Schizophrenia is increasingly recognized as a neurodevelopmental disease with an additional degenerative component, comprising cognitive decline and loss of cortical gray matter. We hypothesized that a neuroprotective/neurotrophic add-on strategy, recombinant human erythropoietin (rhEPO) in addition to stable antipsychotic medication, may be able to improve cognitive function even in chronic schizophrenic patients. Therefore, we designed a doubleblind, placebo-controlled, randomized, multicenter, proof-of-principle (phase II) study. This study had a total duration of 2 years and an individual duration of 12 weeks with an additional safety visit at 16 weeks. Chronic schizophrenic men (N = 39) with defined cognitive deficit (X1 s.d. below normal in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)), stable medication and disease state, were treated for 3 months with a weekly short (15 min) intravenous infusion of 40 000 IU rhEPO (N = 20) or placebo (N = 19). Main outcome measure was schizophrenia-relevant cognitive function at week 12. The neuropsychological test set (RBANS subtests delayed memory, language-semantic fluency, attention and Wisconsin Card Sorting Test (WCST-64) -perseverative errors) was applied over 2 days at baseline, 2 weeks, 4 weeks and 12 weeks of study participation. Both placebo and rhEPO patients improved in all evaluated categories. Patients receiving rhEPO showed a significant improvement over placebo patients in schizophrenia-related cognitive performance (RBANS subtests, WCST-64), but no effects on psychopathology or social functioning. Also, a significant decline in serum levels of S100B, a glial damage marker, occurred upon rhEPO. The fact that rhEPO is the first compound to exert a selective and lasting beneficial effect on cognition should encourage new treatment strategies for schizophrenia.

The present findings suggest that sleep deprivation produces hyperalgesic changes that cannot be explained by nonspecific alterations in somatosensory functions.

Nonlinear ionic interactions at the nerve cell membrane can account for oscillating membrane potentials and the generation of periodic neuronal impulse activity. In combination with noise, external modulation of the endogenous oscillations allows for continuous transitions between a variety of impulse patterns. Such "noisy oscillators" afford, thereby, an important mechanism of neuronal encoding as is demonstrated here with experimental data from peripheral cold receptors and corresponding computer simulations.

The aim of the present study was to characterize the EEG response pattern specific for tonic pain which is an experimental pain model resembling clinical pain more closely than phasic pain. Tonic experimental pain was produced by a series of heat pulses 1 degree C above pain threshold over 10 min. A series of heat pulses 0.3 degree C below pain threshold and a constant temperature of 37 degrees C served as non-painful heat control and as baseline condition, respectively. The level of attention was experimentally manipulated by instruction and by a distraction task. Twenty male, pain-free subjects had to rate the sensation intensity and sensation unpleasantness during thermal stimulation. Furthermore, a German version of the McGill Pain Questionnaire was to be filled out after tonic painful heat stimulation. The EEG was recorded via 10 leads according to 10/20 convention. Power density was calculated for the usual frequency bands. The ratings showed that tonic painful heat was experienced clearly distinct from tonic non-painful heat. An EEG response pattern emerged characterized by a rather generalized increased delta(2) activity, a left-biased fronto-temporally diminished theta activity, a fronto-temporal decrease in the alpha(1) activity and a left-sided temporal increase in the beta(1) activity. This observation agrees well with the findings of others. However, there was no evidence in our data that these EEG changes are specific to tonic heat pain as opposed to changes observed during tonic non-painful heat stimulation. Accordingly, the repeatedly reported EEG patterns are also likely to be produced by other forms of strong somatosensory stimuli and to be not specific for pain.

The German version of the FFI is a reliable and valid questionnaire for the self-assessment of pain and disability in German-speaking patients with foot complaints.