effect of medication and the correlation between AEPs and clinical variables. Contrary to the expectation, the patients showed a trend of reduced AEPs to the loudest tones (study 1) or no significant differences with the HCs (study 2). Medication with central effects significantly reduced AEPs, while no significant relationships between the N1-P2 amplitude/intensity function and patients' symptoms were observed. The findings do not provide evidence of augmented auditory processing in FM. Nevertheless, given the observed effect of medication, the role of sensory amplification as an underlying pathophysiological mechanism in fibromyalgia cannot be discarded.

Neural correlates of cognitive dysfunction in fibromyalgia patients: Reduced brain electrical activity during the execution of a cognitive control task.

OBJECTIVES: Fibromyalgia (FM) is a generalized chronic pain syndrome of unknown aetiology. Although FM patients frequently complain of cognitive dysfunction, this is one of the least studied symptoms. Research on brain activity associated with the perceived cognitive impairment is particularly scarce. To address this gap, we recorded the brain electrical activity in participants during a cognitive control task. METHODS: Electroencephalograms (EEGs) were recorded in 19 FM patients and 22 healthy controls (all women) while they performed the Multi-Source Interference Task (MSIT). We analyzed the amplitude of the frontal N2 and parietal P3 components elicited in control and interference trials and their relation with reaction times. We also explored the relationship of perceived cognitive dysfunction, assessed using visual analogue scales (VAS) and the Memory Failures of Everyday (MFE-30) test, with N2 and P3 amplitudes. RESULTS: The N2 amplitudes were smaller in FM patients than in controls and were negatively associated with cognitive complaints. Unlike patients, healthy controls showed significant differences in the amplitude of P3 obtained from control vs. interference trials of the MSIT. Smaller N2 and P3 amplitudes were associated to longer reaction times. CONCLUSIONS: The findings suggest a reduction in frontal brain activity during performance of an interference task, which was associated with the patients' cognitive complaints. Findings on P3 suggest altered modulation of attention according to the task demands in FM patients. Deficits in flexibility in the allocation of attentional resources and cognitive control during complex tasks may explain the dyscognition reported by chronic pain patients.

Increased neural noise and impaired brain synchronization in fibromyalgia patients during cognitive interference.

Fibromyalgia (FM) and other chronic pain syndromes are associated with cognitive dysfunction and attentional deficits, but the neural basis of such alterations is poorly understood. Dyscognition may be related to high levels of neural noise, understood as increased random electrical fluctuations that impair neural communication; however, this hypothesis has not yet been tested in any chronic pain condition. Here we compared electroencephalographic activity (EEG) in 18 FM patients -with high self-reported levels of cognitive dysfunction- and 22 controls during a cognitive control task. We considered the slope of the Power Spectrum Density (PSD) as an indicator of neural noise. As the PSD slope is flatter in noisier systems, we expected to see shallower slopes in the EEG of FM patients. Higher levels of neural noise should be accompanied by reduced power modulation and reduced synchronization between distant brain locations after stimulus presentation. As expected, FM patients showed flatter PSD slopes. After applying a Laplacian spatial filter, we found reduced theta and alpha power modulation and reduced midfrontal-posterior theta phase synchronization. Results suggest higher neural noise and impaired local and distant neural coordination in the patients and support the neural noise hypothesis to explain dyscognition in FM.