Principle components analysis of pain thresholds to thermal, electrical, and mechanical stimuli suggests a predominant common source of variance

We addressed the question whether pain thresholds to different stimuli measure independent aspects of pain or one common phenomenon. In the first case, different stimuli are required to completely characterize a subject’s pain sensitivity. In the second case, different stimuli are redundant and can be used to calculate composite scores across pain modalities. We measured pain thresholds to several stimuli (heat, heat/capsaicin, cold, cold/menthol, blunt pressure, 5-Hz sine-wave electric current (0–20 mA), punctate pressure (von Frey hairs), and von Frey hairs plus capsaicin application) in 45 healthy men and 32 healthy women (aged 20–44 years). We observed that pain thresholds were significantly correlated with each other. Principal component analysis indicated that their variance was attributable more to the difference in subjects (variance estimate: 0.393) than to the difference in pain stimuli within a subject (variance estimate: −0.008). Among three principal components of the intercorrelation matrix with eigenvalues >1, the first, explaining 48% of the total variance, carried high loadings from all stimuli indicating that they shared a common source of half of their variance. Only minor variance components, each explaining <14% of the total variance, indicated a distinction of pain stimuli. There, a pattern of similarities and dissimilarities emerged agreeing with known distinct mechanisms of nociceptive responses to different stimuli. We conclude that characterizing a person as being generally stoical or complaining to any painful stimulus appears to be justified at least at pain threshold level.     

T lymphocytes in implant-associated posttraumatic osteomyelitis: Identification of cytotoxic T effector cells at the site of infection

In implant-associated posttraumatic osteomyelitis, a massive infiltration of leukocytes into the infected site is seen. As described previously, the most infiltrated cells were highly activated polymorphonuclear neutrophils. In addition, a considerable T-cell infiltrate was noted. Whereas our previous work was mainly concerned with the phenotypical and functional characterization of the polymorphonuclear neutrophils, we now analyzed T lymphocytes of 32 patients with implant-associated posttraumatic osteomyelitis. We found evidence for an expansion of CD8 T cells in the peripheral blood of the patients and for an infiltration of these cells into the infected site. Further analysis of the surface-receptor pattern by three-color cytofluorometry revealed that the majority of these cells belonged to the cytotoxic-effector phenotype. Of note is that cytotoxic T cells are generally associated with virus infection. Thus, the detection of those cells in patients with bacterial infection was rather unexpected and points to a novel, not yet appreciated, role of CD8 T cells also in the defense of bacterial infections.     

Targeted deletion of Vglut2 expression in the embryonal telencephalon promotes an anxiolytic phenotype of the adult mouse

Background

Anxiety is a natural emotion experienced by all individuals. However, when anxiety becomes excessive, it contributes to the substantial group of anxiety disorders that affect one in three people and thus are among the most common psychiatric disorders. Anxiolysis, the reduction of anxiety, is mediated via several large groups of therapeutical compounds, but the relief is often only temporary, and increased knowledge of the neurobiology underlying anxiety is needed in order to improve future therapies.

Aim

We previously demonstrated that mice lacking forebrain expression of the Vesicular glutamate transporter 2 (Vglut2) from adolescence showed a strong anxiolytic behaviour as adults. In the current study, we wished to analyse if removal of Vglut2 expression already from mid-gestation of the mouse embryo would give rise to similar anxiolysis in the adult mouse.

Methods

We produced transgenic mice lacking Vglut2 from mid-gestation and analysed their affective behaviour, including anxiety, when they had reached adulthood.

Results

The transgenic mice lacking Vglut2 expression from mid-gestation showed certain signs of anxiolytic behaviour, but this phenotype was not as prominent as when Vglut2 was removed during adolescence.

Conclusion

Our results suggest that both embryonal and adolescent forebrain expression of Vglut2 normally contributes to balancing the level of anxiety. As the neurobiological basis for anxiety is similar across species, our results in mice may help improve the current understanding of the neurocircuitry of anxiety, and hence anxiolysis, also in humans.