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.

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.

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.

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.

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.

Fear of pain moderates the relationship between self-reported fatigue and methionine allele of catechol-O-methyltransferase gene in patients with fibromyalgia.

Previous research has shown a consistent association among genetic factors, psychological symptoms and pain associated with fibromyalgia. However, how these symptoms interact to moderate genetic factors in fibromyalgia has rarely been studied to date. The present research investigates whether psychological symptoms can moderate the effects of catechol-O-methyltransferase on pain and fatigue. A total of 108 women diagnosed with fibromyalgia and 77 healthy control participants took part in the study. Pain, fatigue, and psychological symptoms (anxiety, depression, pain catastrophizing, fear of pain and fear of movement) were measured by self-report questionnaires. Two types of statistical analyses were performed; the first was undertaken to explore the influences of COMT genotypes on clinical symptoms by comparing patients with fibromyalgia and healthy controls. In the second analysis, moderation analyses to explore the role of psychological symptoms as potential factors that moderate the relationship between pain/fatigue and COMT genotypes were performed. The main results indicated that patients carrying the Met/Met genotype reported significantly higher levels of fatigue than heterozygote carriers (i.e., Met/Val genotype) and higher levels of fatigue, but not significantly different, than Val homozygote carriers. Among patients with fibromyalgia carrying methionine alleles (i.e., Met/Met + Met/Val carriers), only those who scored high on medical fear of pain, experienced an intensified feeling of fatigue. Thus, the present research suggests that fear of pain, as a psychological symptom frequently described in fibromyalgia may act as a moderating factor in the relationship between the Met allele of the COMT gene and the increase or decrease in self-reported fatigue. Although further research with wider patient samples is needed to confirm the present findings, these results point out that the use of psychological interventions focused on affective symptomatology might be a useful tool to reduce the severity of fibromyalgia.

Effects of COMT Genotypes on Working Memory Performance in Fibromyalgia Patients.

Growing research has reported the presence of a clear impairment of working memory functioning in fibromyalgia. Although different genetic factors involving dopamine availability (i.e, the COMT gene) have been associated with the more severe presentation of key symptoms in fibromyalgia, scientific evidence regarding the influence of COMT genotypes on cognitive impairment in these patients is still lacking. To this end, 167 participants took part in the present investigation. Working memory performance was assessed by the application of the SST (Spatial Span Test) and LNST (Letter and Number Sequence Test) belonging to the Weschler Memory Scale III. Significant working memory impairment was shown by the fibromyalgia patients. Remarkably, our results suggest that performance according to different working memory measures might be influenced by different genotypes of the COMT gene. Specifically, fibromyalgia patients carrying the Val/Val genotype exhibited significantly worse outcomes for the span of SST backward, SST backward score, SST total score and the Working Memory Index (WMI) than the Val/Val healthy carriers. Furthermore, the Val/Val patients performed worse on the SST backward and SST score than heterozygotes. Our findings are the first to show a link between the COMT gene and working memory dysfunction in fibromyalgia, supporting the idea that higher COMT enzyme activity would contribute to more severe working memory impairment in fibromyalgia.

Subliminal emotional pictures are capable of modulating early cerebral responses to pain in fibromyalgia.

Pain experience involves a complex relationship between sensory and both emotional and cognitive factors, which appear to be mediated by different neural pathways. Previous evidence has shown that whereas conscious processing of unpleasant stimuli enhances pain perception, the influence of emotions on pain under unaware conditions is much less known. The need to better characterise the relationship between pain processing and emotional factors is crucial for dealing with chronic pain conditions. Therefore, the present study aimed to explore the neural correlates relating to the influence of visual masking emotional stimulation on the processing of painful stimuli in chronic pain patients suffering from fibromyalgia (FM). Twenty FM and 22 healthy control (HC) women participated in the study. The experimental masking paradigm consisted of a rapid succession of two types of stimuli, where a masked picture (neutral, negative or pain-related) was followed by a laser stimulus (painful or not painful). LEP activity was recorded at sixty scalp electrodes. An LEP-amplitude approach was used to quantify the main cerebral waves linked to pain response. ANOVAs indicated that the posterior regions of the P1 component were sensitive to experimental manipulation (p<0.05). Specifically, FM patients showed higher amplitudes to painful stimuli preceded by pain-related pictures compared with painful trials preceded by other emotional pictures. The FM group also showed greater amplitudes than those in the HC group in P2a and P2b waves. In addition to the scalp data, at the neural level the posterior cingulate cortex, lingual gyrus and insular cortex showed higher activation in the FM group than in the HC group. Our findings show an early cerebral modulation of pain (as reflected by the P1) in FM patients, suggesting that only pain-related information, even when it is unconsciously perceived, is capable to enhance exogenous (automatic) attention, increasing the neural activity involved in processing painful stimulation. Further research is needed to fully understand unconscious emotional influences on pain in fibromyalgia.

The European Portuguese adaptation of the Fear of Pain Questionnaire / Fear of Pain Questionnaire: adaptação para o português europeu

ABSTRACT In Portugal, it is estimated that chronic pain affects 36.7% of the population, constituting a multifactorial phenomenon with great impact at individual, family, community, and social levels. In the fear-avoidance model of pain, one of the most consistent consensual in the literature, the fear arises as one of the variables that can contribute to the development and maintenance of this condition. Thus, instruments for evaluating the fear of pain, as Fear of Pain Questionnaire (FPQ-III), may be useful in the conceptualization of the subjective experience of pain. Accordingly, this paper aims to describe the adaptation of FPQ-III for the European Portuguese. A total of 1094 participants (795 women; mean age = 25.16, SD = 7.72) completed the web based questionnaire. The results pointed to a different factor solution found in the first study of the original scale (five factors: minor pain, severe pain, medical pain, injection pain, and afflicted pain), good internal consistency (.75–.85) and good correlations (between .30 and .59) between subscales and (between .68 and .85) for the total score and subscales. Given the need to meet the various dimensions of subjective experience of pain, the Fear of Pain Questionnaire is assumed as a useful tool, in combination with other, may contribute to the evaluation and intervention procedures progressively more comprehensive and adjusted to the challenges raised with the issue of chronic pain.

RESUMO Em Portugal, estima-se que a dor crônica afete 36.7% da população, constituindo um fenômeno multifatorial com grande impacto em nível individual, familiar, comunitário e social. No modelo de medo-evitamento da dor, um dos mais consensuais na literatura, o medo surge como uma das variáveis que podem contribuir para o desenvolvimento e a manutenção dessa condição. Assim, instrumentos dedicados à avaliação do medo da dor, como o Fear of Pain Questionnaire (FPQ-III), podem ser úteis na conceitualização da experiência subjetiva de dor. Em concordância, este trabalho tem como objetivo descrever a adaptação do FPQ-III para o português europeu. Preencheram o questionário pela internet 1.094 participantes (795 mulheres; idade média = 25,16, DP = 7,72). Os resultados obtidos apontam para uma solução fatorial diferente da encontrada no primeiro estudo da escala original (cinco fatores: dor leve, intensa, médica, de injeção e aflita), uma boa consistência interna (entre .75 e .85), boas correlações entre subescalas (entre .30 e .59) e entre essas e a pontuação total (entre .68 e .85). Perante a necessidade de atender a várias dimensões da experiência subjetiva de dor, o questionário de medo da dor assume-se como uma ferramenta útil que, em combinação com outras, pode contribuir para processos de avaliação e de intervenção progressivamente mais compreensivos e ajustados aos desafios levantados pela problemática de dor crônica.

Mecanismo celular y molecular de la adicción a benzodiacepinas / Cellular and molecular mechanism of the benzodiazepines addiction

Benzodiazepines (BZD) are a group of psychiatric drugs widely prescribed since their introduction in the clinical practice in the early 60's. These drugs have a high therapeutic efficacy in the anxiety treatment. The pharmacological action of BZD at molecular level over the Central Nervous System is very well established. However, there has always been a strong concern from different health systems about the addictive effects that the BZD may cause. The aim of this article is to give a precise description about the BZD molecular mechanism of addiction that has been resolved in recent time, based on results obtained in basic research, as well provide information about the epidemiological impact of the medical use of the BZD over the population.

Las benzodiacepinas (BZD) son un grupo de psicofármacos ampliamente prescritos desde su introducción en la práctica clínica a principios de los años 1960. Estos fármacos cuentan con una alta eficacia terapéutica en el tratamiento de la ansiedad. Su mecanismo de acción sobre el Sistema Nervioso Central a nivel molecular es bien conocido, sin embargo siempre ha existido preocupación entre distintos sistemas de salud por los efectos de adicción farmacológica que provocan. El objetivo de este trabajo es abordar los resultados obtenidos recientemente en investigación básica y describir el mecanismo por el cual las benzodiacepinas producen sus efectos adictivos a nivel molecular, así como informar sobre el impacto epidemiológico que tiene su uso.

Leucine-rich repeat and immunoglobulin domain-containing protein-1 (Lrig1) negative regulatory action toward ErbB receptor tyrosine kinases is opposed by leucine-rich repeat and immunoglobulin domain-containing protein 3 (Lrig3).

Lrig1 is the founding member of the Lrig family of transmembrane leucine-rich repeat proteins, which also includes Lrig2 and Lrig3. Lrig1 is a negative regulator of oncogenic receptor tyrosine kinases, including ErbB and Met receptors, and promotes receptor degradation. Lrig1 has recently emerged as both a tumor suppressor and a key regulator of epidermal and epithelial stem cell quiescence. Despite this, little is known of the mechanisms by which Lrig1 is regulated. Lrig3 was recently reported to increase ErbB receptor expression suggesting that it may function in a manner opposite to Lrig1. In this study, we explore the interaction between Lrig1 and Lrig3 and demonstrate that Lrig1 and Lrig3 functionally oppose one another. Lrig3 opposes Lrig1 negative regulatory activity and stabilizes ErbB receptors. Conversely, Lrig1 destabilizes Lrig3, limiting Lrig3's positive effects on receptors and identifying Lrig3 as a new target of Lrig1. These studies provide new insight into the regulation of Lrig1 and uncover a complex cross-talk between Lrig1 and Lrig3.

Brain correlates of cognitive inhibition in fibromyalgia: emotional intrusion of symptom-related words.

Evidence coming from neuropsychological studies has showed the presence of cognitive alterations in fibromyalgia. Such dysfunctions are especially remarkable when the set in motion of executive control processes, such as inhibition, is required to perform successfully; however, neural data related to these mechanisms are very scarce. Present study tried to characterize cognitive inhibition mechanisms, as part of the attentional control functions, in patients with fibromyalgia. Participants (two groups: fibromyalgia patients and healthy control participants) were asked to perform in an emotional Stroop task while event-related potentials (ERP) were recorded. Four different emotional interference conditions were created: fibromyalgia symptom-related words, arousing-negative, arousing-positive and neutral words. Brain activity and behavioral data were analyzed. Principal component analyses were employed to reliably define ERP components along with a source-estimation technique. Symptom-related words elicited greater frontal P450 amplitudes and enhanced activation within right inferior frontal gyrus as compared to the rest of stimuli. This effect was only true for the fibromyalgia group. Behavioral contrasts, however, did not produce significant differences. Scalp and source estimation findings suggest the presence of a specific difficulty in cognitive inhibition in fibromyalgia patients (under conditions intimately linked with the core concerns of their disease). Data point to the involvement of right inferior frontal cortices in this inefficient mechanism, which might cause an enhanced and dysfunctional effort of processing to achieve only a comparable performance to healthy people. Implications of these results are discussed. Nevertheless, further investigations are needed to better understand dysfunctional cognition in fibromyalgia.

Procesamiento central del dolor neuropático: una aproximación integrativa / Central processing of neuropathic pain: an integrative approach

The term pain matrix refers to the structures and pathways in the central nervous system that play a role in pain processing and integration. For the last several years, our group has been studying the mechanisms that are involved in the establishment of long-term pain. Our research focus has been the study of the different nuclei and corticolimbic pathways that are involved in the affective-cognitive component of pain. In addition, we have also explored painful processes and memory. The pain matrix is constituted by the ventral tegmental area (VTA), anterior cingulate cortex (ACC), and insular cortex, among others. VTA is a predominantly dopaminergic area and has projections to ACC and the insular cortex. Stimulation of this region can reduce nociception, whereas its lesion has the opposite effect. In the ACC, it has been studied how excitatory aminoacids, such as glutamate, increase nociception while inhibitory ones decrease it. Moreover, this cortex is associated with mechanisms of pain memory. In this sense, we have seen that blocking cholinergic receptors diminishes the acquisition of pain-related memories. Nociceptive stimuli increase the expression of inhibitory muscarinic M2 receptors. In relation with insular cortex, the focus of study has been on the dopaminergic system. We have found that blocking dopaminergic D2 receptors significantly reduces neuropathic nociception. In response to an inflammatory process there is a decrease in the extracellular levels of dopamine and in the expression of mRNA for excitatory dopamine D1 receptors, while there is an increase in mRNA expression for inhibitory D2 receptors. Despite current progress in this research area, more studies are needed in order to integrate the relationship among the different neurotransmission systems. This will contribute to the proposal of novel therapeutic alternatives to the conventional treatments for pain.

El término "matriz del dolor" se refiriere a todas las estructuras y vías del Sistema Nervioso Central relacionadas con la integración del dolor. Nuestro grupo estudia desde hace varios años los principales mecanismos involucrados en el desarrollo del dolor a largo plazo. Nos hemos enfocado en el estudio de diferentes núcleos y vías cortico-límbicas que están relacionadas con la parte afectiva-cognitiva, así como en la memoria de los procesos dolorosos. Dentro de estos núcleos se encuentra el área tegmental ventral (ATV), la corteza anterior del cíngulo (CAC) y la corteza insular. El ATV es una estructura principalmente dopaminérgica con proyecciones a la CAC y a la corteza insular. Como se verá más adelante, estimular este núcleo disminuye la nocicepción, mientras que el lesionarlo, la aumenta. En la CAC se ha estudiado cómo aminoácidos excitadores como el glutamato aumentan la nocicepción y cómo, por el contrario, los aminoácidos inhibitorios como la taurina, la disminuyen. Además esta corteza está relacionada con mecanismos de memoria dolorosa. Hemos visto que el bloqueo de receptores colinérgicos disminuye la adquisición de la memoria relacionada al dolor. Además, un estímulo nociceptivo aumenta la expresión de los receptores muscarínicos inhibitorios M2. En el caso de la corteza insular, se ha estudiado principalmente el papel del sistema dopaminérgico. Hemos encontrado que el bloqueo de receptores dopaminérgicos D2 disminuye de manera significativa la nocicepción neuropática. Encontramos también que los niveles extracelulares de dopamina en esta región disminuyen a consecuencia de un proceso inflamatorio, además de que disminuye la expresión del RNAm de los receptores excitadores D1 y aumenta la de los receptores inhibidores D2. A pesar del avance que se ha obtenido en esta área de investigación, se necesitan más estudios para integrar la relación entre los diferentes sistemas de neurotransmisión y poder proponer alternativas a los tratamientos convencionales para las diferentes patologías que cursan con una experiencia dolorosa.