Effect of Operational Variables on Supercritical Foaming of Caffeic Acid-Loaded Poly(lactic acid)/Poly(butylene adipate-co-terephthalate) Blends for the Development of Sustainable Materials.

Expanded polystyrene will account for 5.3% of total global plastic production in 2021 and is widely used for food packaging due to its excellent moisture resistance and thermal insulation. However, some of these packages are often used only once before being discarded, generating large amounts of environmentally harmful plastic waste. A very attractive alternative to the conventional methods used for polymer processing is the use of supercritical carbon dioxide (scCO2) since it has mass-transfer properties adapted to the foam morphology, generating different path lengths for the diffusion of active compounds within its structure and can dissolve a wide range of organic molecules under supercritical conditions. The objective of this research was to evaluate the effect of operational variables on the process of caffeic acid (CA) impregnation and subsequent foaming of polylactic acid (PLA) as well as two PLA/poly(butylene-co-terephthalate-adipate) (PBAT) blends using scCO2. The results showed an increase in the degree of crystallinity of the CA-impregnated samples due to the nucleation effect of the active compound. On the other hand, SEM micrographs of both films and foams showed significant differences due to the presence of PBAT and its low miscibility with PLA. Finally, the results obtained in this work contribute to the knowledge of the important parameters to consider for the implementation of the impregnation and foaming process of PLA and PLA/PBAT blends with potential use in food packaging.

Colorimetric Indicator Based on Gold Nanoparticles and Sodium Alginate for Monitoring Fish Spoilage.

In this work, a colorimetric indicator based on gold nanoparticles (AuNP) and a biodegradable and eco-friendly polymer (sodium alginate, Alg.), was developed for the real-time detection of fish spoilage products. The AuNPs and the colorimetric indicator were characterized using UV-VIS, FTIR spectroscopies, TGA, DSC, XRD, TEM, and colorimetry. The UV-VIS spectrum and TEM showed the successful synthesis, the spherical shape, and the size of AuNPs. The results indicated color changes of the indicator in packaged fish on day 9 of storage at a refrigerated temperature (5 °C. These results showed the successful application of the colorimetric indicator in the detection of TVB-N in packaged fish.

Ethylene Scavenging Films Based on Ecofriendly Plastic Materials and Nano-TiO2: Preparation, Characterization, and In Vivo Evaluation.

It is known that ethylene plays an important role in the quality characteristics of fruits, especially in storage. To avoid the deterioration of fruits caused by ethylene, titanium dioxide (TiO2) has been used due to its photocatalytic capacity. The aim of this study was to develop films based on two types of biopolymers, Mater-Bi (MB) and poly-lactic acid (PLA), with nanoparticles of TiO2 and to determine their ethylene removal capacity and its application in bananas. First, the films were fabricated through an extrusion process with two different concentrations of TiO2 (5 and 10% w/w). Then, the films were characterized by their structural (FTIR), morphological (SEM), thermal (DSC and TGA), dynamic (DMA), barrier, and mechanical properties. The ethylene removal capacities of the samples were determined via gas chromatography and an in vivo study was also conducted with bananas for 10 days of storage. Regarding the characterization of the films, it was possible to determine that there was a higher interaction between PLA with nano-TiO2 than MB; moreover, TiO2 does not agglomerate and has a larger contact surface in PLA films. Because of this, a higher ethylene removal was also shown by PLA, especially with 5% TiO2. The in vivo study also showed that the 5% TiO2 films maintained their quality characteristics during the days in storage. For these reasons, it is possible to conclude that the films have the capacity to remove ethylene. Therefore, the development of TiO2 films is an excellent alternative for the preservation of fresh fruits.

Long-term findings on working memory neural dynamics in healthcare workers after mild COVID-19.

OBJECTIVE: Understanding the long-term impact of Coronavirus Disease 2019 (COVID-19) on cognitive function, even in mild cases, is critical to the well-being of individuals, especially for healthcare workers who are at increased risk of exposure to the virus. To the best of our knowledge, the electrophysiological activity underlying cognitive functioning has not yet been explored. METHODS: Seventy-seven healthcare workers took part in the study (43 with mild infection about one year before the study and 34 uninfected). To assess cognitive status, event-related potentials (ERPs) and behavioural responses were recorded while participants performed a working memory task. RESULTS: COVID-19 participants exhibited a distinct neural pattern with lower parieto-occipital N1 amplitudes and higher frontal P2 amplitudes as compared to non-infected healthcare workers. We found no behavioural differences (reaction times and error rates) in working memory functioning between groups. CONCLUSIONS: This neural pattern suggests the presence of a decrement of processing resources linked to the encoding of sensory information (N1), followed by the enhanced of the P2 response which could be interpreted as the activation of compensation mechanism in COVID-19 participants. SIGNIFICANCE: The current findings point out that ERPs could serve as valuable neural indices for detecting distinctive patterns in working memory functioning of COVID-19 participants, even in mild cases. However, further research is required to precisely ascertain the long-term cognitive effects of COVID-19 beyond one-year post-infection.

Conditioned Pain Modulation and Temporal Summation of Pain in Patients With Traumatic and Non-Specific Neck Pain: A Systematic Review and Meta-Analysis.

In patients with neck pain, it is unclear whether pain inhibition and facilitation endogenous pain mechanisms are altered. This systematic review and meta-analysis aimed to improve their understanding by assessing conditioned pain modulation (CPM) and temporal summation of pain (TSP) in patients with neck pain associated with whiplash-associated disorders (WAD) or of a nonspecific neck pain (NSNP) nature compared to pain-free controls. Very low certainty evidence suggests: impaired CPM when assessed remotely in chronic WAD patients (n = 7, 230 patients and 204 controls, standardized mean differences (SMD) = -.47 [-.89 to -.04]; P = .04) but not locally (n = 6, 155 patients and 150 controls; SMD = -.34 [-.68 to .01]; P = .05), impaired CPM in chronic NSNP patients when assessed locally (n = 5, 223 patients and 162 controls; SMD = -.55 [-1.04 to -.06]; P = .04) but not remotely (n = 3, 72 patients and 66 controls; SMD = -.33 [-.92 to .25]; P = .13), TSP not facilitated in either chronic WAD (local TSP: n = 4, 90 patients and 87 controls; SMD = .68 [-.62 to 1.99]) (remote TSP: n = 8, 254 patients and 214 controls; SMD = .18 [-.12 to .48]) or chronic NSNP (local TSP: n = 2, 139 patients and 92 controls; SMD = .21 [-1.00 to 1.41]), (remote TSP: n = 3; 91 patients and 352 controls; SMD = .60 [-1.33 to 2.52]). The evidence is very uncertain whether CPM is impaired and TSP facilitated in patients with WAD and NSNP. PERSPECTIVE: This review and meta-analysis present the current evidence on CPM and TSP in patients with WAD and NSNP. Standardization of measurement methodology is needed to draw clear conclusions. Subsequently, future studies should investigate the clinical relevance of these measurements as prognostic variables or predictors of treatment success.

Conditioned pain modulation and psychological factors in young adults with recurrent or chronic neck pain.

BACKGROUND: Controversy exists with the presence of alterations in descending pain inhibition mechanisms in patients with non-specific neck pain (NSNP). The aim of the present study was to evaluate the status of conditioned pain modulation CPM, remote pressure pain thresholds (PPT), and psychological factors in a specific subgroup of patients with NSNP such as young adult students. In addition, possible associations between CPM, psychological factors, and pain characteristics were analyzed. METHODS: Thirty students with recurrent or chronic NSNP and 30 pain-free students were included in this cross-sectional study. The following measures were assessed: CPM, remote PPT, psychological factors (depression, anxiety, pain catastrophizing, and kinesiophobia), pain characteristics (duration, intensity, severity of chronic pain, interference with daily life), and central sensitization inventory (CSI). RESULTS: No significant differences were found in the efficacy of CPM between students with chronic or recurrent NSNP and pain-free students (ß coefficient = -0.67; 95% CI = -1.54, 0.20). However, students with pain showed a significantly higher remote PPT (mean difference = -1.94; 95% CI = -2.71, -1.18). and a greater presence of anxious (mean difference = 6; 95% CI = 2, 9) and depressive symptoms (mean difference = 8.57; 95% CI = 3.97, 13.16). In addition, significant moderate or strong correlations were found between CPM and pain intensity (partial r = 0.41), pain catastrophizing and mean pain intensity (r = 0.37), grade (r = 0.50), and interference of pain (r = 0.57), kinesiophobia and disability (r = 0.38), and depression and CSI (r = 0.39). CONCLUSIONS: Young adult students with chronic or recurrent NSNP present remote hyperalgesia and symptoms of depression and anxiety but not dysfunctional CPM.

Unveiling the Role of Contingent Negative Variation (CNV) in Migraine: A Review of Electrophysiological Studies in Adults and Children.

Migraine has been considered a chronic neuronal-based pain disorder characterized by the presence of cortical hyperexcitability. The Contingent Negative Variation (CNV) is the most explored electrophysiological index in migraine. However, the findings show inconsistencies regarding its functional significance. To address this, we conducted a review in both adults and children with migraine without aura to gain a deeper understanding of it and to derive clinical implications. The literature search was conducted in the PubMed, SCOPUS and PsycINFO databases until September 2022m and 34 articles were retrieved and considered relevant for further analysis. The main results in adults showed higher CNV amplitudes (with no habituation) in migraine patients. Electrophysiological abnormalities, particularly focused on the early CNV subcomponent (eCNV), were especially prominent a few days before the onset of a migraine attack, normalizing during and after the attack. We also explored various modulatory factors, including pharmacological treatments-CNV amplitude was lower after the intake of drugs targeting neural hyperexcitability-and other factors such as psychological, hormonal or genetic/familial influences on CNV. Although similar patterns were found in children, the evidence is particularly scarce and less consistent, likely due to the brain's maturation process during childhood. As the first review exploring the relationship between CNV and migraine, this study supports the role of the CNV as a potential neural marker for migraine pathophysiology and the prediction of pain attacks. The importance of further exploring the relationship between this neurophysiological index and childhood migraine is critical for identifying potential therapeutic targets for managing migraine symptoms during its development.

Neural mechanisms underlying attentional bias modification in fibromyalgia patients: a double-blind ERP study.

There is a growing interest in the potential benefits of attentional bias modification (ABM) training in chronic pain patients. However, studies examining the effectiveness of ABM programs in fibromyalgia patients have demonstrated inconclusive effects on both behavioral indices and clinical symptoms. Additionally, underlying neural dynamics of ABM effects could yield new insights but remain yet unexplored. Current study, therefore, aims to investigate the effects of ABM training on known neural electrophysiological indicators of attentional bias to pain (P2, N2a). Thirty-two fibromyalgia patients were enrolled and randomly assigned to an ABM training (N = 16) or control (N = 16) condition (2 weeks duration). Within the ABM training condition participants performed five sessions consisting of a modified version of the dot-probe task in which patients were trained to avoid facial pain expressions, whereas in the control group participants performed five sessions consisting of a standard version of the dot-probe task. Potential ABM training effects were evaluated by comparing a single pre- and post-treatment session, in which event-related potentials (ERPs) were recorded in response to both facial expressions and target stimuli. Furthermore, patients filled out a series of self-report questionnaires assessing anxiety, depression, pain-related worrying, fear of pain, fatigue and pain status. After training, results indicated an overall reduction of the amplitude of the P2 component followed by an enhancement of N2a amplitude for the ABM condition compared to control condition. In addition, scores on anxiety and depression decreased in patients assigned to the training condition. However, we found no effects derived from the training on pain-related and fatigue status. Present study offers new insights related to the possible neural mechanisms underlying the effect of ABM training in fibromyalgia. Clinical trial (TRN: NCT05905159) retrospectively registered (30/05/2023).

Study of Ethylene-Removing Materials Based on Eco-Friendly Composites with Nano-TiO2.

Ethylene is a phytohormone that is responsible of fruit and vegetable ripening. TiO2 has been studied as a possible solution to slowing down unwanted ripening processes, due to its photocatalytic capacity which enables it to remove ethylene. Thus, the objective of this study was to develop nanocomposites based on two types of eco-friendly materials: Mater-Bi® (MB) and poly(lactic acid) (PLA) combined with nano-TiO2 for ethylene removal and to determine their ethylene-removal capacity. First, a physical-chemical characterization of nano-TiO2 of different particle sizes (15, 21, 40 and 100 nm) was done through structural and morphological analysis (DRX, FTIR and TEM). Then, its photocatalytic activity and the ethylene-removal capacity were determined, evaluating the effects of time and the type of light irradiation. With respect to the analysis of TiO2 nanoparticles, the whole samples had an anatase structure. According to the photocatalytic activity, nanoparticles of 21 nm showed the highest activity against ethylene (~73%). The results also showed significant differences in ethylene-removal activity when comparing particle size and type and radiation time. Thus, 21 nm nano-TiO2 was used to produce nanocomposites through the melt-extrusion process to simulate industrial processing conditions. With respect to the nanocomposites' ethylene-removing properties, there were significant differences between TiO2 concentrations, with samples with 5% of active showed the highest activity (~57%). The results obtained are promising and new studies are needed to focus on changes in material format and the evaluation in ethylene-sensitive fruits.

Wild Asparagus Shoots Constitute a Healthy Source of Bioactive Compounds.

Wild Asparagus shoots are consumed worldwide, although most species remain understudied. In this work, a total of four wild Asparagus species were collected from different locations and analyzed compared with farmed A. officinalis. Shoots were screened for (i) phenolic compounds by HPLC-DAD and LC-MS; (ii) total phenolic acids and total flavonoid content by the Folin-Ciocalteu and aluminum chloride methods; (iii) vitamin C by HPLC-DAD; (iv) antioxidant activity by the DPPH and ABTS•+ methods; and (v) the in vitro antiproliferative activities against HT-29 colorectal cancer cells by the MTT assay. Phenolics ranged from 107.5 (A. aphyllus) to 605.4 mg/100 g dry weight (dw) (A. horridus). Vitamin C ranged from 15.8 (A. acutifolius) to 22.7 mg/100 g fresh weight (fw) (A. officinalis). The antioxidant activity was similar in all species, standing out in A. officinalis with 5.94 (DPPH) and 4.64 (ABTS) mmol TE/100 g dw. Among phenolics, rutin reached the highest values (574 mg/100 g dw in A. officinalis), followed by quercetin, nicotiflorin, asterin, and narcissin. The MTT assay revealed the inhibitory effects of ethanol extracts against HT-29 cancer cells, highlighting the cell growth inhibition exercised by A. albus (300 µg/mL after 72 h exposure to cells). This work improves knowledge on the phytochemicals and bioactivities of the shoots of wild Asparagus species and confirms their suitability for use as functional foods.

COVID-19 inactivated and non-replicating viral vector vaccines induce regulatory training phenotype in human monocytes under epigenetic control.

Background: Trained immunity is the enhanced innate immune response resulting from exposure to pathogens or vaccines against an unrelated pathogen stimulus. Certain vaccines induce a memory like response in monocytes and NK cells, leading to modulation in cytokine production, metabolic changes, and modifications in histone patterns. Here, we hypothesized that vaccination against SARS-CoV-2 could induce the training of monocytes in addition to stimulating the adaptive immune response. Methods: Therefore, we aimed to investigate the immunophenotyping, cytokine and metabolic profile of monocytes from individuals who were completely immunized with two doses of inactivated COVID-19 vaccine or non-replicating viral vector vaccine. Subsequently, we investigated the epigenetic mechanisms underlying monocyte immune training. As a model of inflammatorychallenge, to understand if the monocytes were trained by vaccination and how they were trained, cells were stimulated in vitro with the endotoxin LPS, an unrelated stimulus that would provoke the effects of training. Results: When challenged in vitro, monocytes from vaccinated individuals produced less TNF-α and those who received inactivated vaccine produced less IL-6, whereas vaccination with non-replicating viral vector vaccine induced more IL-10. Inactivated vaccine increased classical monocyte frequency, and both groups showed higher CD163 expression, a hallmark of trained immunity. We observed increased expression of genes involved in glycolysis and reduced IRG1 expression in vaccinated subjects, a gene associated with the tolerance phenotype in monocytes. We observed that both vaccines reduced the chromatin accessibility of genes associated with the inflammatory response, the inactivated COVID-19 vaccine trained monocytes to a regulatory phenotype mediated by histone modifications in the IL6 and IL10 genes, while the non-replicating viral vector COVID-19 vaccine trained monocytes to a regulatory phenotype, mediated by histone modifications in the IL6, IL10, TNF, and CCL2 genes. Conclusions: Our findings support the recognized importance of adopting vaccination against SARS CoV-2, which has been shown to be effective in enhancing the adaptive immune response against the virus and reducing mortality and morbidity rates. Here, we provide evidence that vaccination also modulates the innate immune response by controlling the detrimental inflammatory response to unrelated pathogen stimulation.

Development and Evaluation of the Properties of Active Films for High-Fat Fruit and Vegetable Packaging.

ß-cyclodextrin and allyl isothiocyanate inclusion complexes (ß-CD:AITC) have been proposed for developing fresh fruit and vegetable packaging materials. Therefore, the aim of this research was to develop active materials based on poly(lactic acid) (PLA) loaded with ß-CD:AITC and to assess changes in the material properties during the release of AITC to food simulants. PLA films with 0, 5 and 10 wt.% ß-CD:AITC were developed by extrusion. Surface properties were determined from contact angle measurements. Films were immersed in water, aqueous and fatty simulants to assess the absorption capacity and the change in the thermal properties. Moreover, the release of AITC in both simulants was evaluated by UV-spectroscopy and kinetic parameters were determined by data modeling. Results showed that a higher concentration of ß-CD:AITC increased the absorption of aqueous simulant of films, favoring the plasticization of PLA. However, the incorporation of ß-CD:AITC also avoided the swelling of PLA in fatty simulant. These effects and complex relationships between the polymer, inclusion complexes and food simulant explained the non-systematic behavior in the diffusion coefficient. However, the lower partition coefficient and higher percentage of released AITC to the fatty simulant suggested the potential of these materials for high-fat fruit and vegetable active packaging applications.

Spinal dopaminergic D1-and D2-like receptors have a sex-dependent effect in an experimental model of fibromyalgia.

There is evidence about the importance of sex in pain. The purpose of this study was to investigate the effect of sex in the antiallodynic activity of spinal dopamine D1-and D2-like receptors in a model of fibromyalgia-type pain in rats. Reserpine induced the same extent of tactile allodynia in female and male rats. Intrathecal injection of SCH-23390 (3-30 nmol, D1-like receptor antagonist), pramipexole (0.15-15 nmol) or quinpirole (1-10 nmol D2-like receptor agonists) increased withdrawal threshold in reserpine-treated female rats. Those drugs induced a greater antiallodynic effect in female rats. Sex-difference was also observed in a nerve injury model. Ovariectomy abated the antiallodynic effect of SCH-23390 (30 nmol) in reserpine-treated rats, while systemic reconstitution of 17ß-estradiol levels or intrathecal injection of estrogen receptor-α agonist protopanaxatriol in ovariectomized reserpine-treated females restored the antiallodynic effect of SCH-23390. Intrathecal administration of ICI-182,780 (estrogen receptor-α/ß antagonist) or methyl-piperidino-pyrazole hydrate (estrogen receptor-α antagonist) abated 17ß-estradiol-restored antiallodynic effect of SCH-23390 in rats. In contrast, ovariectomy slightly reduced the effect of pramipexole (15 nmol) or quinpirole (10 nmol) in reserpine-treated rats, whereas systemic reconstitution of 17ß-estradiol levels did not modify the antiallodynic effect of both drugs. Combination 17ß-estradiol/progesterone, but not 17ß-estradiol nor progesterone alone, restored the antiallodynic effect of pramipexole and quinpirole in the rats. Mifepristone (progesterone receptor antagonist) abated 17ß-estradiol + progesterone restoration of the antiallodynic effect of pramipexole and quinpirole. These data suggest that the antiallodynic effect of dopamine D1-and D2-like receptors in fibromyalgia-type pain depends on spinal 17ß-estradiol/estrogen receptor-α and progesterone receptors, respectively.

Current evidence and clinical utility of phenobarbital for alcohol withdrawal syndrome.

BACKGROUND: Phenobarbital (PB) has been acknowledged among clinicians as a potential alternative to benzodiazepines (BZD) to decrease the need for hospital length of stay and complications associated with alcohol withdrawal syndrome (AWS). However, the level of evidence, including appropriate dosing, is unclear. We aim to summarize the evidence regarding PB used in AWS and provide future agendas for research. METHODS: Following the PRISMA guidelines, we searched MEDLINE, EMBASE, ClinicalTrials.gov, and WHO ICTRP for all peer-reviewed articles and clinical trials using keywords including"alcohol withdrawal", "delirium tremens", "phenobarbital," and "barbiturate" from their inception to September 18, 2022. RESULTS: We included 20 articles, nine in the emergency department (ED) and 11 in the general floors or intensive care units (ICUs). Studies performed in the ED included two RCTs, although both suffered from a considerably small sample size. Six studies done in the general floors or ICUs compared PB and BZD monotherapy, while four compared the utility of adjunct PB in addition to BZD compared with BZD monotherapy and one was a database study without specific dosing information. Overall, there was considerable heterogeneity in PB dosing, measured outcomes, and AWS severity measurement scales. CONCLUSION: This systematic review summarizes the current evidence related to PB use in AWS. While considerable heterogeneity exists among studies available, PB as monotherapy without BZD may be a safe and effective alternative in AWS treatment. Future prospective studies or trials should focus on the standardization of PB dosing and outcomes.

Spinal dopaminergic D1 and D5 receptors contribute to reserpine-induced fibromyalgia-like pain in rats.

Fibromyalgia is a complex pain syndrome without a precise etiology. Reduced monoamines levels in serum and cerebrospinal fluid in fibromyalgia patients has been reported and could lead to a dysfunction of descending pain modulatory system producing the painful syndrome. This study evaluated the role of D1-like dopamine receptors in the reserpine-induced fibromyalgia-like pain model in female Wistar rats. Reserpine-treated animals were intrathecally injected with different dopamine receptors agonists and antagonists, and small interfering RNAs (siRNAs) against D1 and D5 receptor subtypes. Withdrawal and muscle pressure thresholds were assessed with von Frey filaments and the Randall-Selitto test, respectively. Expression of D1-like receptors in lumbar spinal cord and dorsal root ganglion was determined using real time polymerase chain reaction (qPCR). Reserpine induced tactile allodynia and muscle hyperalgesia. Intrathecal dopamine and D1-like receptor agonist SKF-38393 induced nociceptive hypersensitivity in naïve rats, whilst this effect was prevented by the D1-like receptor antagonist SCH-23390. Moreover, SCH-23390 induced a sex-dependent antiallodynic effect in reserpine-treated rats. Furthermore, transient silencing of D1 and D5 receptors significantly reduced reserpine-induced hypersensitivity in female rats. Reserpine slightly increased mRNA D5 receptor expression in dorsal spinal cord, but not in DRG. This work provides new insights about the involvement of the spinal dopaminergic D1/D5 receptors in reserpine-induced hypersensitivity in rats.

Pain E-motion Faces Database (PEMF): Pain-related micro-clips for emotion research.

A large number of publications have focused on the study of pain expressions. Despite the growing knowledge, the availability of pain-related face databases is still very scarce compared with other emotional facial expressions. The Pain E-Motion Faces Database (PEMF) is a new open-access database currently consisting of 272 micro-clips of 68 different identities. Each model displays one neutral expression and three pain-related facial expressions: posed, spontaneous-algometer and spontaneous-CO2 laser. Normative ratings of pain intensity, valence and arousal were provided by students of three different European universities. Six independent coders carried out a coding process on the facial stimuli based on the Facial Action Coding System (FACS), in which ratings of intensity of pain, valence and arousal were computed for each type of facial expression. Gender and age effects of models across each type of micro-clip were also analysed. Additionally, participants' ability to discriminate the veracity of pain-related facial expressions (i.e., spontaneous vs posed) was explored. Finally, a series of ANOVAs were carried out to test the presence of other basic emotions and common facial action unit (AU) patterns. The main results revealed that posed facial expressions received higher ratings of pain intensity, more negative valence and higher arousal compared with spontaneous pain-related and neutral faces. No differential effects of model gender were found. Participants were unable to accurately discriminate whether a given pain-related face represented spontaneous or posed pain. PEMF thus constitutes a large open-source and reliable set of dynamic pain expressions useful for designing experimental studies focused on pain processes.

Working memory dysfunction in fibromyalgia is associated with genotypes of the catechol- O-methyltransferase gene: an event-related potential study.

Recent findings have associated different COMT genotypes with working memory capacity in patients with fibromyalgia. Although it is thought that the COMT gene may influence neural correlates (P2 and P3 ERP components) underlying working memory impairment in this chronic-pain syndrome, it has not yet been explored. Therefore, the aim of the present research was to investigate the potential effect of the COMT gene in fibromyalgia patients on ERP working memory indices (P2 and P3 components). For this purpose, 102 participants (51 patients and 51 healthy control participants) took part in the experiment. Event-related potentials and behavioral responses were recorded while participants performed a spatial n-back task. Participants had to decide if the stimulus coincided or not in the same location as the one presented one (1-back condition) or two (2-back condition) trials before. Genotypes of the COMT gene were determined through a saliva sample from all participants. Present results significantly showed lower working memory performance (p < 0.05) in patients with fibromyalgia as compared to control participants (higher rate of errors and slower reaction times). At neural level, we found that patients exhibited enhanced frontocentral and parieto-occipital P2 amplitudes compared to control participants (p < 0.05). Interestingly, we also observed that only fibromyalgia patients carrying the Val/Val genotype of the COMT gene showed higher frontocentral P2 amplitudes than control participants (p < 0.05). Current results (behavioral outcomes and P2 amplitudes) confirmed the presence of an alteration in working memory functioning in fibromyalgia. The enhancement of frontocentral P2 could be reflecting that these patients would manifest an inefficient way of activating executive attention processes, in carriers of the Val/Val genotype of COMT. To our knowledge, the present findings are the first linking neural indices of working memory dysfunctions and COMT genotypes in fibromyalgia. Applying a subgroup of patient's strategy based on this genetic marker could be useful to establish more tailored therapeutical approaches.

Electrophysiological indices of pain expectation abnormalities in fibromyalgia patients.

Fibromyalgia is a chronic pain syndrome characterized by dysfunctional processing of nociceptive stimulation. Neuroimaging studies have pointed out that pain-related network functioning seems to be altered in these patients. It is thought that this clinical symptomatology may be maintained or even strengthened because of an enhanced expectancy for painful stimuli or its forthcoming appearance. However, neural electrophysiological correlates associated with such attentional mechanisms have been scarcely explored. In the current study, expectancy processes of upcoming laser stimulation (painful and non-painful) and its further processing were explored by event-related potentials (ERPs). Nineteen fibromyalgia patients and twenty healthy control volunteers took part in the experiment. Behavioral measures (reaction times and subjective pain perception) were also collected. We manipulated the pain/no pain expectancy through an S1-S2 paradigm (cue-target). S1 (image: triangle or square) predicted the S2 appearance (laser stimulation: warmth or pinprick sensation). Laser stimuli were delivered using a CO2 laser device. Temporal and spatial principal component analyses were employed to define and quantify the ERP component reliability. Statistical analyses revealed the existence of an abnormal pattern of pain expectancy in patients with fibromyalgia. Specifically, our results showed attenuated amplitudes at posterior lCNV component in anticipation of painful stimulation that was not found in healthy participants. In contrast, although larger P2 amplitudes to painful compared to innocuous events were shown, patients did not show any amplitude change in this laser-evoked response as a function of pain predictive cues (as occurred in the healthy control group). Additionally, analyses of the subjective perception of pain and reaction time indicated that laser stimuli preceded by pain cues were rated as more painful than those signaling non-pain expectancy and were associated with faster responses. Differences between groups were not found. The present findings suggest the presence of dysfunction in pain expectation mechanisms in fibromyalgia that eventually may make it difficult for patients to correctly interpret signs that prevent pain symptoms. Furthermore, the abnormal pattern in pain expectancy displayed by fibromyalgia patients could result in ineffective pain coping strategies. Understanding the neural correlates of pain processing and its modulatory factors is crucial to identify treatments for chronic pain syndromes.

Neural correlates of the attentional bias towards pain-related faces in fibromyalgia patients: An ERP study using a dot-probe task.

BACKGROUND: One of the major cognitive deficits in fibromyalgia has been linked to the hypervigilance phenomenon. It is mainly reflected as a negative bias for allocating attentional resources towards both threatening and pain-related information. Although the interest in its study has recently grown, the neural temporal dynamics of the attentional bias in fibromyalgia still remains an open question. METHOD: Fifty participants (25 fibromyalgia patients and 25 healthy control subjects) performed a dot-probe task. Two types of facial expressions (pain-related and neutral) were employed as signal stimuli. Then, as a target stimulus, a single dot replaced the location of one of these two faces. Event-related potentials (ERP) in response to facial expressions and target stimulation (i.e., dot) were recorded. Reaction time (RT) and accuracy measures in the experimental task were collected as behavioural outcomes. RESULTS: Temporal dynamics of brain electrical activity were analysed on two ERP components (P2 and N2a) sensitive to the facial expressions meaning. Pain-related faces elicited higher frontal P2 amplitudes than neutral faces for the whole sample. Interestingly, an interaction effect between group and facial expressions was also found showing that pain-related faces elicited enhanced P2 amplitudes (at fronto-central regions, in this case) compared to neutral faces only when the group of patients was considered. Furthermore, higher P2 amplitudes were observed in response to pain-related faces in patients with fibromyalgia compared to healthy control participants. Additionally, a shorter latency of P2 (at centro-parietal regions) was also detected for pain-related facial expressions compared to neutral faces. Regarding the amplitude of N2a, it was lower for patients as compared to the control group. Non-relevant effects of the target stimulation on the ERPs were found. However, patients with fibromyalgia exhibited slower RT to locate the single dot for incongruent trials as compared to congruent and neutral trials. CONCLUSIONS: Data suggest the presence of an attentional bias in fibromyalgia that it would be followed by a deficit in the allocation of attentional resources to further process pain-related information. Altogether the current results suggest that attentional biases in fibromyalgia might be explained by automatic attentional mechanisms, which seem to be accompanied by an alteration of more strategic or controlled attentional components.

Altered Subprocesses of Working Memory in Patients with Fibromyalgia: An Event-Related Potential Study Using N-Back Task.

OBJECTIVE: Cognitive dysfunction in fibromyalgia has become a key symptom considered by patients as more disabling than pain itself. Experimental evidence from neuropsychological and neuroimaging studies indicates that such cognitive impairments are especially robust when patients need to set in motion working memory processes, suggesting the existence of an altered functioning underlying the cerebral cortices of the frontoparietal memory network. However, the temporal dynamics of working memory subprocesses have not yet been explored in fibromyalgia. SUBJECTS: Thirty-six right-handed women participated in the experiment, comprising 18 patients with fibromyalgia and 18 healthy controls. METHODS: Event-related potentials (ERPs) and behavioral responses were recorded while participants were engaged in a two-back working memory task. Principal component analyses were used to define and quantify the ERP components associated with working memory processes. RESULTS: Patients with fibromyalgia exhibited worse performance than the control group, as revealed by their number of errors in the working memory task. Moreover, both scalp parieto-occipital P2 and parieto-occipital P3 amplitudes were lower for patients than for healthy control participants. Regression analyses revealed that lower P3 amplitudes were observed in those patients with fibromyalgia reporting higher pain ratings. CONCLUSIONS: The present results suggest that both encoding of information (as reflected by P2) and subsequently context updating and replacement (as seen in lower P3 amplitudes), as a part of working memory subprocesses, are impaired in fibromyalgia. Studying the temporal dynamics of working memory through the use of ERP methodology is a helpful approach to detect specific impaired cognitive mechanisms in this chronic pain syndrome. These new data could be used to develop more specific treatments adapted for each patient.