Mygalin, an Acanthoscurria gomesiana spider‐derived synthetic, modulates haloperidol-induced cataleptic state in mice

Background: Haloperidol (HAL) is an antipsychotic used in the treatment of schizophrenia. However, adverse effects are observed in the extrapyramidal tracts due to its systemic action. Natural compounds are among the treatment alternatives widely available in Brazilian biodiversity. Mygalin (MY), a polyamine that was synthesized from a natural molecule present in the hemolymph of the Acanthoscurria gomesian spider, may present an interesting approach. Aims: This study aimed to evaluate the effect of MY in mice subjected to HAL-induced catalepsy. Methods: Male Swiss mice were used. Catalepsy was induced by intraperitoneal administration of HAL (0.5 mg/kg − 1 mL/Kg) diluted in physiological saline. To assess the MY effects on catalepsy, mice were assigned to 4 groups: (1) physiological saline (NaCl 0.9 %); (2) MY at 0.002 mg/Kg; (3) MY at 0.02 mg/Kg; (4) MY at 0.2 mg/Kg. MY or saline was administered intraperitoneally (IP) 10 min b HAL before saline. Catalepsy was evaluated using the bar test at 15, 30, 60, 90, and 120 min after the IP administration of HAL. Results: The latency time in the bar test 15, 30, 60, and 90 min increased (p < 0.05) after IP administration of HAL compared to the control group. Catalepsy was attenuated 15, 30, 90, and 120 min (p < 0.05) after the IP-administration of MY at 0.2 mg/Kg; while MY at 0.02 mg/Kg attenuated catalepsy 15 min after the HAL treatment. Our findings showed that MY attenuates the HAL-induced cataleptic state in mice.

Acanthoscurria gomesiana spider-derived Mygalin in the prelimbic prefrontal cortex modulates neuropathic pain and depression comorbid

Depression has a high rate of comorbidity with neuropathic pain. This study aims to investigate the effect of Mygalin, an acylpolyamine synthesized from a natural molecule in the hemolymph of the Acanthoscurria gomesiana spider, injected into the prelimbic (PrL) region of the medial prefrontal cortex on chronic neuropathic pain and depression comorbidity in rats. To investigate that comorbidity, neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in male Wistar rats. The biotinylated biodextran amine (BDA) bidirectional neural tract tracer was microinjected into the PrL cortex to study brain connections. Rodents were further subjected to von Frey (mechanical allodynia), acetone (cold allodynia), and forced swim (depressive-like behavior) tests. BDA neural tract tracer-labeled perikarya were found in the dorsal columns of the periaqueductal gray matter (dPAG) and the dorsal raphe nucleus (DRN). Neuronal activity of DRN neurons decreased in CCI rats. However, PrL cortex treatment with Mygalin increased the number of spikes on DRN neurons. Mygalin treatment in the PrL cortex decreased both mechanical and cold allodynia and immobility behavior in CCI rats. PrL cortex treatment with N-methyl-D-aspartate (NMDA) receptor receptors attenuated the analgesic and antidepressive effects caused by Mygalin. The PrL cortex is connected with the dPAG and DRN, and Mygalin administration into the PrL increased the activity of DRN neurons. Mygalin in the PrL cortex produced antinociceptive and antidepressive-like effects, and the NMDA agonist reversed these effects.

Modelos neuropsicobiológicos para estudo da dor e das emoções / Neuropsychobiological models for the study of pain and emotions / Modelos neuropsicológicos para el estudio del dolor y las emociones

Dor é uma experiência pessoal e subjetiva que pode apenas ser sentida pelo sofredor. A dor aguda tem a finalidade de avisar o indivíduo que algo está errado. Contudo, a dor crônica (DC) é um problema global de saúde, que afeta a qualidade de vida e torna o indivíduo parcial ou totalmente incapacitado. A pesquisa básica utiliza diversos modelos animais para o estudo da dor aguda ou crônica, bem como para o estudo das principais comorbidades oriundas de sua cronificação como a ansiedade e a depressão. Esta revisão aborda os modelos animais mais comumente utilizados neste contexto.

Pain is a personal and subjective experience that can only be felt by the sufferer. Acute pain is intended to warn the individual that something is wrong. However, chronic pain (CP) is a global health problem, affecting the quality of life and making the individual parts or disabled. Basic research uses several animal models for the study of acute or chronic pain, as well as for the study of the main comorbidities arising from their chronicity, such as anxiety and depression. This review focuses on the animal models most commonly used in this context.

El dolor es una experiencia personal y subjetiva que solo puede sentir la víctima. El dolor agudo está destinado a advertir al individuo que algo está mal. Sin embargo, el dolor crónico (EC) es un problema de salud global, que afecta la calidad de vida y hace que el individuo esté parcial o totalmente discapacitado. La investigación básica utiliza varios modelos animales para el estudio del dolor agudo o crónico, así como para el estudio de las principales comorbilidades resultantes de su cronicidad, como la ansiedad y la depresión. Esta revisión se centra en los modelos animales más utilizados en este contexto.

The challenges of multidisciplinary treatment of post-pandemic pain caused by the Sars-CoV-2 virus / Os desafios do tratamento multidisciplinar da dor pós-pandemia ocasionada pelo vírus Sars-CoV-2

BACKGROUND AND OBJECTIVES: The International Association for the Study of Pain recommends revising the definition of pain to "An unpleasant sensory and emotional experience associated with, or similar to that associated with actual or potential tissue damage." In fact, pain is a personal experience influenced to varying degrees by biological, psychological and social factors.1 The pandemic caused by (SARS-CoV-2) exposed health professionals who were not prepared for the unprecedented challenges. Many focused on ventilators, intensive care beds, but others will remain at the forefront of pain management. The aim of this paper was to present a review of the impact of the COVID-19 pandemic on pain management, in addition to proposing an alternative to the present context, such as telerehabilitation. CONTENTS: This is an integrative review carried out on the databases: LILACS, Scielo, Pubmed, Scopus, Web of Science, PubCovid and databases dedicated to the publication of Preprints on the COVID-19 theme, such as Psyarxiv and Preprint MedRxiv. In this review we intend to highlight the cognitive, emotional and behavioral impairments related to pain during a pandemic caused by COVID-19. CONCLUSION: The pandemic context and social isolation can negatively interfere in the sensitivity responses and in the treatment of pain, either by the increase in pain events in the population, impacted by social and psychological losses or by the interruption of face-to-face care during a pandemic. At this point, we recommend a gradual advance in addressing current treatment today and propose a future roadmap to face challenges that may arise.

JUSTIFICATIVA E OBJETIVOS: A Associação Internacional para o Estudo da Dor recomendou a revisão da definição de dor para "Uma experiência sensorial e emocional desagradável associada com, ou semelhante àquela associada a dano real ou potencial do tecido". De fato, a dor é uma experiência pessoal influenciada em vários graus por fatores biológicos, psicológicos e sociais1. A pandemia provocada pela (SARS-CoV-2) expôs profissionais de saúde que não estavam preparados para os desafios sem precedentes. Muitos se concentraram em ventiladores, leitos de terapia intensiva, mas outros permaneceram na vanguarda do tratamento da dor. O objetivo deste trabalho foi apresentar uma revisão sobre o impacto da pandemia por COVID-19 no tratamento da dor, além da proposição de uma alternativa frente ao presente contexto, como a telereabilitação. CONTEÚDO: Trata-se de uma revisão integrativa realizada nas bases de dados: LILACS, Scielo, Pubmed, Scopus, Web of Science, PubCovid e bases de dados dedicadas a publicação de Preprints sobre a temática COVID-19, como Psyarxiv e Preprint MedRxiv. Na presente revisão pretendemos evidenciar os prejuízos cognitivos, emocionais e comportamentais relacionadas à dor durante a pandemia causada pela COVID-19. CONCLUSÃO: O contexto pandêmico e isolamento social pode interferir negativamente nas respostas de sensibilidade e no tratamento da dor, seja pelo aumento em eventos de dor na população, impactados pelos prejuízos sociais e psicológicos ou pela interrupção do atendimento presencial durante a pandemia. Neste ponto, recomendamos o avanço gradual na abordagem das limitações atuais do tratamento e propomos um roteiro futuro para enfrentar possíveis desafios que possam se apresentar.

Role of education after the COVID-19 pandemic fear: a multidisciplinary and scientific perspective / Papel da educação após o medo pandêmico do COVID-19: uma perspectiva multidisciplinar e científica

In response to the outbreak of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), pathogen of the new coronavirus disease (COVID-19), several sectors and social activities have been affected, including education. At first, it is explained that educators and students can feel fragile during and after the SARS-CoV-2 outbreak. Subsequently, it is discussed that their relationship ought to be carefully established given the triggering of psychological and neuropsychiatric effects arising from neural coding and plasticity processes, which result in the formation of positive and negative memories in the short to long term. Finally, it is pointed out that the SARS-CoV-2 pandemic generates a need for adequacy and adaptation for the significant attention to students during the re-starting of studies, given that possible disorders of sensory modulation and involvement of limbic brain areas triggered in situations of risk of death, potential or real threat, can happen. It is assumed that at times of the SARS-CoV-2 pandemic, in addition to preserving life, one of the challenges is the behavioural (re)organisation, which includes habits from the educational context that need to contemplate a scientific perspective, seeking to transform the consequences of the pandemic fear on opportunities to reinforcement of familiar links. In the context of modern rationality, the SARS-CoV-2 pandemic is also a period to think about the relationship between scientific knowledge and common sense. With this logic, neurosciences can develop a new format for the teaching-learning process, so that educators and students experiencing the pandemic threatening do not manifest psychological distress and secondary consequences. Therefore, education can be considered a central space in decision-making in the face of SARS-CoV-2 pandemic. In this sense, the urgency of a multidisciplinary strategies development is highlighted, connecting the synergy between neurosciences and education after the COVID-19 pandemic.

Esquizofrenia e cognição: entendendo as dimensões atencionais, perceptuais e mnemônicas da esquizofrenia / Schizophrenia and cognition: understanding the attentional, perceptual and mnemonic dimensions of schizophrenia / Esquizofrenia y cognición: comprensión de las dimensiones atencional, perceptivas y mnemotécnicas de la esquizofrenia

A esquizofrenia é um transtorno mental grave e incapacitante que tem como critérios diagnósticos sintomas positivos, negativos, discurso e pensamento desorganizado ou catatônico. Cursa com importantes disfunções cognitivas com impactos na atenção, na função executiva, em memória operacional e de trabalho, entre outras. Tais déficits podem estar presentes antes dos sintomas positivos ou mesmo, de maneira subsindrômica desde a infância desses indivíduos. A hipótese dopaminérgica é a mais aceita na gênese das disfunções neuroquímicas, mas há cada vez mais evidência do envolvimento de outros sistemas como o glutamatérgico e o serotoninérgico. No que se refere especificamente aos déficits cognitivos, destacam-se disfunções em córtex pré-frontal, especialmente sua porção dorsolateral e suas conexões com o hipocampo. Entende-se ainda que é muito importante a avaliação cognitiva das pessoas acometidas por essa patologia e existem baterias de testes neuropsicológicos disponíveis como é o caso do Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) e de testes validados no Brasil como o Brief Assessment of Cognition in Schizophrenia (BACS). Tendo em vista a elevada perda de funcionalidade e qualidade de vida desses pacientes, sobretudo daqueles mais acometidos na capacidade cognitiva, há uma necessidade de maiores esforços para o entendimento desse complexo transtorno com vistas a tratamentos mais eficazes e até mesmo desenvolvimento de estratégias preventivas.

Schizophrenia is a serious and disabling mental disorder whose diagnostic criteria are positive or negative symptoms, disorganized or catatonic speech and thinking. It takes place with important cognitive dysfunctions with impacts on attention, executive function, working memory, among others. Such deficits may be present before positive symptoms or even, in a subsyndromal manner since the childhood of these individuals. The dopaminergic hypothesis is the most accepted in the genesis of neurochemical disorders, but there is increasing evidence of the involvement of other systems such as glutamatergic and serotonergic. With regard specifically to cognitive deficits, dysfunctions in the prefrontal cortex stand out, especially its dorsolateral portion and its connections with the hippocampus. It is also understood that the cognitive test of people affected by this pathology is very important and there are neuropsychological tests batteries available, such as Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) and tests validated in Brazil such as the Brief Assessment of Cognition in Schizophrenia (BACS). Considering the high loss of functionality and life quality of these patients, especially those more affected in cognitive ability, there is a need for greater efforts to understand this complex disorder aiming more effective treatments and even the development of preventive strategies.

La esquizofrenia es un trastorno mental grave e incapacitante cuyos criterios de diagnóstico son síntomas positivos, negativos, habla y pensamiento desorganizados o catatónicos. Se lleva a cabo con importantes disfunciones cognitivas con impactos en la atención, la función ejecutiva, el trabajo y la memoria de trabajo, entre otros. Tales déficits pueden estar presentes antes de los síntomas positivos o incluso, de manera subsindrómica desde la infancia de estos individuos. La hipótesis dopaminérgica es la más aceptada en la génesis de los trastornos neuroquímicos, pero cada vez hay más evidencia de la participación de otros sistemas como el glutamatérgico y el serotoninérgico. Con respecto específicamente a los déficits cognitivos, se destacan las disfunciones en la corteza prefrontal, especialmente su porción dorsolateral y sus conexiones con el hipocampo. También se entiende que la evaluación cognitiva de las personas afectadas por esta patología es muy importante y hay baterías de pruebas neuropsicológicas disponibles, como la Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) y pruebas validadas en Brasil como el Brief Assessment of Cognition in Schizophrenia (BACS). En vista de la alta pérdida de funcionalidad y calidad de vida de estos pacientes, especialmente los más afectados por la capacidad cognitiva, existe la necesidad de realizar mayores esfuerzos para comprender este complejo trastorno con miras a tratamientos más efectivos e incluso el desarrollo de estrategias preventivas.

Connexions between the dorsomedial division of the ventromedial hypothalamus and the dorsal periaqueductal grey matter are critical in the elaboration of hypothalamically mediated panic-like behaviour.

The electrical and chemical stimulation of the dorsal periaqueductal grey matter (dPAG) elicits panic-like explosive escape behaviour. Although neurons of the ventromedial hypothalamus (VMH) seem to organise oriented escape behaviour, when stimulated with excitatory amino acids at higher doses, non-oriented/explosive escape reactions can also be displayed. The aim of this work was to examine the importance of reciprocal projections between the VMH and the dPAG for the organisation of this panic-like behaviour. The chemical stimulation of the VMH with 9nmol of N-methyl-d-aspartic acid (NMDA) elicited oriented and non-oriented escape behaviours. The pretreatment of the dPAG with a non-selective blocker of synaptic contacts, cobalt chloride (CoCl2), followed by stimulation of the dorsomedial part of the ventromedial hypothalamus (dmVMH) with 9nmol of NMDA, abolished the non-oriented/explosive escape and freezing responses elicited by the stimulation of the dmVMH. Nonetheless, the rats still showed oriented escape to the burrow. On the other hand, when the blockade of the dmVMH with CoCl2 was followed by stimulation of the dPAG with 6nmol of NMDA, no effect was observed either on the non-oriented/explosive escape or on the freezing behaviour organised by the dPAG. Furthermore, Fos protein-labelled neurons were observed in the dPAG after the stimulation of the dmVMH with 9nmol of NMDA. Additionally, when the anterograde neurotracer biotinylated dextran amine (BDA) was deposited in the dmVMH subsequent stimulation of the dmVMH produced BDA-labelled neural fibres with terminal boutons surrounding Fos-labelled neurons in the dPAG, suggesting synaptic contacts between dmVMH and dPAG neurons for eliciting panic-like behavioural responses. The current data suggest that the dPAG is the key structure that organises non-oriented/explosive escape reactions associated with panic attack-like behaviours.

Involvement of prelimbic medial prefrontal cortex in panic-like elaborated defensive behaviour and innate fear-induced antinociception elicited by GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei: role of the endocannabinoid CB1 receptor.

It has been shown that GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei (DMH and VMH, respectively) induces elaborated defensive behavioural responses accompanied by antinociception, which has been utilized as an experimental model of panic attack. Furthermore, the prelimbic (PL) division of the medial prefrontal cortex (MPFC) has been related to emotional reactions and the processing of nociceptive information. The aim of the present study was to investigate the possible involvement of the PL cortex and the participation of local cannabinoid CB1 receptors in the elaboration of panic-like reactions and in innate fear-induced antinociception. Elaborated fear-induced responses were analysed during a 10-min period in an open-field test arena. Microinjection of the GABAA receptor antagonist bicuculline into the DMH/VMH evoked panic-like behaviour and fear-induced antinociception, which was decreased by microinjection of the non-selective synaptic contact blocker cobalt chloride in the PL cortex. Moreover, microinjection of AM251 (25, 100 or 400 pmol), an endocannabinoid CB1 receptor antagonist, into the PL cortex also attenuated the defensive behavioural responses and the antinociception that follows innate fear behaviour elaborated by DMH/VMH. These data suggest that the PL cortex plays an important role in the organization of elaborated forward escape behaviour and that this cortical area is also involved in the elaboration of innate fear-induced antinociception. Additionally, CB1 receptors in the PL cortex modulate both panic-like behaviours and fear-induced antinociception elicited by disinhibition of the DMH/VMH through microinjection of bicuculline.