Current trends in neuropathic pain treatments with special reference to fibromyalgia

Neuropathic pain and fibromyalgia are prevalent diseases which have major consequences on healthcare resources and the individual. From the clinical point of view neuropathic pains represent a heterogeneous group of aetiologically different diseases ranging from cancer to diabetes. Patients with fibromyalgia also display clinical features common in neuropathic pain suggesting that there might be some overlap. The mechanisms responsible for symptoms and signs in both diseases are still unknown. Recently, there have been numerous reports of various pharmacological treatments of neuropathic pain and fibromyalgia with often disappointing results. Most of the studies were of short duration, had high attrition rates, and displayed other methodological problems. Some compounds had high rates of adverse effects which makes it often difficult for the patients to tolerate the treatment, especially in the long-term. At present, the best options for medication treatment are tricyclic antidepressants in lower dosage than usual in psychiatric disorders and a wide range of anticonvulsants. Opioids are sometimes recommended but have been found to have minor efficacy. Recently, there have been more controlled trials, which are reported here if they had been published between 2002 and 2004. Various compounds have been tested in different studies. Treatment of fibromyalgia, which has many features in common with depressive symptoms, became the focus of interest. New promising studies with dual serotonin-norepinephrine reuptake inhibitors (duloxetine and milnacipram) and a newer antiepileptic drug (pregabalin) are in progress. Future research will have to apply new approaches (e.g., using a mechanism-based classification of neuropathic pain and carrying out studies in populations with the same symptom but not necessarily the same disease) in order to find effective treatments for these common and often debilitating diseases.     

The paradox of quetiapine in obsessive-compulsive disorder

Schizophrenia and obsessive-compulsive disorder (OCD) have historical, clinical, and epidemiological links. The clinical use of atypical neuroleptics (ie, dual serotonin-dopamine antagonists) to treat both conditions sheds a new light on them. We report the first two cases of obsessive-compulsive symptoms (OCS) induced by quetiapine in schizophrenia patients. A case of successful augmentation by quetiapine in refractory OCD is also presented. A review of the literature on OCS induced by atypical neuroleptics follows. This paradoxically induced OCD symptomology in schizophrenia patients administered atypical neuroleptics is discussed from new pathophysiological and clinical perspectives. The discussion emphasizes the prognostic implications of OCS in schizophrenia and available therapies for this comorbidity.     

APP23 mice as a model of Alzheimer's disease: an example of a transgenic approach to modeling a CNS disorder

Animal models are considered essential in research ensuing elucidation of human disease processes and subsequently, testing of potential therapeutic strategies. This is especially true for neurodegenerative disorders, in which the first steps in pathogenesis are often not accessible in human patients. Alzheimer's disease is vastly becoming a major medical and socioeconomic problem in our aging society. Valid animal models for this uniquely human condition should exhibit histopathological, biochemical, cognitive, and behavioral alterations observed in Alzheimer's disease patients. Major progress has been made since the understanding of the genetic basis of Alzheimer's disease and the development and improvement of transgenic mouse models. All present Alzheimer's disease models developed are partial but nevertheless essential in further unraveling the nature and spatial and temporal development of the complex molecular pathology underlying this condition. One of the more recent transgenic attempts to model Alzheimer's disease is the APP23 transgenic mouse. This article describes the development and assessment of this human amyloid precursor protein overexpression model. We summarize histopathological and biochemical, cognitive and behavioral observations made in heterozygous APP23 mice, thereby emphasizing the model's contribution to clarification of neurodegenerative disease mechanisms. In addition, the first therapeutic interventions in the APP23 model are included.     

Writing brains: tracing the psyche with the graphical method

At the end of the 19th century, the graphic method kindled attempts to use it for investigating psychic processes. In Germany, Hans Berger took up this line of research, later to become the pioneer of electroencephalography (EEG). This trajectory of Berger's work is analyzed as an "enabling constraint" guiding him toward the EEG at a time when nobody else was pursuing this line of research and also causing serious methodological problems. In the epistemological perspective of this analysis, many of his problems extend beyond the local context of his work and point toward ambiguities surrounding the project to trace the psyche with the graphic method. From the mid-1930s, the EEG inspired ongoing attempts to decipher the specific meanings of these recordings, and large ensembles of machinery were mobilized, molding concepts of the psyche according to the results and the specifications of the graphic method.     

Simulation of the filtering role of habituation to stimuli

In the context of a medium-term study designed to integrate the simulation of different types and processes of learning-such as classical, operant, and some cognitive types--one must start with other more elementary ones that are facilitators of the more complex types and processes. Of special interest is habituation, owing to the filtering out of irrelevant stimuli, which means that the simulated agent does not have to respond to them. This paper presents two difference functions constructed to computationally simulate the characteristics that define habituation. The behavior of these functions is described, as are differences arising from stimulus intensity and interstimulus intervals. Results are compared with existing empirical data.     

One-year-olds comprehend the communicative intentions behind gestures in a hiding game

This study explored infants' ability to infer communicative intent as expressed in non-linguistic gestures. Sixty children aged 14, 18 and 24 months participated. In the context of a hiding game, an adult indicated for the child the location of a hidden toy by giving a communicative cue: either pointing or ostensive gazing toward the container containing the toy. To succeed in this task children had to do more than just follow the point or gaze to the target container. They also had to infer that the adult's behaviour was relevant to the situation at hand - she wanted to inform them that the toy was inside the container toward which she gestured. Children at all three ages successfully used both types of cues. We conclude that infants as young as 14 months of age can, in some situations, interpret an adult behaviour as a relevant communicative act done for them.     

New approaches to demystifying insight

After a person has become stuck on a problem, they sometimes achieve a clear and sudden solution through insight--the so-called Aha! experience. Because of its distinctive experience, the origins and characteristics of insight have received considerable attention historically in psychological research. However, despite considerable progress in characterizing insight, the underlying mechanisms remain mysterious. We argue that research on insight could be greatly advanced by supplementing traditional insight research, which depends on a few complex problems, with paradigms common in other domains of cognitive science. We describe a large set of mini-insight problems to which multiple methods can be applied, together with subjective reports to identify insight problem-solving. Behavioral priming and neuroimaging methods are providing evidence about what, where, and how neural activity occurs during insight. Such evidence constrains theories of component processes, and will help to demystify insight.     

Eye movements in natural behavior

The classic experiments of Yarbus over 50 years ago revealed that saccadic eye movements reflect cognitive processes. But it is only recently that three separate advances have greatly expanded our understanding of the intricate role of eye movements in cognitive function. The first is the demonstration of the pervasive role of the task in guiding where and when to fixate. The second has been the recognition of the role of internal reward in guiding eye and body movements, revealed especially in neurophysiological studies. The third important advance has been the theoretical developments in the fields of reinforcement learning and graphic simulation. All of these advances are proving crucial for understanding how behavioral programs control the selection of visual information.