Additionally we believe it would have

Additionally, we believe it would have been valuable to investigate the presence of disturbed conditioned pain modulation (CPM) or inefficient descending pain inhibition in the chronic WAD group compared to controls. Subsequently, the efficacy of CPM could have been correlated with the rCBF of regions critically involved in descending pain inhibition such as the PAG (). Knowledge on these relations is important to further unravel the mechanisms of persistent pain. Alterations in epothilone perfusion in patients with chronic WAD compared to healthy controls using PET imaging have only been demonstrated by two other studies (). These studies included, in accordance to the present study, rather small sample sizes (n=18 and n=39). analyzed rCBF using O PET and found alterations in the parahippocampal and posterior cingulate gyrus, and thalamus in the chronic WAD group, which is according to the results of Vállez García et al. Furthermore, they observed alterations in regions which were not detected by Vállez García et al. (). Otte et al. used FDG (F) PET and only demonstrated hypometabolism in parieto-occipital regions in chronic WAD patients (). However, Otte et al. did not examine regional hyperperfusion. Interestingly, showed in a subanalysis also hypoperfusion in the posterior parietal occipital region. The latter result indicates that the previously reported alterations in this region have been underestimated and that maybe the brain is trying to compensate for this hypoperfusion by hyperperfusion in adjacent areas (). : The study by advances our understanding of chronic WAD and provides researchers and clinicians with innovative insights into the role of the brain in chronic WAD, however, only focused on alterations in rCBF. Because of the cross-sectional nature of the study, no conclusions can be drawn about the causal relationship between chronic pain and rCBF alterations. Consequently, there remain various critical questions that the field has yet to address regarding chronic pain in chronic WAD. What is the causal relationship between brain imaging results and the development and maintenance of persistent pain? Who is vulnerable to developing chronic pain and what underlies this vulnerability? To which structural and functional extent is the brain altered, measured with sophisticated MRI techniques, and what is the relation between brain alterations, and various clinical measures? Besides the chicken and the egg discussion, it will be a challenge for researchers to explore the effectiveness of different therapy strategies for chronic WAD patients by analyzing the effects of specific interventions on brain alterations as well as on clinical measures by using a longitudinal design. : The paper of provides innovative insights and confirmation of previously determined findings on the presence of rCBF alterations in brain regions involved in affective, motivational and cognitive processing of pain, and in regions part of the (cortico)limbic system in female patients with chronic WAD compared to healthy pain-free women. Furthermore, clinical important relations between rCBF alterations, and pain intensity, pain perception, pain-related disability, anxiety and depression were revealed. These results should impart to both scientists and clinicians, the knowledge that brain alterations possibly play a role in the persistent complaints of patients with chronic WAD. However, further research is absolutely warranted to unravel the specific role of the brain with the ultimate endeavour to improve pain treatment and to decrease suffering from pain. Disclosures
Introduction Hepatitis E virus (HEV) infection is being increasingly recognized in medical research as HEV infection has reached industrialized countries. Although HEV was discovered in 1983 (Balayan et al., 1983) and subsequent experimental analyses were initiated since 1990/1991 on HEV isolates (Reyes et al., 1990), there exists a considerable lack of understanding and knowledge of transmission routes, life-cycle, pathogenesis, genome variability and viral evolution.