The Role of The Rostral Ventromedial Medulla in Stress Responses.

The rostral ventromedial medulla (RVM) is a brainstem structure critical for the descending pain modulation system involved in both pain facilitation and inhibition through its projection to the spinal cord. Since the RVM is well connected with pain- and stress-engaged brain structures, such as the anterior cingulate cortex, nucleus accumbens, and amygdala, its involvement in stress responses has become a matter of great interest. While chronic stress has been proposed as a trigger of pain chronification and related psychiatric comorbidities due to maladaptive stress responses, acute stress triggers analgesia and other adaptative responses. Here we reviewed and highlighted the critical role of the RVM in stress responses, mainly in acute stress-induced analgesia (SIA) and chronic stress-induced hyperalgesia (SIH), providing insights into pain chronification processes and comorbidity between chronic pain and psychiatric disorders.

Características clínicas e epidemiológicas associadas à infecção por dengue, zika e chikungunya em Salvador, Bahia / Clinical and epidemiological characteristics associated with dengue, zika and chikungunya infection in Salvador, Bahia

INTRODUÇÃO: Dengue é endêmico no Brasil desde 1981. O primeiro caso com transmissão autóctone de infecção por vírus Chikungunya (CHIKV) no Brasil foi confirmado em 2014, chamando a atenção das autoridades sanitárias, principalmente, devido a cronificação da artralgia. A partir de 2015 a circulação do vírus Zika (ZIKV) foi confirmada no país. OBJETIVO: Investigar aspectos epidemiológicos e clínicos de pacientes com infecções por ZIKV, DENV e CHIKV, e o processo de cronificação dos sintomas articulares dos pacientes confirmados por Chikungunya. MÉTODO: De setembro de 2014 a julho de 2016 foi realizado um estudo de vigilância para doença febril, em um centro de emergência em saúde de Salvador, para identificação de pacientes com idade ≥6 meses, que referiram febre nos últimos 7 dias ou que apresentaram temperatura ≥37,8ºC durante o atendimento. Entrevistamos os pacientes para coletar dados demográficos e clínicos, e revisamos os prontuários para obter a suspeita diagnóstica. Amostras de sangue de fase aguda e convalescente foram coletadas. Realizou-se testes moleculares e sorológicos para confirmar o diagnóstico de DENV, CHIKV, ZIKV ou Flavivírus não específico. Os participantes com confirmação laboratorial para CHIKV foram acompanhados via contato telefônico, em média, um ano e cinco meses após a fase aguda da doença, a fim de investigar a evolução do quadro clínico e fatores de risco associados a cronificação da artralgia. RESULTADOS: Dos 948 participantes inclusos, 247 (26,1%) tinham evidência laboratorial de uma infecção arboviral, dos quais 224 (23,6%) eram infecções simples (DENV: 32, 3,4%; CHIKV: 159, 16,7%; ZIKV: 13, 1,4% e Flavivírus: 20, 2,1%), e 23 (2,4%) foram co-infecções (DENV / CHIKV: 13, 1,4%; FLAV / CHIKV: 9, 0,9%; e DEN / ZIKV: 1, 0,1%). Rash e prurido foram mais frequente em pacientes com infecção por ZIKV, e artralgia foi mais comum em pacientes com infecção por CHIKV. Dos 265 pacientes confirmados com infecção por CHIKV, 153 (57,7%) foram acompanhados por contato telefônico, e destes, 65 (42,5%) referiram artralgia crônica, e 47 (30,7%) estavam sintomáticos no momento do contato telefônico. Sexo feminino e idade estão associados ao risco de cronificação da artralgia. CONCLUSÃO: Nossos achados revelam um desafio para um diagnóstico clínico preciso de infecções por DENV, CHIKV e ZIKV em uma área de co-circulação, além disso, coinfecções são eventos frequentes. Destacamos a alta frequência da dor articular persistente após uma infecção por CHIKV, e o impacto da artralgia crônica nas atividades diárias e laborais dos pacientes

INTRODUCTION: Dengue has been endemic in Brazil since 1981. The first case with autochthonous transmission of Chikungunya (CHIKV) virus infection in Brazil was confirmed in 2014, drawing attention of the health authorities, especially due to arthralgia chronification. Since 2015, the circulation of Zika virus (ZIKV) was confirmed in the country. AIM: To investigate the epidemiologic and clinical aspects of patients with ZIKV, DENV and CHIKV infection and the process of chronification of the joint symptoms of the patients confirmed for Chikungunya. METHOD: From September 2014 to July 2016, a surveillance study for febrile illness was carried out at a health emergency center in Salvador, to identify patients aged ≥6 months who reported fever in the last 7 days or who presented a temperature ≥ 37.8ºC during medical care. We interviewed the patients to collect demographic and clinical data. In addition, we reviewed the medical records to have the diagnostic suspicion. Acute and convalescent phase blood samples were collected. Molecular and serological tests were performed to confirm the diagnosis of DENV, CHIKV, ZIKV or non-specific Flavivirus. Participants with laboratory confirmation for CHIKV were assisted through telephone, on average, one year and five months after the acute stage of the disease to investigate the evolution of clinical picture and risk factors associated with arthralgia chronification. RESULTS: Of the 948 participants included, 247 (26.1%) had laboratory evidence of an arboviral infection, of which 224 (23.6%) were simple infections (DENV: 32, 3.4%, CHIKV: 159, 16.7%) and 23 (2.4%) were co-infections (DENV / CHIKV: 13, 1.4%, FLAV / CHIKV: 9, 0.9%, and DEN / ZIKV: 1, 0.1%). Rash and pruritus were more frequent in patients with ZIKV infection, and arthralgia was more common in patients with CHIKV infection. From the 265 patients confirmed with CHIKV infection, 153 (57.7%) were assisted by telephone and, among them, 65 (42.5%) reported chronic arthralgia and 47 (30.7%) remained symptomatic until the moment they were contacted. Female sex and age are associated with the risk of arthralgia chronification. CONCLUSION: Our findings reveal a challenge for an accurate clinical diagnosis of DENV, CHIKV and ZIKV infections in a cocirculation area, in addition, co-infections are frequent events. We highlight the high frequency of persistent joint pain after a CHIKV infection, and the impact of chronic arthralgia on patients' daily and work activities

Freud e a Grécia antiga: uma leitura do processo de cronificação em saúde mental / Freud et l’antiquité grecque: une lecture du processus de chronicisation en santé mentale / Freud and ancient Greece: a reading of the chronification process in mental health

O presente artigo tem como objetivo examinar a discussão que se realiza no Brasil sobre uma nova forma de cronificação nos ambulatórios de saúde mental. Será destacada a tensão entre a ética do bem-estar com um saber institucional legitimado a respeito dos usuários, e a dimensão ética do bem-dizer na qual a psicanálise sustenta-se orientada pela via do desejo singular a cada sujeito. Neste percurso, será traçado um paralelo entre a tradição grega e a era moderna pelo modo como exploram a sexualidade. A psicanálise, em certa medida, retoma a antiguidade pelo valor que atribui à potência sexual, em detrimento dos objetos tomados pela pulsão.

Cet article vise à examiner la discussion qui a lieu au Brésil sur une nouvelle forme de chronicisation dans les ambulatoires de santé mentale. Il sera mis en évidence la tension entre l'éthique du bien-être avec un savoir institutionnel légitime sur les usagers, et la dimension éthique du bien-dire sur laquelle la psychanalyse se fonde orientée par le désir singulier à chaque sujet.Dans cette démarche, il va tracer un parallèle entre la tradition grecque et l'ère moderne par la façon dont elles explorent la sexualité. La psychanalyse, dans une certaine mesure, reprend l'Antiquité par la valeur qu'elle attache à la puissance sexuelle, au détriment des objets pris par la pulsion.

This article aims to examine the discussion that takes place in Brazil about a new form of chronification in mental health institutions. We will highlight the tension between the ethics of well-being with a legitimized institutional knowledge about the users, and the ethical dimension of well saying in which psychoanalysis is sustained, oriented by the singular desire in each subject. On the course of this exaination, a parallel will be drawn between the Greek and the modern tradition through the way in which sexuality is explored. Psychoanalysis, to some extent, reclaims antiquity for the value atributed to sexual potency, in detriment of objects taken by the drive.

Nucleus accumbens dopaminergic neurotransmission switches its modulatory action in chronification of inflammatory hyperalgesia.

Dopaminergic neurotransmission in the nucleus accumbens, a central component of the mesolimbic system, has been associated with acute pain modulation. As there is a transition from acute to chronic pain ('chronification'), modulatory structures may be involved in chronic pain development. Thus, this study aimed to elucidate the role of nucleus accumbens dopaminergic neurotransmission in chronification of pain. We used a rat model in which daily subcutaneous injection of prostaglandin E2 in the hindpaw for 14 days induces a long-lasting state of nociceptor sensitization that lasts for at least 30 days following the end of the treatment. Our findings demonstrated that the increase of dopamine in the nucleus accumbens by local administration of GBR12909 (0.5 nmol/0.25 µL), a dopamine reuptake inhibitor, blocked prostaglandin E2 -induced acute hyperalgesia. This blockade was prevented by a dopamine D2 receptor antagonist (raclopride, 10 nmol/0.25 µL) but not changed by a D1 receptor antagonist (SCH23390, 0.5, 3 or 10 nmol/0.25 µL), both co-administered with GBR12909 in the nucleus accumbens. In contrast, the induction of persistent hyperalgesia was facilitated by continuous infusion of GBR12909 in the nucleus accumbens (0.021 nmol/0.5 µL/h) over 7 days of prostaglandin E2 treatment. The development of persistent hyperalgesia was impaired by SCH23390 (0.125 nmol/0.5 µL/h) and raclopride (0.416 nmol/0.5 µL/h), both administered continuously in the nucleus accumbens over 7 days. Taken together, our data suggest that the chronification of pain involves the plasticity of dopaminergic neurotransmission in the nucleus accumbens, which switches its modulatory role from antinociceptive to pronociceptive.

Effect of pain chronification and chronic pain on an endogenous pain modulation circuit in rats.

We tested the hypothesis that chronic pain development (pain chronification) and ongoing chronic pain (chronic pain) reduce the activity and induce plastic changes in an endogenous analgesia circuit, the ascending nociceptive control. An important mechanism mediating this form of endogenous analgesia, referred to as capsaicin-induced analgesia, is its dependence on nucleus accumbens µ-opioid receptor mechanisms. Therefore, we also investigated whether pain chronification and chronic pain alter the requirement for nucleus accumbens µ-opioid receptor mechanisms in capsaicin-induced analgesia. We used an animal model of pain chronification in which daily subcutaneous prostaglandin E2 (PGE2) injections into the rat's hind paw for 14 days, referred to as the induction period of persistent hyperalgesia, induce a long-lasting state of nociceptor sensitization referred to as the maintenance period of persistent hyperalgesia, that lasts for at least 30 days following the cessation of the PGE2 treatment. The nociceptor hypersensitivity was measured by the shortening of the time interval for the animal to respond to a mechanical stimulation of the hind paw. We found a significant reduction in the duration of capsaicin-induced analgesia during the induction and maintenance period of persistent mechanical hyperalgesia. Intra-accumbens injection of the µ-opioid receptor selective antagonist Cys(2),Tyr(3),Orn(5),Pen(7)amide (CTOP) 10 min before the subcutaneous injection of capsaicin into the rat's fore paw blocked capsaicin-induced analgesia. Taken together, these findings indicate that pain chronification and chronic pain reduce the duration of capsaicin-induced analgesia, without affecting its dependence on nucleus accumbens µ-opioid receptor mechanisms. The attenuation of endogenous analgesia during pain chronification and chronic pain suggests that endogenous pain circuits play an important role in the development and maintenance of chronic pain.