Conditioned pain modulation (CPM) is a promising psychophysical biomarker of central pain mechanisms because it significantly discriminates patients with chronic pain from healthy controls. Nevertheless, it is unclear in what extent CPM assessed experimentally is correlated with clinical manifestations of pain. To assess the concurrent validity of CPM, we performed a systematic review of the literature reporting correlations between CPM responses and pain intensity, disability, duration, and area in patients with different chronic pain conditions. We included 32 studies that altogether encompassed data from 1958 patients and provided 62 correlations. The majority of the results (69%) reported nonsignificant correlations between CPM efficiency and clinical manifestations of pain, whereas the remaining results showed a correlation between CPM reduction and worse clinical symptoms of pain. The modality of stimulation, the type of pain, and the stimulation site appear to be critical variables that influenced the pattern of results. Given that most of the studies were conducted with highly heterogeneous methodologies and unclear risk of bias, the findings highlight the need for future studies using standardized measures of clinical and experimental pain before considering CPM as a valid biomarker of pain. We discuss some guidelines to overcome the constraints in this promising line of research.

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.

Supplemental Digital Content is Available in the Text.In fibromyalgia, transcranial direct current stimulation over M1, CPFDL, or operculo-insular cortex relief affective symptoms more than sham; however, we do not recommend its use for the core symptoms.

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.

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.

Working memory (WM) is a critical process for cognitive functioning in which fibromyalgia (FM) patients could show cognitive disturbances. Dyscognition in FM has been explained by interference from pain processing, which shares the neural substrates involved in cognition and may capture neural resources required to perform cognitive tasks. However, there is not yet data about how pain is related to WM performance, neither the role that other clinical variables could have. The objectives of this study were (1) to clarify the WM status of patients with FM and its relationship with nociception, and (2) to determine the clinical variables associated to FM that best predict WM performance. To this end, 132 women with FM undertook a neuropsychological assessment of WM functioning (Digit span, Spatial span, ACT tests and a 2-Back task) and a complete clinical assessment (FSQ, FIQ-R, BDI-1A, HADS, PSQI, MFE-30 questionnaires), including determination of pain thresholds and tolerance by pressure algometry. Patients with FM seem to preserve their WM span and ability to maintain and manipulate information online for both visuospatial and verbal domains. However, up to one-third of patients showed impairment in tasks requiring more short-term memory load, divided attention, and information processing ability (measured by the ACT task). Cognitive performance was spuriously related to the level of pain experienced, finding only that pain measures are related to the ACT task. The results of the linear regression analyses suggest that sleep problems and fatigue were the variables that best predicted WM performance in FM patients. Future research should take these variables into account when evaluating dyscognition in FM and should include dynamic measures of pain modulation.

Fibromyalgia (FM) is a disease characterized by the presence of chronic and widespread musculoskeletal pain, which causes a high negative impact on the quality of life (QoL). Although there are many studies about the QoL of patients with FM, it is unknown which variables have a main influence on it. Therefore, in the present study, we aimed to determine which FM symptoms predict a worse QoL and also to establish whether lifestyle and multi-medication are associated to QoL. We assessed a sample of 134 women with FM using a semi-structured clinical interview to explore lifestyle (diet, exercise, smoking) and medication use, and questionnaires to cover the main symptoms of this disease and QoL (SF-36). We found that the patients with FM had a poor QoL, being “physical pain” and “vitality” the most affected domains. A linear regression analysis showed that depression and anxiety assessed by HADS were the FM symptoms which most significantly predicted QoL, explaining 49% of the variance. Concerning lifestyle/medication influences, we found that multiple drug treatment and smoking also predicted a worse QoL (14%). Moreover, patients who practiced exercise regularly showed better QoL than patients who did not (regardless of the severity of FM). Thus, our results suggest that treatment strategies to improve QoL in FM should be focused on improving psychological distress, promoting regular exercise and reducing smoking and multi-medication. The data highlights the role of positive self-management practices to improve QoL in FM.

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.