Safety of Intranasal Insulin in Type 2 Diabetes on Systemic Insulin: A Double-Blinded Placebo-Controlled Sub-Study of Memaid Trial.

Aims: To determine safety of intranasal insulin (INI) in MemAID trial participants with diabetes treated with systemic insulins. Materials and Methods: This randomized, double-blinded trial consisted of 24-week INI or placebo treatment once daily and 24-week follow-up. Safety outcomes were: 1) Short-term effects on glycemic variability, hypoglycemic episodes on continuous glucose monitoring (CGM) at baseline and on-treatment. 2) Long-term effects on glucose metabolism and weight on INI/placebo treatment and post-treatment follow-up. Of 86 screened subjects, 14 were randomized, 9 (5 INI, 4 Placebo) completed CGM at baseline and on-treatment, and 5 (2 INI, 3 Placebo) completed treatment and follow-up. Results: INI was safe and was not associated with serious adverse events, hypoglycemic episodes or weight gain. INI administration did not acutely affect capillary glucose. Glycemic variability on CGM decreased with INI, compared to baseline. On INI treatment, there was a long-term trend toward lower HbA1c, plasma glucose and insulin. No interactions with subcutaneous insulins were observed. Conclusions: INI is safe in older people with diabetes treated with systemic insulins, and it is not associated with adverse events, hypoglycemia or weight gain. Future studies are needed to determine whether INI administration can reduce glycemic variability, improve insulin sensitivity and thus potentially lessen diabetes burden in this population.

Criterios de evaluación de nuevas tecnologías en salud que utilizan en las Instituciones Prestadoras de Servicios de Salud en Antioquia, Colombia: estudio transversal / Criteria for evaluating new health technologies used by Health Institutions in Antioquia, Colombia: Cross-sectional study / Critérios de avaliação de novas tecnologias na saúde que utilizam nas Instituições Prestadoras de Serviços de Saúde em Antioquia, Colômbia: estudo transversal

Objetivo: una tecnología médica es el conjunto de técnicas, medicamentos, equipos y procedimientos utilizados por los profesionales de la salud en la atención médica. Este estudio busca identificar los criterios de evaluación de nuevas tecnologías en salud que utilizan algunos hospitales. Metodología: estudio observacional de corte transversal. Se incluyeron todos los directores de hospitales y clínicas del departamento de Antioquia que estuvieran interesados en participar en la investigación. Se aplicó una encuesta de 21 preguntas. Resultados: el 60 % de los encuestados dio la máxima importancia a la capacidad de producción de daños en la atención de los pacientes; el 90 % tiene en cuenta el criterio de seguridad clínica (éticos y jurídicos) y el 100 % lo hace con la evaluación de costo efectividad. En cuanto al orden de relevancia para la toma de decisiones en la adquisición de nuevas tecnologías, el perfil epidemiológico institucional tuvo mayor calificación. Conclusiones: las instituciones de salud encuestadas tienen protocolos establecidos para la evaluación de tecnologías. Se identificaron los temas a los que se les da mayor priorización, como son la producción de daños a la atención de pacientes, la seguridad clínica, aspectos éticos y jurídicos, y la evaluación de costo efectividad

Introduction: A medical technology is the set of techniques, drugs, equipment, and procedures used by health professionals in the delivery of medical care. Objective: to identify the criteria for evaluating new health technologies used by some hospitals. Methodology: An observational cross-sectional study was carried out. All the directors of Hospitals and Clinics of the department of Antioquia who belonged to one and who were interested in participating in the research were included. A survey of 21 questions was applied. Results: 60 % of the respondents gave the maximum importance to the capacity to produce damages in the care of patients, 90 % consider the criteria of clinical, ethical, and legal safety; and 100 % do it with the evaluation of cost effectiveness. In relation to the order of relevance for decision-making in the acquisition of new health technologies, it was evidenced that the institutional epidemiological profile had a higher rating. Conclusions: The surveyed health institutions have established protocols in the evaluation of new health technologies. Likewise, the issues that are given the highest priority were identified, such as the issue of harm to patient care, clinical safety, ethical and legal aspects, and cost-effectiveness evaluation.

Objetivo: uma tecnologia médica é o conjunto de técnicas, medicamentos, equipamentose procedimentos utilizados pelos profissionais da saúde na atenção médica. Este estudobusca identificar os critérios de avaliação de novas tecnologias na saúde que utilizam alguns hospitais. Metodologia: estudo observacional de corte transversal. Se incluíram todos os diretoresde hospitais e clínicas do Departamento de Antioquia que estiveram interessados em participar na investigação. Se aplicou uma enquete de 21 perguntas. Resultados: 60 % dos entrevistados deram a máxima importância na capacidade de produção de danos na atenção dos pacientes; 90% têm em conta o critério de segurançaclínica (éticos e jurídicos) e 100% o fazem com a avaliação de custo efetividade. Enquantoà ordem de relevância para a toma de decisões na aquisição de novas tecnologias, o perfil epidemiológico institucional teve maior qualificação. Conclusões: as instituições de saúde entrevistadas têm protocolos estabelecidos para a avaliação de tecnologias. Se identificaram os temas aos quais se deve dar maior priorização, como são a produção de danos à atenção de pacientes, a segurança clínica, aspectos éticos jurídicos, a avaliação de custo efetividade.

Catalytically impaired TrpA subunit of tryptophan synthase from Chlamydia trachomatis is an allosteric regulator of TrpB.

Intracellular growth and pathogenesis of Chlamydia species is controlled by the availability of tryptophan, yet the complete biosynthetic pathway for l-Trp is absent among members of the genus. Some representatives, however, preserve genes encoding tryptophan synthase, TrpAB - a bifunctional enzyme catalyzing the last two steps in l-Trp synthesis. TrpA (subunit α) converts indole-3-glycerol phosphate into indole and glyceraldehyde-3-phosphate (α reaction). The former compound is subsequently used by TrpB (subunit ß) to produce l-Trp in the presence of l-Ser and a pyridoxal 5'-phosphate cofactor (ß reaction). Previous studies have indicated that in Chlamydia, TrpA has lost its catalytic activity yet remains associated with TrpB to support the ß reaction. Here, we provide detailed analysis of the TrpAB from C. trachomatis D/UW-3/CX, confirming that accumulation of mutations in the active site of TrpA renders it enzymatically inactive, despite the conservation of the catalytic residues. We also show that TrpA remains a functional component of the TrpAB complex, increasing the activity of TrpB by four-fold. The side chain of non-conserved ßArg267 functions as cation effector, potentially rendering the enzyme less susceptible to the solvent ion composition. The observed structural and functional changes detected herein were placed in a broader evolutionary and genomic context, allowing identification of these mutations in relation to their trp gene contexts in which they occur. Moreover, in agreement with the in vitro data, partial relaxation of purifying selection for TrpA, but not for TrpB, was detected, reinforcing a partial loss of TrpA functions during the course of evolution.

Reliability of ultrasonography to detect inflammatory lesions and structural damage in juvenile idiopathic arthritis.

BACKGROUND: Musculoskeletal Ultrasonography (MSUS) is an important tool for the clinical assessment in Juvenile Idiopathic Arthritis (JIA). The objective of this study was to evaluate the reliability of MSUS to detect elementary lesions: synovitis, tenosynovitis, cartilage damage and bone erosions in the wrist and metacarpal (MCP) joints of patients with JIA. METHODS: Thirty children in various subgroups of JIA according to ILAR criteria, were included in this cross-sectional study. Clinical data including painful, swollen and limited joints were recorded. Five rheumatologist ultrasonographers, blinded to the clinical evaluation, evaluated the presence of elementary lesions in the wrist and MCP 2 and 3 joints bilaterally. The synovitis was graded in B-Mode and Power Doppler (PD). In addition to descriptive statistics intra- and inter-observer reliability was calculated using Cohen's kappa according to Landis and Koch. RESULTS: US detected more synovitis than the clinical examination (62% vs 28%, 30% vs 23% and 22% vs 17% in the wrist, second and third MCP joints respectively). The intra-observer concordance for synovitis in all joints was excellent in B-Mode (k 0.84 .63-1.0 p = 0.001), except for MCP 2, where it was good (0.61, IC 95% .34-89, p = 0.001). For both modalities (PD, B-Mode) tenosynovitis, cartilage damage and bone erosions it was also excellent. Regarding synovitis grading the concordance was excellent for all grades (0.83-1.0, IC 95% 0.51.1.0, p = 0.001), except for grade 1 where it was good (0.61, IC 95% 0.43-.83, p = 0.001). Reliability inter-observer for grayscale synovitis (0.67-0.95, IC 95% 0.67-1.0, p = 0.001), tenosynovitis grayscale (0.89, IC 95% 0.78-0.99, p.001), damage cartilage (0.89, IC 95% 0.78-0.99, p = 0.001), PD (0.66, IC 95% 0.39-1.0, p = 0.001). The concordance for grading synovitis was excellent, but for grayscale grade 1 and 2 (.66, IC 95% .53-.74, p = 0.007) and PD grade 1 and 2 (0.63, IC 95% .58-.91, p = 004) was good. CONCLUSIONS: The intra- and inter-observer reliability of MSUS for inflammatory and structural lesions is good to excellent for the wrist and MCP in patients with JIA.

Resonant magneto-acoustic switching: influence of Rayleigh wave frequency and wavevector.

We show on in-plane magnetized thin films that magnetization can be switched efficiently by 180 degrees using large amplitude Rayleigh waves travelling along the hard or easy magnetic axis. Large characteristic filament-like domains are formed in the latter case. Micromagnetic simulations clearly confirm that this multi-domain configuration is compatible with a resonant precessional mechanism. The reversed domains are in both geometries several hundreds of [Formula: see text], much larger than has been shown using spin transfer torque- or field-driven precessional switching. We show that surface acoustic waves can travel at least 1 mm before addressing a given area, and can interfere to create magnetic stripes that can be positioned with a sub-micronic precision.

Basal ganglia dysfunction in complex regional pain syndrome - A valid hypothesis?

Complex regional pain syndrome (CRPS) is a poorly understood pain disorder of the limbs. Maladaptive cortical plasticity has been shown to play a major role in its pathophysiological presentation. Recently, there is increasing interest in the role of the basal ganglia (BG), since clinical findings and neuroimaging studies point to possible BG involvement in CRPS. CRPS symptoms are often characterized by movement disorders associated with BG dysfunction. Very frequently, dystonia and tremor are reported and, to a lesser extent, myoclonus. Neuroimaging studies present inconsistent findings concerning altered brain networks and mainly focus on cortical areas. Subcortical contribution to this disorder has so far been neglected. Clinical data presenting BG dysfunction-related movement disorders in CRPS patients raise the hypothesis of BG dysfunction in this syndrome. Moreover, several neuroimaging studies documented abnormalities in the BG and in the frontal, parietal and limbic cortical areas. These regions are functionally and anatomically connected in motor, pain and working memory networks. Put together, these findings call for further characterization of the dynamic cortical and subcortical interactions in CRPS. SIGNIFICANCE: This paper presents an overview of our current knowledge about BG pathology in CRPS. A better understanding of the involvement of the BG in the CRPS pathology holds the potential for developing and improving efficacious, mechanism-based treatment modalities.

La evaluación de nuevas tecnologías en salud en hospitales: revisión narrativa / Assessment of new health technology in hospitals: Narrative review / A avaliação de novas tecnologias em saúde em hospitais: revisão narrativa

La rápida evolución de la tecnología y con ella la de los diferentes métodos diagnósticos y terapéuticos ha traído consigo un creciente interés por los profesionales de la salud en disponer de los últimos avances y las mejores tecnologías para atender a los pacientes puesto que, a través de estos recursos, se espera reducir la incertidumbre clínica en cuanto a los diagnósticos y tratamientos. Se reconoce que los avances tecnológicos son, en parte, responsables de mejorar la salud de las comunidades y, en consecuencia, de aumentar la expectativa de vida de la población. Sin embargo, el gran número de innovaciones emergentes hace pensar que debe haber un proceso de selección apropiado por parte de los sistemas de salud para garantizar que se logren en la práctica los beneficios y los propósitos planteados. La selección de las nuevas tecnologías debe incluir tanto el análisis de la tecnología en sí como la comparación con otras; este proceso se denomina Evaluación de tecnologías en salud y tiene un enfoque principalmente macro, es decir, desde agencias de evaluación de carácter nacional que evalúan con el objetivo de regular las inclusiones de tecnologías en los sistemas de salud en Colombia. Se trata de un Plan de beneficios; sin embargo, la disponibilidad de las nuevas tecnologías está en las instituciones de salud e implica una evaluación que regule las tecnologías en este nivel. Internacionalmente esto se reconoce como Evaluación de tecnologías basada en hospitales. Este artículo hace una descripción de las evaluaciones de tecnologías, pero con énfasis en metodologías hospitalarias.

The rapid evolution of technology and subsequent growth of diagnostic and therapeutic methods has brought about a growing interest in health professionals for having the latest and best technologies to serve patients as these resources are expected to reduce clinical uncertainty regarding diagnosis and treatment. Technological advances are acknowledged in part as being responsible for the improvement in the health of communities and the increase in life expectancy of the population. However, the large number of emerging innovations suggests that health systems must implement an appropriate selection process to ensure that the benefits and objectives are in fact achieved. The selection process of new technologies should include both the analysis of the technology itself as well as how it compares to others. This process is known as health technology assessment. These evaluations focus on the macro level, mainly from national assessment agencies, which evaluate with the aim of regulating the implementation of technologies in the Colombian health systems, which is a benefit plan. However, new technologies are only available in health institutions, which involves an assessment that regulates technologies at that level and is internationally known as hospital-based health technology assessment. This document provides a description of technology assessment with an emphasis on hospital methodologies.

A rápida evolução da tecnologia e com ela a dos diferentes métodos diagnósticos e terapêuticos há traído consigo um crescente interesse pelos profissionais da saúde em dispor dos últimos avances e as melhores tecnologias para atender aos pacientes posto que, através destes recursos, se espera reduzir a incerteza clínica em quanto aos diagnósticos e tratamentos. Se reconhece que os avances tecnológicos são, em parte, responsáveis de melhorar a saúde das comunidades e, em consequência, de aumentar a expectativa de vida da população. Mas, o grande número de inovações emergentes faz pensar que deve haver um processo de seleção apropriado por parte dos sistemas de saúde para garantir que se consigam na prática os benefícios e os propósitos levantados. A seleção das novas tecnologias deve incluir tanto a análise da tecnologia em si como a comparação com outras; este processo se denomina Avaliação de tecnologias em saúde e tem um enfoque principalmente macro, ou seja, desde agências de avaliação de carácter nacional que avaliam com o objetivo de regular as inclusões de tecnologias nos sistemas de saúde na Colômbia. Se trata de um Plano de benefícios; mas, a disponibilidade das novas tecnologias está nas instituições de saúde e implica uma avaliação que regula as tecnologias neste nível. Internacionalmente isto se reconhece como Avaliação de tecnologias baseada em hospitais. Este artigo faz uma descrição das avaliações de tecnologias, mas com ênfase em metodologias hospitalares.

Reward deficiency and anti-reward in pain chronification.

Converging lines of evidence suggest that the pathophysiology of pain is mediated to a substantial degree via allostatic neuroadaptations in reward- and stress-related brain circuits. Thus, reward deficiency (RD) represents a within-system neuroadaptation to pain-induced protracted activation of the reward circuits that leads to depletion-like hypodopaminergia, clinically manifested anhedonia, and diminished motivation for natural reinforcers. Anti-reward (AR) conversely pertains to a between-systems neuroadaptation involving over-recruitment of key limbic structures (e.g., the central and basolateral amygdala nuclei, the bed nucleus of the stria terminalis, the lateral tegmental noradrenergic nuclei of the brain stem, the hippocampus and the habenula) responsible for massive outpouring of stressogenic neurochemicals (e.g., norepinephrine, corticotropin releasing factor, vasopressin, hypocretin, and substance P) giving rise to such negative affective states as anxiety, fear and depression. We propose here the Combined Reward deficiency and Anti-reward Model (CReAM), in which biopsychosocial variables modulating brain reward, motivation and stress functions can interact in a 'downward spiral' fashion to exacerbate the intensity, chronicity and comorbidities of chronic pain syndromes (i.e., pain chronification).

A 'complex' of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients.

Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC) during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired on a 3 Tesla (3 T) MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years) and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years). Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA) was performed to test for group differences for all metabolites/creatine (Cre) ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA) model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE). The 3 selected metabolite ratios were aspartate (Asp)/Cre, N-acetyl aspartate (NAA)/Cre, and glutamine (Gln)/Cre. These findings are in support of a 'complex' of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite 'complex' may confer more subtle but biological processes that are ongoing. The data also support the current theory that the migraine brain is hyperexcitable even in the interictal state.

Pain in an era of armed conflicts: Prevention and treatment for warfighters and civilian casualties.

Chronic pain is a common squealae of military- and terror-related injuries. While its pathophysiology has not yet been fully elucidated, it may be potentially related to premorbid neuropsychobiological status, as well as to the type of injury and to the neural alterations that it may evoke. Accordingly, optimized approaches for wounded individuals should integrate primary, secondary and tertiary prevention in the form of thorough evaluation of risk factors along with specific interventions to contravene and mitigate the ensuing chronicity. Thus, Premorbid Events phase may encompass assessments of psychological and neurobiological vulnerability factors in conjunction with fostering preparedness and resilience in both military and civilian populations at risk. Injuries per se phase calls for immediate treatment of acute pain in the field by pharmacological agents that spare and even enhance coping and adaptive capabilities. The key objective of the Post Injury Events is to prevent and/or reverse maladaptive peripheral- and central neural system's processes that mediate transformation of acute to chronic pain and to incorporate timely interventions for concomitant mental health problems including post-traumatic stress disorder and addiction We suggest that the proposed continuum of care may avert more disability and suffering than the currently employed less integrated strategies. While the requirements of the armed forces present a pressing need for this integrated continuum and a framework in which it can be most readily implemented, this approach may be also instrumental for the care of civilian casualties.

Triptans disrupt brain networks and promote stress-induced CSD-like responses in cortical and subcortical areas.

A number of drugs, including triptans, promote migraine chronification in susceptible individuals. In rats, a period of triptan administration over 7 days can produce "latent sensitization" (14 days after discontinuation of drug) demonstrated as enhanced sensitivity to presumed migraine triggers such as environmental stress and lowered threshold for electrically induced cortical spreading depression (CSD). Here we have used fMRI to evaluate the early changes in brain networks at day 7 of sumatriptan administration that may induce latent sensitization as well as the potential response to stress. After continuous infusion of sumatriptan, rats were scanned to measure changes in resting state networks and the response to bright light environmental stress. Rats receiving sumatriptan, but not saline infusion, showed significant differences in default mode, autonomic, basal ganglia, salience, and sensorimotor networks. Bright light stress produced CSD-like responses in sumatriptan-treated but not control rats. Our data show the first brain-related changes in a rat model of medication overuse headache and suggest that this approach could be used to evaluate the multiple brain networks involved that may promote this condition.

CNS Measures of Pain Responses Pre- and Post-Anesthetic Ketamine in a Patient with Complex Regional Pain Syndrome.

BACKGROUND: Previous reports have indicated that ketamine anesthesia may produce significant improvement if not complete recovery of patients with complex regional pain syndrome (CRPS). AIMS: Here we report on a patient who had CRPS affecting mainly the right side of her body who underwent functional magnetic resonance imaging (fMRI) scans prior to and in the months following apparent successful treatment with anesthetic doses of ketamine. MATERIALS AND METHODS: The patient underwent two imaging sessions: one during her pain state (CRPS+) and 1 month after her ketamine treatment in her pain-free state (CRPS-). Both spontaneous and evoked (brush, cold, and heat) pain scores decreased from 7­9/10 on a visual analog scale prior to the treatment to 0­1 immediately following and for months after the treatment. For each imaging session, the identical mechanical (brush) and thermal (cold and heat) stimuli were applied to the same location (the skin of the dorsum of the right hand). RESULTS: Comparison of CRPS+ vs CRPS- for the three stimuli showed significant changes throughout the cerebral cortex (frontal, parietal, temporal, cingulate, and hippocampus), in subcortical regions such as caudate nucleus, and in the cerebellum. In addition, resting state network analysis showed a reversal of brain network state, and the recovered state paralleled specific default networks in healthy volunteers. DISCUSSION: The observed changes in brain response to evoked stimuli provide a readout for the subjective response. CONCLUSION: Future studies of brain function in these patients may provide novel insight into brain plasticity in response to this treatment for chronic pain.

The responsive amygdala: treatment-induced alterations in functional connectivity in pediatric complex regional pain syndrome.

The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear, and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-sex matched control subjects before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared with control subjects, with differences predominantly in the left amygdala in the pretreated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy control subjects from time 1 to time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores; and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity after an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response.

Sex and the migraine brain.

The brain responds differently to environmental and internal signals that relate to the stage of development of neural systems. While genetic and epigenetic factors contribute to a premorbid state, hormonal fluctuations in women may alter the set point of migraine. The cyclic surges of gonadal hormones may directly alter neuronal, glial and astrocyte function throughout the brain. Estrogen is mainly excitatory and progesterone inhibitory on brain neuronal systems. These changes contribute to the allostatic load of the migraine condition that most notably starts at puberty in girls.

Use of functional imaging across clinical phases in CNS drug development.

The use of novel brain biomarkers using nuclear magnetic resonance imaging holds potential of making central nervous system (CNS) drug development more efficient. By evaluating changes in brain function in the disease state or drug effects on brain function, the technology opens up the possibility of obtaining objective data on drug effects in the living awake brain. By providing objective data, imaging may improve the probability of success of identifying useful drugs to treat CNS diseases across all clinical phases (I-IV) of drug development. The evolution of functional imaging and the promise it holds to contribute to drug development will require the development of standards (including good imaging practice), but, if well integrated into drug development, functional imaging can define markers of CNS penetration, drug dosing and target engagement (even for drugs that are not amenable to positron emission tomography imaging) in phase I; differentiate objective measures of efficacy and side effects and responders vs non-responders in phase II, evaluate differences between placebo and drug in phase III trials and provide insights into disease modification in phase IV trials.

Analogous responses in the nucleus accumbens and cingulate cortex to pain onset (aversion) and offset (relief) in rats and humans.

In humans, functional magnetic resonance imaging (fMRI) activity in the anterior cingulate cortex (ACC) and the nucleus accumbens (NAc) appears to reflect affective and motivational aspects of pain. The responses of this reward-aversion circuit to relief of pain, however, have not been investigated in detail. Moreover, it is not clear whether brain processing of the affective qualities of pain in animals parallels the mechanisms observed in humans. In the present study, we analyzed fMRI blood oxygen level-dependent (BOLD) activity separately in response to an onset (aversion) and offset (reward) of a noxious heat stimulus to a dorsal part of a limb in both humans and rats. We show that pain onset results in negative activity change in the NAc and pain offset produces positive activity change in the ACC and NAc. These changes were analogous in humans and rats, suggesting that translational studies of brain circuits modulated by pain are plausible and may offer an opportunity for mechanistic investigation of pain and pain relief.

Inflaming the brain: CRPS a model disease to understand neuroimmune interactions in chronic pain.

We review current concepts in CRPS from a neuroimaging perspective and point out topics and potential mechanisms that are suitable to be investigated in the next step towards understanding the pathophysiology of CRPS. We have outlined functional aspects of the syndrome, from initiating lesion via inflammatory mechanisms to CNS change and associated sickness behavior, with current evidence for up-regulation of immunological factors in CRPS, neuroimaging of systemic inflammation, and neuroimaging findings in CRPS. The initiation, maintenances and CNS targets implicated in CRPS and in the neuro-inflammatory reflex are discussed in terms of CRPS symptoms and recent preclinical studies. Potential avenues for investigating CRPS with PET and fMRI are described, along with roles of inflammation, treatment and behavior in CRPS. It is our hope that this outline will provoke discussion and promote further empirical studies on the interactions between central and peripheral inflammatory pathways manifest in CRPS.