RESUMO
OBJECTIVE: The thermal grill illusion (TGI) in which interlacing cold and warm bars create the illusion of a painful sensation has been suggested as an experimental model for central pain states and pain processing. The aim of this study was to use this technique to gain further insights into the altered pain perception in major depressive disorder (MDD). METHODS: In 18 unmedicated patients with MDD, cold and heat pain thresholds (CPT/HPT) as well as the perception of the TGI were examined and compared with 18 matched controls. RESULTS: CPT and HPT were significantly increased in patients (7.9°C and 47.5°C) compared with controls (15.9°C and 45.2°C, respectively; p < .05). In the range of TGI stimuli that were perceived painful by controls, the patients did not indicate painful sensations, thereby indicating a shift of the stimulus-response curve of TGI pain perception toward higher stimulus intensities, that is, greater temperature differentials between cold and warm bars (11.5°C for controls, 16.7°C for patients). The patients rated the pain intensity perceived at the respective pain thresholds (CPT and HPT) in tendency higher than did the controls, whereas they perceived the TGI less painful despite increased stimulus intensities. Unpleasantness ratings were similar between groups. CONCLUSIONS: CPT, HPT and temperature differentials for the perception of the TGI, were increased in patients with MDD as compared with controls. Pain intensity, however, was rated differently for CPT and HPT, where patients indicated higher ratings in tendency, and for the TGI stimulation, where pain was perceived less intense.
Assuntos
Temperatura Baixa , Transtorno Depressivo Maior/fisiopatologia , Temperatura Alta , Ilusões/psicologia , Limiar da Dor/psicologia , Dor/fisiopatologia , Adulto , Análise de Variância , Transtorno Depressivo Maior/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/psicologia , Medição da Dor/métodos , Percepção da Dor , Sensação Térmica , Adulto JovemRESUMO
Previous studies reported increased heat pain thresholds and decreased ischemic pain thresholds in patients experiencing depression. The increased sensitivity to ischemic muscle pain was assumed to represent a model for the investigation of physical symptoms in the disease. Here, we explored how the serotonin and noradrenaline reuptake inhibitor duloxetine influences experimental pain thresholds and tolerances in depressed patients during treatment. Twenty-two patients experiencing unipolar depression were included. Pain assessments were conducted unmedicated at baseline, after 1 week, and after 6 weeks of duloxetine treatment. We observed the expected clinical response of patients indicated by a significant reduction in the Montgomery Depression Rating Scale after 6 weeks. At baseline, we found increased heat pain thresholds in patients in comparison to controls while patients simultaneously rated augmented pain perception on the visual analog scale. In contrast, patients were significantly more perceptive to ischemic muscle pain at baseline. During treatment, the examined pain thresholds showed differential changes: Increased heat pain thresholds of patients normalized during treatment, whereas no significant change was observed for ischemic pain thresholds. Thus, our results might change the view on the paradox of pain perception in major depression because increased heat pain thresholds are associated with augmented pain perception in the disease.
Assuntos
Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/psicologia , Percepção da Dor/fisiologia , Limiar da Dor/psicologia , Fenômenos Fisiológicos da Pele , Adulto , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Duloxetina , Feminino , Temperatura Alta/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Dor/complicações , Dor/tratamento farmacológico , Dor/psicologia , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Percepção da Dor/efeitos dos fármacos , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Tiofenos/uso terapêuticoRESUMO
OBJECTIVE: In addition to the sensitization of pain fibers in inflamed tissues, the increased excitability of the spinal cord is an important mechanism of inflammatory pain. Furthermore, spinal neuronal excitability has been suggested to play a role in modulating peripheral inflammation. This study was undertaken to test the hypothesis that spinal actions of the proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) add significantly to both hyperalgesia and maintenance of peripheral inflammation. METHODS: Rats with antigen-induced arthritis (AIA) were treated intrathecally with the TNFalpha-neutralizing compound etanercept continuously during the complete time course of AIA, which was 3 days for the acute phase and 21 days for the chronic phase. During this time, inflammation and pain-related behavior were monitored. Since a role for autonomic control of inflammation was proposed, measures from heart rate time series were obtained in the acute phase. Findings were compared with those in vehicle-treated animals and in animals receiving etanercept intraperitoneally. RESULTS: Spinally administered etanercept acutely reduced pain-related behavior, attenuated both the development and the maintenance of inflammation, and was superior to systemic administration. Parameters indicating autonomic modulation showed a shift toward a sympathetically dominated state in vehicle-treated animals, which was prevented by intrathecal etanercept. CONCLUSION: Our findings indicate that spinal TNFalpha plays an important role in both pain signaling and modulation of peripheral inflammation. Thus, neutralizing this cytokine at the spinal site not only represents a putative therapeutic option for different pain syndromes, but may be directly used to attenuate peripheral inflammation.
Assuntos
Antirreumáticos/farmacologia , Artrite Experimental , Hiperalgesia , Imunoglobulina G/farmacologia , Fator de Necrose Tumoral alfa , Doença Aguda , Animais , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Sistema Nervoso Autônomo/efeitos dos fármacos , Sistema Nervoso Autônomo/imunologia , Comportamento Animal/efeitos dos fármacos , Etanercepte , Feminino , Frequência Cardíaca/fisiologia , Hiperalgesia/tratamento farmacológico , Hiperalgesia/imunologia , Hiperalgesia/metabolismo , Bombas de Infusão Implantáveis , Injeções Espinhais , Articulação do Joelho/imunologia , Articulação do Joelho/metabolismo , Locomoção/efeitos dos fármacos , Dinâmica não Linear , Ratos , Ratos Endogâmicos Lew , Receptores do Fator de Necrose Tumoral , Medula Espinal/imunologia , Medula Espinal/metabolismo , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Inflammation causes sensitization of peripheral and central nociceptive neurons. Pharmacological modulation of the latter has successfully been used for clinical pain relief. In particular, inhibitors of the NMDA glutamate receptor such as ketamine and agonists at the mu-opioid receptor such as morphine are broadly used. Besides driving the propagation of pain signals, spinal mechanisms are also discussed to modulate inflammation in the periphery. Here, we tested the hypothesis that intrathecally applied ketamine or morphine not only reduce pain-related behavior, but also attenuate induction and maintenance of the inflammatory response in a model of chronic antigen-induced arthritis (AIA). Ketamine, morphine or vehicle was applied to the spinal cords of anesthesized animals with AIA. Swelling and histopathological changes were assessed after 6h (acute phase). Intrathecal catheters were implanted in another set of animals with AIA and substances were applied continuously. During the observation period of 21 days, inflammation and pain-related behavior were assessed. Ketamine and morphine significantly reduced arthritis severity as indicated by reduced joint swelling, but even more intriguingly by reduced infiltration with inflammatory cells and joint destruction in the acute and the chronic phase of arthritis. Morphine showed strong antinociceptive effects in the acute phase only, while the newly established effective dose for ketamine in a continuous application design reduced hyperalgesia in the acute and the chronic stage. In conclusion, both compounds exhibit anti-inflammatory effects during induction and maintenance of arthritis when applied intrathecally. These data thus propose a role of spinal NMDA- and opioid-receptors in the neuronal control of immune-mediated inflammation.
Assuntos
Analgésicos Opioides/farmacologia , Anestésicos Dissociativos/farmacologia , Artrite Experimental/patologia , Hiperalgesia/patologia , Ketamina/farmacologia , Morfina/farmacologia , Doenças do Sistema Nervoso Periférico/patologia , Analgésicos Opioides/administração & dosagem , Anestésicos Dissociativos/administração & dosagem , Anestésicos Dissociativos/sangue , Animais , Artrite Experimental/complicações , Doença Crônica , Feminino , Hiperalgesia/etiologia , Bombas de Infusão Implantáveis , Injeções Espinhais , Ketamina/administração & dosagem , Ketamina/sangue , Coxeadura Animal/etiologia , Coxeadura Animal/psicologia , Laminectomia , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Morfina/administração & dosagem , Medição da Dor/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/etiologia , Ratos , Ratos Endogâmicos Lew , Medula Espinal/efeitos dos fármacos , Medula Espinal/patologia , Medula Espinal/fisiologiaRESUMO
BACKGROUND: Atopic dermatitis has been shown to be associated with neurogenic and psychosocial factors. In related atopic diseases such as rhinitis or asthma, a shift in autonomic balance towards a parasympathetic modulation has been described. On the other hand, the psychiatric symptoms known for atopic dermatitis are often associated with decreased vagal modulation. Furthermore, an increased parasympathetic activity has been shown to exhibit anti-inflammatory effects, thus rather alleviating dermatitis symptoms. OBJECTIVE: In order to address these intriguing discrepancies, we aimed to assess the autonomic state in patients suffering from atopic dermatitis. METHODS: Heart rate variability assessment was performed in 30 patients and data were compared to those obtained from matched controls. Furthermore, questionnaires for disease activity and psychosocial stressors were employed. RESULTS: Patients showed higher values for parasympathetic modulation than controls. This was mainly reflected by an increase in the root mean square of successive differences (RMSSD). This parameter further correlated with dermatological symptoms and the time since the last severe exacerbation of the disease. In addition, subgroups of patients with dyshidrosis or photophobia showed significant differences in autonomic modulation under deep respiration. Moreover, cardiac autonomic modulation was hardly altered upon postural change, indicating that autonomic reactivity is only mildly influenced in these patients. CONCLUSION: Patients with atopic dermatitis showed an autonomic dysbalance which is comparable to other diseases related to atopy or allergy. Our findings point to the question whether these alterations are disease-inherent or counter-regulatory, which should be addressed in future studies.
Assuntos
Dermatite Atópica/fisiopatologia , Nervo Vago/fisiopatologia , Adulto , Sistema Nervoso Autônomo/fisiopatologia , Estudos de Casos e Controles , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Nervoso Parassimpático/fisiopatologia , Psicologia , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: Cardiac autonomic dysregulation has been reported in patients with schizophrenia. However, there are no definite data examining whether other branches of the autonomic nervous system are compromised as well and how they interrelate with cardiac function. In this study, we tested the hypothesis that the autonomic dysregulation at the heart is reflected in the regulation of the pupillary light reflex. METHODS: We assessed heart rate variability and baroreflex sensitivity parameters as well as pupillographic measures in 28 unmedicated patients with schizophrenia and compared these measures to those of 28 controls. In addition, cardiovascular and pupillographic parameters were correlated in both groups. RESULTS: The obtained cardiovascular parameters indicated decreased parasympathetic modulation. Patients showed a significantly increased resting pupil diameter as well as reduced relative amplitude, suggesting a dominance of sympathetic control and a lack of parasympathetic modulation at the pupil. Intriguingly, the parasympathetic latency of the pupil constriction was similar in both groups and correlated with several cardiovascular parameters. These correlations were in the opposite direction in patients compared to controls. Furthermore, shorter latencies of the pupil constriction were associated with symptom severity in patients. CONCLUSIONS: Overall, we found evidence for an autonomic dysregulation at the pupil and heart in patients with schizophrenia. Future studies are warranted to describe this complex interaction at different levels of the autonomic system. SIGNIFICANCE: The interrelationship of both the systems indicates that the autonomic dysfunction affects the regulation in different branches of the autonomic network as well as their interaction in schizophrenia.
Assuntos
Sistema Cardiovascular/fisiopatologia , Pupila/fisiologia , Esquizofrenia/fisiopatologia , Doença Aguda , Adolescente , Adulto , Idoso , Barorreflexo/fisiologia , Vasos Sanguíneos/fisiologia , Feminino , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pupila/efeitos da radiação , Tempo de Reação/fisiologia , Reflexo Pupilar/fisiologia , Análise de Regressão , Adulto JovemRESUMO
BACKGROUND: Chronic alcoholism represents a risk factor for cardiac arrhythmias. One underlying mechanism is a sympathetically dominated autonomic imbalance. This is especially apparent during acute withdrawal from alcohol. Since linear analysis of heart rate variability may not be entirely adequate to detect such autonomic dysfunction in acute alcohol withdrawal, we applied novel non-linear parameters and measures for cardio-respiratory coupling. METHODS: 20 patients suffering from acute alcohol withdrawal syndrome and 20 controls were included. For patients, heart rate and respiration were recorded on admission, after medication and at discharge. From these data, complexity measures (symbolic dynamics, approximate entropy) of heart rate modulation and respiration as well as parameters for cardio-respiratory coupling (coherence, cross-approximate entropy) which relate to vagal function were calculated. RESULTS: Heart rate modulation was significantly less complex in patients acutely admitted for alcohol withdrawal. Furthermore, coupling between beat-to-beat (RR) intervals and respiration time series was significantly diminished. Of the parameters assessed, cross-approximate entropy showed a trend for correlation with symptom severity. CONCLUSION: These data indicate diminished vagal function in acute alcohol withdrawal. Applying the methods described thus allows a sensitive detection of vagal neuropathy in this disease.
Assuntos
Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Depressores do Sistema Nervoso Central/efeitos adversos , Etanol/efeitos adversos , Mecânica Respiratória/efeitos dos fármacos , Síndrome de Abstinência a Substâncias/fisiopatologia , Adulto , Alcoolismo/psicologia , Algoritmos , Clormetiazol/uso terapêutico , Entropia , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipnóticos e Sedativos/uso terapêutico , Masculino , Análise Multivariada , Escalas de Graduação Psiquiátrica , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Nervo Vago/fisiopatologiaRESUMO
Disturbed autonomic nervous system (ANS) function in schizophrenia might contribute to increased cardiovascular mortality. We obtained heart rate variability indices from 40 unmedicated schizophrenic patients and 58 matched controls. Mainly we found that patients displaying stronger psychotic symptoms as assessed by the Brief Psychiatric Rating Scale exhibit more severe cardiac ANS disturbances compared with controls.
Assuntos
Doenças do Sistema Nervoso Autônomo/fisiopatologia , Coração/fisiologia , Rede Nervosa/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia Paranoide/fisiopatologia , Nervo Vago/fisiologia , Doença Aguda , Adulto , Antipsicóticos/efeitos adversos , Arritmias Cardíacas/induzido quimicamente , Doenças do Sistema Nervoso Autônomo/epidemiologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Masculino , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/epidemiologia , Esquizofrenia Paranoide/tratamento farmacológico , Esquizofrenia Paranoide/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: Recent reports suggest that vascular factors play a crucial role in the development and progression of Alzheimer's disease. We aimed to assess vasomotor reactivity in patients with Alzheimer's disease and vascular dementia due to microangiopathy using transcranial Doppler sonography and near-infrared spectroscopy during a CO(2) exposition task. METHODS: The normalized CO(2) reactivity assessed at the middle cerebral artery and the oxygenated and deoxygenated hemoglobin of the frontal cortex were obtained. To investigate the impact of cholinergic deficiency known for Alzheimer's disease on vasomotor reactivity, both groups were reinvestigated during treatment with the acetylcholine esterase inhibitor galantamine. RESULTS: Transcranial Doppler analysis revealed significantly reduced normalized CO(2) reactivity for Alzheimer's disease and vascular dementia. Vasomotor reactivity assessed by near-infrared spectroscopy was decreased in patients with vascular dementia, but not in Alzheimer's disease. Galantamine treatment showed a beneficial effect, normalizing these parameters close to age-matched control levels. CONCLUSIONS: Our results suggest that Alzheimer's disease is associated with a lack of vasomotor reactivity, which might be associated with disturbed autoregulation indicating a potential risk for a decreased protection of brain tissue against blood pressure changes. Additionally, a diminished increase of cortical oxygenated hemoglobin during the CO(2) test was apparent in patients with vascular dementia. Galantamine treatment influenced vascular reactivity in the CO(2) test, thus providing evidence for the cholinergic deficiency, thereby adding to vascular dysregulation in Alzheimer's disease, but also indicating an important role of cholinergic system dysfunction for vascular dementia.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Transtornos Cerebrovasculares/tratamento farmacológico , Demência Vascular/tratamento farmacológico , Demência Vascular/patologia , Galantamina/farmacologia , Acetilcolinesterase/metabolismo , Adulto , Idoso , Dióxido de Carbono/metabolismo , Estudos de Casos e Controles , Transtornos Cerebrovasculares/patologia , Inibidores da Colinesterase/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema Nervoso/patologia , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Ultrassonografia Doppler/métodosRESUMO
BACKGROUND: To further elucidate the close interrelation of pain and depression, we investigated cerebral responses to parametrically varied thermal pain intensities in female patients suffering from major depressive disorder (MDD) (n = 13) and matched control subjects (n = 13) by means of functional magnetic resonance imaging (fMRI). METHODS: After the assessment of the individual thermal pain threshold, an fMRI-compatible thermode was used to deliver thermal painful stimuli to the right arm. All stimuli were initiated for 10 sec from a baseline resting temperature (32 degrees C) in three different conditions (37 degrees C, 42 degrees C, 45 degrees C). Statistical Parametric Mapping 2 (SPM2) software was used for image processing and statistical analyses. RESULTS: Patients displayed significantly increased thermal pain thresholds. A comparable increase in blood oxygenation level-dependent (BOLD) signal was observed in key structures of the pain matrix in patients and control subjects. Patients displayed hyperactivation in comparison with control subjects for the painful 45 degrees C condition in the left ventrolateral thalamus, in the right ventrolateral prefrontal cortex (VLPFC) and dorsolateral prefrontal cortex (DLPFC), as well as a stronger parametric BOLD signal increase in the right VLPFC, DLPFC, and in the contralateral insula. Symptom severity correlated positively with the BOLD signal in the left ventrolateral nucleus of the thalamus. CONCLUSIONS: We present evidence that cortical structures of the pain matrix are similarly activated in depressed patients and healthy subjects. We report increased prefrontal and lateral thalamic activation during the presentation of painful stimuli, which might explain reduced thermal pain perception on the skin in depressed patients.
Assuntos
Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/psicologia , Dor/fisiopatologia , Dor/psicologia , Córtex Pré-Frontal/fisiopatologia , Adulto , Interpretação Estatística de Dados , Feminino , Temperatura Alta , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Oxigênio/sangue , Medição da Dor , Limiar da Dor/fisiologia , Percepção/fisiologia , Fenômenos Fisiológicos da PeleRESUMO
Patients with schizophrenia have been reported to experience sudden cardiac death 3 times more likely than individuals from the general population. One important factor related to an increased risk of cardiac arrhythmias and sudden death is the prolongation of the QTc interval. This study examined whether acute psychosis might influence the beat-to-beat variability of the QT interval, which reflects effectively cardiac repolarization lability. High resolution electrocardiographic recordings were performed in 25 unmedicated patients suffering from acute schizophrenia and matched controls. From these, parameters of beat-to-beat heart rate and QT variability measures such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the scale for the assessment of positive symptoms (SAPS) and negative symptoms (SANS). QTvi was significantly higher in patients with schizophrenia compared to controls. While QTvi correlated with the degree of delusions and hallucinations, no correlation with electrolyte concentrations was found. Approximate entropy of heart rate was decreased indicating reduced complexity and decreased vagal tone. In conclusion, increased QT variability in patients with schizophrenia indicates abnormal cardiac repolarization lability, which can result in serious cardiac arrhythmias. The correlation of positive symptoms with QT variability might indicate high sympathetic cardiac activity in these patients, which might be associated with increased cardiovascular mortality.
Assuntos
Eletroencefalografia/estatística & dados numéricos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/fisiopatologia , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatologia , Doença Aguda , Adulto , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/epidemiologia , Comorbidade , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Eletroencefalografia/métodos , Entropia , Feminino , Coração/inervação , Coração/fisiopatologia , Testes de Função Cardíaca , Frequência Cardíaca/fisiologia , Humanos , Síndrome do QT Longo/epidemiologia , Masculino , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Esquizofrenia/epidemiologia , Psicologia do Esquizofrênico , Nervo Vago/fisiopatologiaRESUMO
Decreased vagal activity has been described in acute schizophrenia and might be associated with altered cardiovascular regulation and increased cardiac mortality. The aim of this study was to assess baroreflex sensitivity in the context of psychopathology. Twenty-one acute, psychotic, unmedicated patients with a diagnosis of paranoid schizophrenia were investigated after admission to the hospital. Results were compared with 21 healthy volunteers matched with respect to age and sex. Cardiovascular parameters obtained included measures for heart rate variability, baroreflex sensitivity, as well as cardiac output, left ventricular work index, and total peripheral resistance. All parameters investigated were analyzed using linear and novel nonlinear techniques. Positive and negative symptoms were assessed to estimate the impact of psychopathology on autonomic parameters. Subjects with acute schizophrenia showed reduction of baroreflex sensitivity accompanied by tachycardia and greatly increased left ventricular work index. Nonlinear parameters of baroreflex sensitivity correlated with positive symptoms. For heart rate variability, mainly parameters indicating parasympathetic modulation were decreased. Vascular pathology could be excluded as a confounding factor. These results reflect a dysfunctional cardiovascular regulation in acute schizophrenic patients at rest. The changes are similar to adaptational regulatory processes following stressful mental or physical tasks in healthy subjects. This study suggests that hyperarousal in acute schizophrenia is accompanied by decreased efferent vagal activity, thus increasing the risk for cardiovascular mortality. Future studies are warranted to examine the role of the sympathetic system and possible autonomic differences in hyperarousal induced by anxiety and/or external stressful events.
Assuntos
Barorreflexo/fisiologia , Esquizofrenia Paranoide/fisiopatologia , Adulto , Pressão Sanguínea/fisiologia , Cardiografia de Impedância , Estudos de Casos e Controles , Feminino , Frequência Cardíaca/fisiologia , Humanos , MasculinoRESUMO
Complex interactions between pain perception, anxiety and depressive symptoms have repeatedly been described. However, pathophysiological or biochemical mechanisms underlying the alterations of pain perception in patients suffering from anxiety or depression still remain a matter of debate. Thus, we aimed to perform an investigation on pain perception in an animal model of extremes in anxiety-related behaviour, which might provide a tool for future studies. Here, thermal pain thresholds were obtained from rats with a genetic predisposition to high anxiety-related behaviour (HAB), including signs of comorbid depression-like behaviour and from controls (low-anxiety rats (LAB); cross-bred HAB and LAB rats; Wistar rats). Furthermore, the effect of eight-week antidepressive treatment using citalopram and of short-term anxiolytic treatment with diazepam on pain-related behaviour was assessed. Simultaneously, anxiety-related behaviour was monitored. At baseline, HAB animals showed 35% higher thresholds for thermal pain than controls. These were normalized to control levels after eight weeks of continuous citalopram treatment paralleled by a reduction of anxiety-related behaviour, but also acutely after diazepam administration. Overall, thermal pain thresholds in HAB animals are shifted in a similar fashion as seen in patients suffering from major depressive disorder. Antidepressive, as well as anxiolytic treatments, attenuated these differences. As the relative importance of the factors anxiety and depression cannot be derived from this study with certainty, extending these investigations to additional animal models might represent a valuable tool for future investigations concerning the interrelations between anxiety, depression, and pain at a molecular level.
Assuntos
Ansiolíticos/farmacologia , Antidepressivos de Segunda Geração/farmacologia , Ansiedade/tratamento farmacológico , Citalopram/farmacologia , Diazepam/farmacologia , Limiar da Dor/efeitos dos fármacos , Análise de Variância , Animais , Ansiedade/genética , Cruzamentos Genéticos , Modelos Animais de Doenças , Temperatura Alta , Masculino , Ratos , Ratos Endogâmicos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Especificidade da Espécie , Estatísticas não ParamétricasRESUMO
To assess the relative importance of the isoforms of nitric oxide synthase (NOS) in inflammatory pain, we directly compared pain behaviour and paw thickness after intraplantar injection of complete Freund's adjuvant (CFA) in wild-type (WT) mice and in mice lacking either inducible (iNOS), endothelial (eNOS) or neuronal NOS (nNOS). In mice deficient for nNOS, thermal hyperalgesia was reduced by approximately 50% compared to wild type mice at 4 and 8h after CFA injection, and mechanical hypersensitivity was absent. The only change in pain behaviour in iNOS and eNOS deficient mice compared to WT mice was a more rapid recovery from thermal hyperalgesia. A compensatory up-regulation of nNOS in dorsal root ganglia (DRG) and spinal cords of iNOS and eNOS knockout mice was excluded using RT-PCR. However, an increase of iNOS gene expression was found in spinal cords of eNOS and nNOS deficient mice. To study the downstream effects of nNOS deficiency on DRG neurones, we assessed their immunoreactivity for calcitonin gene-related peptide (CGRP) and cytokines. We found a significant reduction in the CFA induced increase in CGRP immunoreactive neurones as well as in CGRP gene expression in nNOS deficient mice, whereas the percentage of cells immunopositive for tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) was unchanged. These results support the proposed role of nNOS in sensitization of DRG neurones, and might indicate that CGRP is involved in this process.
Assuntos
Hiperalgesia/fisiopatologia , Inflamação/complicações , Óxido Nítrico Sintase/genética , Dor/fisiopatologia , Animais , Comportamento Animal , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Feminino , Adjuvante de Freund , Gânglios Espinais/enzimologia , Regulação Enzimológica da Expressão Gênica/imunologia , Hiperalgesia/imunologia , Inflamação/induzido quimicamente , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo I/genética , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo III , Dor/imunologia , Medula Espinal/enzimologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
OBJECTIVE: Cardiovascular mortality is significantly increased in patients suffering from schizophrenia. The mechanisms currently discussed contain unhealthy lifestyle with obesity and smoking, increased incidence of diabetes, adverse pro-arrhythmic effects of antipsychotic medication and altered autonomic function. It is therefore likely that the adaptation of the heart rate to different requirements is faulty in schizophrenia. One way to detect adaptive capabilities and thus stability of regulation is to measure complexity of heart rate fluctuations, with more complex heart rate fluctuations indicating better adaptability of the underlying system. METHODS: We calculated novel non-linear measures for beat-to-beat interval complexity from short-term ECG recordings in 20 unmedicated patients suffering from acute schizophrenia and compared them to those obtained from matched controls. RESULTS: Data from all mathematical models applied, i.e. joint symbolic dynamics, compression entropy, fractal dimension and approximate entropy, revealed significantly reduced complexity of heart rate time series in acute schizophrenia. When using heart rate as a covariate, only fractal dimension remained significantly altered, thus appearing to be a relatively more important heart rate independent parameter. CONCLUSIONS: Complexity of heart rate modulation is significantly reduced in acute, untreated schizophrenia, thus indicating an increased risk for cardiovascular events in these patients. SIGNIFICANCE: These data might eventually add to the currently discussed monitoring of physical health in patients with schizophrenia, possibly providing a promising tool for cardio-arrhythmic risk stratification.
Assuntos
Frequência Cardíaca , Esquizofrenia/fisiopatologia , Doença Aguda , Adaptação Fisiológica , Adulto , Análise de Variância , Doenças Cardiovasculares/mortalidade , Eletrocardiografia , Entropia , Feminino , Fractais , Humanos , Modelos Logísticos , Masculino , Modelos Cardiovasculares , Psicometria , Medição de RiscoRESUMO
OBJECTIVE: Acute alcohol withdrawal is associated with increased cardiovascular mortality, most likely due to cardiac arrhythmias. As the QT interval reflects the most critical phase for the generation of reentry and thus for arrhythmia, we examined QT variability in patients suffering from acute alcohol withdrawal. METHODS: High resolution electrocardiographic recordings were performed in 18 male unmedicated patients suffering from acute alcohol withdrawal, 18 matched controls and 15 abstained alcoholics. From these, parameters of beat-to-beat heart rate and QT variability such as approximate entropy and QT variability index (QTvi) were calculated. Measures were correlated with the severity of withdrawal symptoms and with serum electrolyte concentrations. RESULTS: Heart rate and QTvi were significantly increased in acute alcohol withdrawal. Abstained alcoholics did not significantly differ from controls. While QTvi correlated with the severity of alcohol withdrawal symptoms, the mean QT interval duration showed an inverse relationship with serum potassium concentrations. CONCLUSION: Our data indicate increased QT variability and thus increased repolarization lability in acute alcohol withdrawal. This might add to the elevated risk for serious cardiac arrhythmias. In part, these changes might be related to increased cardiac sympathetic activity or low potassium, thus suggesting the latter as possible targets for adjuvant pharmacological therapy during withdrawal.
Assuntos
Delirium por Abstinência Alcoólica/diagnóstico , Alcoolismo/reabilitação , Eletrocardiografia , Síndrome do QT Longo/diagnóstico , Adulto , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Potássio/sangue , RiscoRESUMO
An altered perception of pain has been described for several psychiatric disorders. To date the influence of adjustment disorders (AD) on pain perception has not been described. Here, we investigated perception of experimentally induced pain in 15 patients suffering from AD (subtype with depressive symptoms) and controls matched for age and sex. Thresholds and tolerances were assessed for thermal and electrical pain on both sides of the body. We found an overall increase of pain thresholds and tolerances in AD patients as compared to controls, predominately on the right side of the body. Analogue findings have been reported for pain perception in major depressive disorder (MDD). Of the data obtained, only thermal pain threshold on the right arm correlated with the severity of depressive symptoms. Although the underlying pathology is elusive it is likely that the mechanisms for reduced pain sensitivity are comparable in MDD and AD.
Assuntos
Transtornos de Adaptação/psicologia , Dor/psicologia , Adulto , Depressão/psicologia , Estimulação Elétrica , Feminino , Temperatura Alta , Humanos , Masculino , Análise Multivariada , Medição da Dor , Limiar da Dor/fisiologia , Escalas de Graduação PsiquiátricaRESUMO
Acute alcohol withdrawal is often associated with increased sympathetic activity, and a decreased baroreflex sensitivity (BRS) can be assumed. Parameters of heart rate variability (HRV), blood pressure variability (BPV), BRS as well as cardiac index (CI), left ventricular work index (LVWI) and total peripheral resistance (TPR) were investigated in 20 patients undergoing acute alcohol withdrawal and matched controls. Measures were obtained during the peak of withdrawal symptomatology prior to treatment as well as 2 and 24h under continuous clomethiazole treatment. Alcohol withdrawal scores were obtained and correlated with autonomic measures. In addition, parameters were assessed in 15 subjects who abstained from alcohol after long-term intake. We found a severe down-regulation of BRS during acute alcohol withdrawal and to a milder extent in abstained alcoholics. Furthermore, HRV and BPV did not unequivocally reveal signs of elevated sympathetic activity. Non-linear parameters of HRV and parameters of BRS correlated with the severity of AWS. The distinct decrease of BRS in AWS and in long-term abstained subjects described here is of importance since similar alterations have been identified as independent prognostic factors for cardiac mortality in other diseases.
Assuntos
Alcoolismo/reabilitação , Barorreflexo/fisiologia , Etanol/efeitos adversos , Inativação Metabólica , Reflexo Anormal/fisiologia , Síndrome de Abstinência a Substâncias/etiologia , Síndrome de Abstinência a Substâncias/fisiopatologia , Temperança , Doença Aguda , Adulto , Clormetiazol/farmacocinética , Moduladores GABAérgicos/farmacocinética , Frequência Cardíaca/fisiologia , Hospitalização , Humanos , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Masculino , Síndrome de Abstinência a Substâncias/diagnósticoRESUMO
One frequently described feature of depression is an increased vulnerability to pain complaints, and chronic pain is frequently accompanied by symptoms of depression. In contrast to this, a decreased sensitivity to experimental pain has been described in major depression. The physiological basis of this phenomenon is yet elusive. We investigated 30 patients suffering from a major depressive disorder and matched controls. Pain testing (threshold and tolerance) was performed on both sides of the body and included assessment of thermal, electrical and ischemic pain. While confirming hypoalgesia to heat and electrical pain in comparison to controls, we found hyperalgesia to ischemic muscle pain. Furthermore, thermal pain tolerance and electrical pain tolerance were significantly increased on the right hand side confirming previous results of a lateralized perception of pain in depression. Our main finding suggests that painful stimuli are processed differentially depending on the localization of pain induction in depression. This knowledge may enable us to understand and ultimately treat pain complaints more appropriately in depressed patients.
Assuntos
Transtorno Depressivo Maior/complicações , Medição da Dor/psicologia , Limiar da Dor/psicologia , Dor/psicologia , Adulto , Análise de Variância , Estudos de Casos e Controles , Estimulação Elétrica/efeitos adversos , Feminino , Lateralidade Funcional , Temperatura Alta/efeitos adversos , Humanos , Isquemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor/métodos , Limiar da Dor/fisiologiaRESUMO
OBJECTIVE: The aim of this study was to determine differing reactions of the left and right eyes with regard to pupillary light reflex (PLR) parameters. METHODS: All together 90 healthy subjects were included. In the first test series, 34 subjects were investigated on both eyes (left eye was tested first, three tests per day and one reliability test). In the second test series, 32 subjects were studied while changing the beginning side. In the last test series, 29 subjects were investigated 12 times each within 1h (beginning side changed, without spoken advice). Infrared pupillometry was used to study pupil diameter, latency time, relative amplitude, contraction/dilation velocity, and pupil redilation time. RESULTS: The study demonstrated significant differences of PLR parameters between both eyes. In contrast to the pupil diameter of the left eye the parasympathetically-dominated right eye was not influenced by vocal instructions or by changing the beginning side. CONCLUSIONS: PLR parameters might indicate functional lateralization of autonomic function in the central nervous system. High sensitivity of the procedure (arousal due to spoken advice, time of day) is advantageous for various psychophysiological investigations. SIGNIFICANCE: Differences between both eyes might point towards cortical lateralization of central autonomic function.