Sex moderates the association between quantitative sensory testing and acute and chronic pain after total knee/hip arthroplasty.

OBJECTIVES: Acute postsurgical pain (APSP) may persist over time and become chronic. Research on predictors for APSP and chronic postsurgical pain (CPSP) has produced inconsistent results. This observational study aimed to analyze psychological and psychophysical variables associated with APSP and CPSP after total knee or hip arthroplasty, and to explore the role of sex. METHODS: Assessments were conducted before surgery, 48 h, and 3 months postsurgery, including questionnaires (sociodemographic, pain related, and psychological) and quantitative sensory testing (QST). Hierarchical linear regression models analyzed potential predictors of APSP and CPSP, and moderation analyses evaluated the role of sex. RESULTS: The study included 63 participants undergoing total knee (34, 54%) or hip (29, 46%) arthroplasty. Thirty-one (49.2%) were female and 32 (50.8%) were male. APSP (48 h) was associated with impaired conditioned pain modulation (CPM) (ß = 0.301, p = 0.019). CPSP (3 months) was associated with being female (ß = 0.282, p = 0.029), longer presurgical pain duration (ß = 0.353, p = 0.006), knee arthroplasty (ß = -0.312, p = 0.015), higher APSP intensity (ß = 373, p = 0.004), and impaired CPM (ß = 0.126, p = 0.004). In multivariate analysis, these clinical variables were significant predictors of CPSP, unlike sex, and CPM (adj. R 2 = 0.349). Moderation analyses showed that wind-up ratio (WUR) was a significant predictor of APSP in men (WUR × sex: b = -1.373, p = 0.046) and CPM was a significant predictor of CPSP in women (CPM × sex: b = 1.625, p = 0.016). CONCLUSIONS: Specific QST parameters could identify patients at risk for high-intensity APSP and CPSP, with sex as a moderator. This has important clinical implications for patient care, paving the way for developing tailored preventive pain management strategies.

Evaluating E-Health Literacy, Knowledge, Attitude, and Health Online Information in Portuguese University Students: A Cross-Sectional Study.

BACKGROUND: The main objective of the present study was to assess e-health literacy in a sample of Portuguese university students and its association with the level of knowledge and seeking for COVID-19-related information. METHODS: This cross-sectional online study was conducted on Portuguese university students. All students completed a questionnaire consisting of demographic characteristics, e-health Literacy Scale (eHEALS), and a questionnaire about knowledge, attitude, and health online information seeking. RESULTS: A total of 534 students (76.8% women), with a mean age of 24.3 years old (SD = 7.8), participated in this cross-sectional study, 53.0% of students were from non-health sciences. The mean score of eHEALS literacy was 28.8 (SD = 5.6). Most students (71.1%) classified the Internet as a useful, or very useful, tool in helping them make health related decisions. The use of the Internet as a tool to research health information for a period of two or more hours (OR = 1.9; CI 95% = 1.2; 3.4), to search online for health information on professional websites (OR = 2.3; CI 95% = 1.4; 3.6), to search in official media (OR = 2.3; CI 95% = 1.4; 3.9), and to study in the field of health sciences (OR = 1.6; CI 95% = 1.1; 2.6) increased the likelihood of having sufficient e-health literacy. CONCLUSION: From a public health perspective, there is a need to develop programs that increase health literacy among university students.

Sucrose preference test: A systematic review of protocols for the assessment of anhedonia in rodents.

Anhedonia is described as a decreased ability to experience rewarding and enjoyable activities, a core symptom of major depressive disorder. The sucrose preference test (SPT) is a widely used and reliable behavioural test to assess anhedonia in rodents, based on a two-bottle choice paradigm. To date, different protocols are in use, inducing variability between researchers and hampering comparisons between studies. We performed a systematic review of the SPT protocols used in 2021 to identify the parameters in which they differ and their potential impact. We searched a total of four databases (PubMed, Scopus, Web of Science and Science Direct), from 1st January 2021 to 31st December 2021, and screened a total of 1066 articles. After screening by title and abstract, a total of 415 articles were included in this review. We extracted and analysed the different procedures used, the type of sweet solution and the habituation, deprivation, and testing protocols. The overall quality of the studies was considered very good, however, SPT protocols were extremely variable between studies with a total of 65 different habituation protocols and 104 combinations of food/water deprivation and preference testing duration. As the SPT is one of the most used tests to assess anhedonia in rodents, this work raises awareness of the great variability in SPT protocols being currently used. Furthermore, we call for standardization in the protocol used, and overall improvement of data reporting of methodologies and results, to increase the consistency between studies and allow a better comparison of results between different labs.

Comparative neurotoxicity of dietary methylmercury and waterborne inorganic mercury in fish: Evidence of optic tectum vulnerability through morphometric and histopathological assessments.

This work investigated the effects of inorganic mercury (iHg) and methylmercury (MeHg) on the fish optic tectum morphology, viz. in relation to: (i) vulnerability of specific optic tectum layers; (ii) preferential targeting of Hg forms to neurons or glial cells; (iii) comparative toxicity of iHg and MeHg in this brain area that is in the maintenance of several fish behaviors. Two experiments exposing juvenile white seabream (Diplodus sargus) to waterborne iHg [HgCl2 (2 µg L-1)] and dietary MeHg (8.7 µg g-1) were performed, comprising both exposure (7 and 14 days; E7 and E14, respectively) and post-exposure (28 days; PE28) periods. Morphometric assessments were performed using stereological methods where the layers of the optic tectum were outlined, while its area and the number of neurons and glial cells were estimated. A histopathological assessment was also performed per section and per layer of optic tectum. iHg exposure did not trigger the loss of neurons during the exposure periods, while a decrease of glial cells was detected in a single layer of the optic tectum at E14. Differently, upon MeHg exposure, a decrease on the number of neurons and glial cells was found in several layers of optic tectum. In the post-exposure, both Hg forms triggered the loss of neurons, while only MeHg exposure led to a decrease on the number of glia cells. The histopathological assessment pointed out a higher toxicity of MeHg in the optic tectum layers, particularly in the post-exposure period, while no significant alterations were found in fish exposed to iHg. Hg forms targeted preferentially neurons. iHg and MeHg are relevant neurotoxicants to fish, with MeHg exposure leading to a higher toxicity than iHg in the optic tectum. After 28 days of post-exposure, iHg and MeHg neurotoxicity remained prominent, suggesting long-term effects of these toxicants.

Injection of kaolin/carrageenan in the rat knee joint induces progressive experimental knee osteoarthritis.

ABSTRACT: Osteoarthritis (OA), the most common joint disorder worldwide, is characterized by progressive degeneration of articular and periarticular structures, leading to physical and emotional impairments that greatly affect the quality of life of patients. Unfortunately, no therapy has been able to halt the progression of the disease. Owing to the complexity of OA, most animal models are only able to mimic a specific stage or feature of the human disorder. In this work, we demonstrate the intraarticular injection of kaolin or carrageenan leads to the progressive degeneration of the rat's knee joint, accompanied by mechanical hyperalgesia and allodynia, gait impairments (reduced contact area of the affected limb), and radiological and histopathological findings concomitant with the development of human grade 4 OA. In addition, animals also display emotional impairments 4 weeks after induction, namely, anxious and depressive-like behaviour, important and common comorbidities of human OA patients. Overall, prolonging kaolin or carrageenan-induced monoarthritis mimics several important physical and psychological features of human OA in both male and female rodents and could be further applied in long-term studies of OA-associated chronic pain.

Impact of the COVID-19 pandemic on the mental and physical health and overall wellbeing of university students in Portugal.

Throughout the pandemic of COVID-19 caused by SARS-CoV-2, university students were considered a vulnerable risk group for mental health impairment and wellbeing deterioration. This study aimed at evaluating the pandemic's impact on the physical and mental health and wellbeing among students of a Portuguese university. This cross-sectional study included 913 participants and ran from June to October 2020. Data collected included sociodemographics, three mental health self-report questionnaires (Depression Anxiety Stress Scale, Eating Disorder Examination Questionnaire and Brief COPE) and lifestyle practices (eating and sleeping patterns, media, and entertainment habits) during the first months of the pandemic, which included a 72-day full national lockdown. Descriptive and correlational statistical analysis were conducted. Students' food habits changed during the pandemic, namely on the consumption of snacks and fast food and, overall, less balanced meals became more prevalent. Additionally, almost 70% of the students reported Body Mass Index changes, while 59% went through sleep pattern changes-these were more pronounced in women and younger students. Over half (67%) of the inquirees exhibited an increase in their stress, depression, and generalized anxiety symptoms. Also, the study demonstrates that students' lifestyles trended negatively during the pandemic and highlights how important regular psychological, health monitoring and emotional support is, amongst this somehow overlooked population throughout the pandemic. Universities should provide support to overcome challenges in future stressful situations. This study might have an impact on how universities and higher education systems approach their students in terms of mental and physical health monitoring and promotion in future situations, non-related with COVID. Moreover, it has a large sample of students well characterized in terms of mental and physical health, which might be of interest for future comparison with other worldwide group of students throughout stressful situations, such as tragic events, wars, pandemics.

Chronic pain causes Tau-mediated hippocampal pathology and memory deficits.

Persistent pain has been recently suggested as a risk factor for dementia. Indeed, chronic pain is frequently accompanied by maladaptive brain plasticity and cognitive deficits whose molecular underpinnings are poorly understood. Despite the emerging role of Tau as a key regulator of neuronal plasticity and pathology in diverse brain disorders, the role of Tau has never been studied in the context of chronic pain. Using a peripheral (sciatic) neuropathy to model chronic pain in mice-spared nerve injury (SNI) for 4 months-in wildtype as well as P301L-Tau transgenic mice, we hereby demonstrate that SNI triggers AD-related neuropathology characterized by Tau hyperphosphorylation, accumulation, and aggregation in hippocampus followed by neuronal atrophy and memory deficits. Molecular analysis suggests that SNI inhibits autophagy and reduces levels of the Rab35, a regulator of Tau degradation while overexpression of Rab35 or treatment with the analgesic drug gabapentin reverted the above molecular changes leading to neurostructural and memory recovery. Interestingly, genetic ablation of Tau blocks the establishment of SNI-induced hippocampal morphofunctional deficits supporting the mediating role of Tau in SNI-evoked hippocampal pathology and memory impairment. These findings reveal that exposure to chronic pain triggers Tau-related neuropathology and may be relevant for understanding how chronic pain precipitates memory loss leading to dementia.

Sucrose intake and preference by Wistar Han rats are not influenced by sex or food/water deprivation.

Anhedonia is the decreased ability to experience pleasure from rewarding or enjoyable activities, a core symptom of depression. The sucrose preference test (SPT), based on a two-bottle choice paradigm, is a widely used behavioural paradigm for the evaluation of anhedonia in rodents. Up to now, different protocols have been reported regarding water/food deprivation and duration of exposure to the water/sucrose solutions. In this work, by comparing six of the most used SPT protocols regarding sucrose preference and total intake, in both male and female Wistar Han rats, we showed (i) food/water deprivation does not significantly impact sucrose intake and preference; (ii) increasing the duration of the test is associated with an increased sucrose preference and (iii) no sex-specific differences in the basal sucrose preference of Wistar Han rats. Our results call for standardization of protocols and suggest a protocol without food/water deprivation and a 12-hour duration (lights out) as more efficacious in the measurement of anhedonia in rodents. This protocol not only reduces the confounding factors of drinking patterns and the stress-inducing food/water deprivation but also is not sensitive to sex-specific differences in the total intake of liquid in Wistar Han rats.

A New Gal in Town: A Systematic Review of the Role of Galanin and Its Receptors in Experimental Pain.

Galanin is a neuropeptide expressed in a small percentage of sensory neurons of the dorsal root ganglia and the superficial lamina of the dorsal horn of the spinal cord. In this work, we systematically reviewed the literature regarding the role of galanin and its receptors in nociception at the spinal and supraspinal levels, as well as in chronic pain conditions. The literature search was performed in PubMed, Web of Science, Scopus, ScienceDirect, OVID, TRIP, and EMBASE using "Galanin" AND "pain" as keywords. Of the 1379 papers that were retrieved in the initial search, we included a total of 141 papers in this review. Using the ARRIVE guidelines, we verified that 89.1% of the works were of good or moderate quality. Galanin shows a differential role in pain, depending on the pain state, site of action, and concentration. Under normal settings, galanin can modulate nociceptive processing through both a pro- and anti-nociceptive action, in a dose-dependent manner. This peptide also plays a key role in chronic pain conditions and its antinociceptive action at both a spinal and supraspinal level is enhanced, reducing animals' hypersensitivity to both mechanical and thermal stimulation. Our results highlight galanin and its receptors as potential therapeutic targets in pain conditions.

Predictive value of quantitative sensory testing for acute and chronic postsurgical pain after total joint arthroplasty: a systematic review.

ABSTRACT: Quantitative sensory testing (QST) can be useful to identify high-risk patients for the development of chronic postsurgical pain. This systematic review aims to assess if presurgical sensory sensitivity measured using QST is associated with acute and chronic postsurgical pain after total joint arthroplasty. A systematic search was performed in September 2020 in PubMed, EMBASE, Web of Science, and Scopus, using terms related to total joint arthroplasty and QST. Prospective studies were included if they reported an association between presurgical QST and postsurgical pain in adults with osteoarthritis undergoing primary unilateral total joint arthroplasty. From 2994 identified studies, 18 met the inclusion criteria (1869 patients). Total knee arthroplasty was the most common surgery (16 studies), and pressure pain threshold was the most common test (11 studies), followed by dynamic measures (9 studies). Postsurgical pain was assessed at acute (5 studies), subacute (2 studies), and chronic (13 studies) time points. Risk of bias was assessed using the Quality in Prognosis Studies tool and evaluated as low to moderate in most domains. Fourteen studies reported at least one statistically significant association between QST and pain (acute: 4 studies, subacute: 1 study, and chronic: 9 studies). Pressure pain threshold was associated with postsurgical pain in 6 studies (of 11, 55%), heat pain threshold in 2 studies (of 6, 33%), conditioned pain modulation in 1 study (of 6, 17%), and temporal summation of pain in 5 studies (of 8, 63%). The predictive role of presurgical QST for postarthroplasty pain remains unclear, mainly because of heterogeneous methodologies and inconsistent results.

Effectiveness of hypnosis for pain and health-related quality-of-life among people with hemophilia: Three-month outcomes of a randomized controlled pilot trial.

BACKGROUND AND PURPOSE: Pain is a common condition among people with hemophilia (PWH), negatively impacting quality of life. However, effective treatment remains a challenge. This two-arm, parallel randomized controlled pilot trial aimed to examine the three-month effects of hypnosis intervention on clinical and psychosocial variables, and on the inflammatory profile of PWH. MATERIALS AND METHODS: The study was conducted between January and October 2018, in a Reference Center for Congenital Coagulopathies. Adult (age ≥18) patients were randomized to experimental group (EG) or control group (CG). The EG received four weekly hypnosis sessions plus treatment-as-usual, and the CG maintained treatment-as-usual only. Outcomes were evaluated at one week and three months post-intervention and included pain, joint status, health-related quality of life (HRQoL), emotional state and inflammatory profile (leukocytes, C-reactive protein, cytokines). The randomization sequence was computer-generated, and allocation was concealed until enrolment. The outcome assessor was blind to allocation, but blinding of the participants was not possible due to the differences in procedure. RESULTS: Twenty patients were randomized to EG (n = 10; 8 analyzed) or CG (n = 10; 10 analyzed). Two-way mixed ANOVA showed significant time × group interactions on pain interference with normal work and with relations with other people, and on perception of health status. The EG significantly improved in pain interference with normal work and perception of health status. There was no report of harm. CONCLUSION: Hypnosis may be a promising intervention to manage hemophilia-related pain and promote HRQoL, with benefits lasting up to three months.

A biocompatible and injectable hydrogel to boost the efficacy of stem cells in neurodegenerative diseases treatment.

AIMS: Stem cell therapies emerged as treatment modalities with potential to cure neurodegenerative diseases (NDs). However, despite high expectations, their clinical use is still limited. Critical issues in treatment outcomes may be related to stem cells formulation and administration route. We develop a hydrogel as a cell carrier, consisting of compounds (phospholipids and hyaluronic acid-HA) naturally present in the central nervous system (CNS). The HA-based hydrogel physically crosslinked with liposomes is designed for direct injection into the CNS to significantly increase the bone marrow mesenchymal stem cells (BMSCs) bioavailability. MATERIALS AND METHODS: Hydrogel compatibility is confirmed in vitro with BMSCs and in vivo through its intracerebroventricular injection in rats. To assess its efficacy, the main cause of chronic neurologic disability in young adults is selected, namely multiple sclerosis (MS). The efficacy of the developed formulation containing a lower number of cells than previously reported is demonstrated using an experimental autoimmune encephalomyelitis (EAE) rat model. KEY FINDINGS: The distribution of the engineered hydrogel into corpus callosum can be ideal for NDs treatment, since damage of this white matter structure is responsible for important neuronal deficits. Moreover, the BMSCs-laden hydrogel significantly decreases disease severity and maximum clinical score and eliminated the relapse. SIGNIFICANCE: The engineering of advanced therapies using this natural carrier can result in efficacious treatments for MS and related debilitating conditions.

Correlation between pain severity and levels of anxiety and depression in osteoarthritis patients: a systematic review and meta-analysis.

OBJECTIVES: Osteoarthritis (OA) is a chronic degenerative musculoskeletal disease that causes articular damage and chronic pain, with a prevalence of up to 50% in individuals >60 years of age. Patients suffering from chronic painful conditions, including OA, also frequently report anxiety or depression. A systematic review and meta-analysis were performed to assess the correlation between pain severity and depressive and anxious symptomatology in OA patients. METHODS: A systematic search was conducted using four databases (PubMed, Medline, Scopus, and Web of Science) from inception up to 14 January 2020. We included original articles evaluating pain severity and anxiety and/or depression severity in OA-diagnosed patients. Detailed data were extracted from each study, including patients' characteristics and pain, anxiety, and depression severity. When available, the Pearson correlation coefficient between pain and depression severity and pain and anxiety severity was collected, and a meta-analysis of random effects was applied. RESULTS: This systematic review included 121 studies, with a total of 38 085 participants. The mean age was 64.3 years old, and the subjects were predominantly female (63%). The most-used scale to evaluate pain severity was the Western Ontario and the McMaster Universities Osteoarthritis Index, while for anxiety and depression, the Hospital Anxiety and Depression Scale was the most used. The meta-analysis showed a moderate positive correlation between pain severity and both anxious (r = 0.31, P <0.001) and depressive symptomatology (r = 0.36, P <0.001). CONCLUSION: Our results demonstrate a significant correlation between pain and depression/anxiety severity in OA patients, highlighting the need for its routine evaluation by clinicians.

Prevalence and Interference of Chronic Pain Among People With Hemophilia: A Systematic Review and Meta-Analysis.

Chronic pain is a common condition among people with hemophilia (PWH), associated with joint deterioration due to repeated joint bleeds. This systematic review and meta-analysis aimed to determine the prevalence of chronic pain due to haemophilia and to analyze its interference in the lives of patients. A systematic search was performed in May and June 2019 and updated in February 2021, using PubMed, EMBASE, Web of Science and SciElo. The search included terms related to hemophilia, pain, pain prevalence and pain interference. Studies were included if they reported data referring to hemophilia-related chronic pain among adult males (age ≥18). From 3,258 identified studies, 11 met the inclusion criteria. Three studies used a proposed definition for hemophilia-related chronic pain and 8 used direct questions developed by the authors. For the global samples, prevalence ranged from 17% to 84%. The random-effects meta-analysis including all studies demonstrated a pooled prevalence of chronic pain of 46% (95% Confidence Interval, CI = 34%-58%). Subgroup analysis of samples including all disease severities or including only severe patients revealed a pooled prevalence of 48% (95% CI = 29%-67%) and 53% (95% CI = 38%-69%), respectively. High heterogeneity between studies was observed in all models. Information concerning chronic pain interference was retrieved from 1 study, reporting a mean interference of 3.7 (0-10 numerical rating scale from the Brief Pain Inventory). This systematic review revealed a wide prevalence range of hemophilia-related chronic pain across studies, varying methodologies and sample characteristics. Research in the hemophilia field should clearly distinguish between acute and chronic pain and provide complete characterization of study samples. PERSPECTIVE: Pain is a central issue in the lives of people with hemophilia, posing a significant challenge for healthcare providers. A clear picture of chronic pain due to hemophilia is precluded by high heterogeneity among studies and various definitions used to investigate its prevalence.

Modulating inflammation through the neutralization of Interleukin-6 and tumor necrosis factor-α by biofunctionalized nanoparticles.

Biological agents that neutralize the activity of pro-inflammatory cytokines are revolutionizing the treatment of inflammatory conditions. However, the antibodies (Abs) short half-life and off-target distribution critically limit their efficacy and safety. Therefore, this work proposes the immobilization of anti-TNF-α and anti-IL-6 Abs at the surface of polymeric nanoparticles (NPs) in order to extend and increase the Abs therapeutic efficacy, owing to the protection from degradation that the NPs provide, and to avoid off-target side effects through local administration. In an in vitro model of inflammation, biofunctionalized NPs were able to reduce the harmful effects on human chondrocytes provided by inflammatory macrophages, being demonstrated the additive effects of the dual neutralization. Significantly, biofunctionalized NPs ameliorated inflammation more efficiently than soluble Abs in an in vivo experimental model of inflammation, exhibiting a safe profile, a prolonged action, and a stronger efficacy. Hence, as this strategy is able to increase the therapeutic efficacy of the currently available treatments, it is a promising potential therapeutic option for inflammatory conditions.

Chronic pain susceptibility is associated with anhedonic behavior and alterations in the accumbal ubiquitin-proteasome system.

ABSTRACT: It remains unknown why on similar acute/subacute painful conditions, pain persists in some individuals while in others it resolves. Genetic factors, mood, and functional alterations, particularly involving the mesolimbic network, seem to be key. To explore potential susceptibility or resistance factors, we screened a large population of rats with a peripheral neuropathy and we isolated a small subset (<15%) that presented high thresholds (HTs) to mechanical allodynia (reduced pain manifestation). The phenotype was sustained over 12 weeks and was associated with higher hedonic behavior when compared with low-threshold (LT) subjects. The nucleus accumbens of HT and LT animals were isolated for proteomic analysis by Sequential Window Acquisition of All Theoretical Mass Spectra. Two hundred seventy-nine proteins displayed different expression between LT and HT animals or subjects. Among several protein families, the proteasome pathway repeatedly emerged in gene ontology enrichment and KEGG analyses. Several alpha and beta 20S proteasome subunits were increased in LT animals when compared with HT animals (eg, PSMα1, PSMα2, and PSMß5). On the contrary, UBA6, an upstream ubiquitin-activating enzyme, was decreased in LT animals. Altogether these observations are consistent with an overactivation of the accumbal proteasome pathway in animals that manifest pain and depressive-like behaviors after a neuropathic injury. All the proteomic data are available through ProteomeXchange with identifier PXD022478.

Nociceptive, emotional, electrophysiological, and histological characterization of the chronic constriction injury model in female Wistar Han rats.

Chronic neuropathic pain affects 7-10 % of the population and is often accompanied by comorbid emotional disorders, which greatly reduce the quality of life of the patients, impairing physical, cognitive, emotional, and social functioning. Despite the higher prevalence and severity of chronic pain in women, the number of publications using female animals remains scarce. While in the chronic constriction injury (CCI) model the development of mechanical/thermal hyperalgesia, allodynia and spontaneous pain has been shown in both sexes, little is known on CCI-induced emotional impairments and sciatic nerve histopathology in female rats, as well as on the contributions of ovarian hormones to peripheral nerve injury. In this work, young adult rats (Wistar Han) were assigned to one of five groups: gonadally intact females (SHAM/SHAM), ovariectomized females (SHAM/OVX), gonadally intact females with CCI (CCI/SHAM); ovariectomized females with CCI (CCI/OVX) and males with CCI (CCIM). In the postoperative period, CCI animals, both females and males, displayed visible gait abnormalities, limping and guarding the affected hind paw although locomotion was not affected. Neuropathic females developed sustained mechanical allodynia, with CCI/OVX animals displaying symptoms two weeks before CCI/SHAM females. Interestingly, regarding mechanical and cold allodynia, CCI males slowly recovered from week 3 onwards. While CCI induced neither anxiety- nor depressive-like behaviour in females, ovariectomy per se induced anhedonic-like behaviour, regardless of CCI surgery. Histopathological analysis of the sciatic nerve showed CCI induced nerve damage, fibrosis, myelin sheath degradation and inflammation. Single-cell electrophysiological data from the rostral ventromedial medulla (RVM) suggests this area is partly involved in descending facilitation associated with experimental neuropathic pain. Altogether, our findings demonstrate CCI females display distinct sensory, emotional, electrophysiological, and histopathological impairments from males, and that ovariectomy aggravates females' responses to peripheral nerve injury.

Emotional and cognitive impairments in the peripheral nerve chronic constriction injury model (CCI) of neuropathic pain: A systematic review.

BACKGROUND AND OBJECTIVE: Emotional and cognitive impairments are common comorbidities of chronic neuropathic pain that significantly impact the quality of life of patients. While the nociceptive components of the peripheral nerve chronic constriction injury (CCI) animal model have been extensively analyzed, data related to the development of mood and cognitive disorders, and especially its impact on female rats remains fragmented. We systematically reviewed the literature analyzing the methods used to induce and evaluate the development of emotional- and cognitive-like impairments and sex-specific differences in the CCI model. DATABASES AND DATA TREATMENT: We searched PubMed, Google Scholar and Web of Science from inception to September 30th, 2019, and a total of 44 papers were considered eligible for inclusion. We included animal studies assessing nociception, locomotion, anxious-like, depressive-like and cognitive behaviours after the CCI induction. RESULTS: The overall quality of the studies was considered moderate to high. Overall, the induction of CCI leads to the development of emotional impairments, namely anxiety- and depressive-like behaviours, as well as cognitive impairments. With the majority of the studies using male subjects, the lack of evidence on female animals prevents the evaluation of sex-specific differences. CONCLUSIONS: This review supports the development of an anxiodepressive-like phenotype, associated with cognitive impairments, in CCI-induced animals. These results support the use of this animal model for the study of the mechanisms underlying these comorbidities, as well as a screening tool for the development/repurposing of drugs that tackle both the neuropathy-induced nociceptive and emotional impairments, such as tricyclic antidepressants. Importantly, our review also highlights the need for studies performed in female rodents as these are almost non-existent.

[Application of the 2015 Beers Criteria Operationalized for Portugal in Institutionalized Elderly: A Cross-Sectional Study]. / Aplicação dos Critérios de Beers de 2015 Operacionalizados para Portugal em Pessoas Idosas Institucionalizadas: Um Estudo Transversal.

INTRODUCTION: The consumption of potentially inappropriate medicines is high among institutionalized elderly, predisposing to potential drug interactions, adverse drug events, risk of iatrogenic cascade, increased morbidity and mortality and health costs. Medication review is a promising strategy for therapeutic optimization, although scarcely documented in Portugal. The aim of this study was to characterize, using explicit criteria, the existence of potentially inappropriate medicines, among institutionalized elderly, and to calculate the eventual cost savings, with their discontinuation. MATERIAL AND METHODS: Descriptive and cross-sectional study conducted in three residential homes for the elderly, from different geographic regions, based on a random sample of 33 health records. In order to characterize the existence of potentially inappropriate medicines, we used the 2015 Beers criteria, revised by the American Geriatrics Society and in the Portuguese version. RESULTS: On average, 11 drugs are prescribed to elderly residents of three residential structures for the elderly. All health records contain potentially inappropriate medicines (mean 4.8 ± 2.0 per resident), with anxiolytics (17.7%), antidepressants (17.7%) and antipsychotics (15.8%) being the most prevalent. Its reduction would result in an average monthly savings of €9.6 per resident. DISCUSSION: The consumption of potentially inappropriate medicines is higher than the literature describes, and the cost of medicines is high. The involvement of nurses in the process of drug management and reconciliation, in coordination with the physician, could be an effective strategy. This is the first study using the latest Portuguese version of the Beers criteria, which makes the comparability of the results difficult. CONCLUSION: The consumption of potentially inappropriate medicines is high, which suggest the need for adoption of improvement measures.

Introdução: O consumo de medicamentos potencialmente inapropriados é elevado entre idosos institucionalizados, predispondo à ocorrência de potenciais interações medicamentosas, eventos adversos a medicação, risco de cascata iatrogénica, aumento da morbimortalidade e dos custos em saúde. A revisão da medicação é uma estratégia promissora com vista à otimização terapêutica, ainda que pouco documentada em Portugal. Este estudo pretende caraterizar, utilizando critérios explícitos, a existência de medicamentos potencialmente inapropriados, entre idosos institucionalizados, e calcular a eventual poupança, em medicamentos, com a sua supressão.Material e Métodos: Estudo descritivo e transversal, realizado em três estruturas residenciais para pessoas idosas, de regiões geográficas distintas, a partir de uma amostra aleatória de 33 processos clínicos. Para a caracterização da existência de medicamentos potencialmente inapropriados, utilizaram-se os Critérios de Beers de 2015, revistos pela American Geriatrics Society e na versão operacionalizada para Portugal.Resultados: Em média, 11 fármacos são prescritos aos idosos residentes das estruturas residenciais para pessoas idosas. Todos os processos contêm medicamentos potencialmente inapropriados (média de 4,8 ± 2,0 por residente), sendo os ansiolíticos (17,7%), antidepressivos (17,7%) e antipsicóticos (15,8%) os mais prevalentes. A sua redução resultaria numa poupança média mensal de €9,6, por residente.Discussão: O consumo de medicamentos potencialmente inapropriados é superior ao que a bibliografia descreve e o custo com os medicamentos é elevado. O envolvimento dos enfermeiros no processo de gestão e reconciliação medicamentosa, em articulação com o médico, poderá ser uma estratégia eficaz. O estudo é pioneiro na utilização da última versão portuguesa dos critérios de Beers, o que dificulta a comparabilidade dos resultados.Conclusão: O consumo de medicamentos potencialmente inapropriados é elevado, o que sugere a necessidade de adoção de medidas de melhoria.