Plos One
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Fear conditioning is relevant for elucidating the pathophysiology of anxiety, but may also be useful in the context of chronic pain syndromes which often overlap with anxiety. Thus far, no fear conditioning studies have employed aversive visceral stimuli from the lower gastrointestinal tract. Therefore, we implemented a fear conditioning paradigm to analyze the conditioned response to rectal pain stimuli using fMRI during associative learning, extinction and reinstatement. ⋯ During extinction, conditioned responses quickly disappear, and learning of new predictive cue properties is paralleled by prefrontal activation. A tendency for parahippocampal activation during reinstatement could indicate a reactivation of the old memory trace. Together, these findings contribute to our understanding of aversive visceral learning and memory processes relevant to the pathophysiology of chronic abdominal pain.
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Post-cardiac arrest myocardial dysfunction is a major cause of mortality in patients receiving successful cardiopulmonary resuscitation (CPR). Mild therapeutic hypothermia (MTH) is the recommended treatment after resuscitation from cardiac arrest (CA) and is known to exert neuroprotective effects and improve short-term survival. Yet its cytoprotective mechanisms are not fully understood. ⋯ Our results indicated that the endothelin system was not upregulated at 30, 60 and 180 min after ROSC in untreated postcardiac arrest syndrome. Post-resuscitative 3 hour-long treatments either with MTH or S-PBN stimulated ET-1, ECE-1, ETAR and ETBR as well as neuronal NOS and endothelial NOS in left ventricular cardiomyocytes. Our data suggests that the endothelin and nitric oxide pathways are activated by MTH in the heart.
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Chronic pain is the most prominent and disabling symptom of osteoarthritis (OA). Clinical data suggest that subchondral bone lesions contribute to the occurrence of joint pain. The present study investigated the effect of the inhibition of subchondral bone lesions on joint pain. ⋯ The inhibition of subchondral bone lesions alleviated joint pain. Subchondral bone lesions should be a key target in the management of osteoarthritic joint pain.
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It is becoming increasingly evident that genetic variants contribute to the development of opioid addiction. An elucidation of these genetic factors is crucial for a better understanding of this chronic disease and may help to develop novel therapeutic strategies. In recent years, several candidate genes were implicated in opioid dependence. ⋯ The present study provides further support for a contribution of GAL and OPRD1 variants to the development of opioid addiction. Furthermore, our results indicate a potential contribution of OPRM1 and ABCB1 SNPs to the development of this chronic relapsing disease. Therefore it seems important that these genes are addressed in further addiction related studies.
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MicroRNAs (miRNAs) have been shown to be involved in different aspects of cancer biology including tumor angiogenesis. In this study, we identified that two miRNAs, miR-199a and miR-125b were downregulated in ovarian cancer tissues and cell lines. Overexpression of miR-199a and miR-125b inhibited tumor-induced angiogenesis associated with the decrease of HIF-1α and VEGF expression in ovarian cancer cells. ⋯ We further showed that direct targets of miR-199a and miR-125b HER2 and HER3 were functionally relevant. Forced expression of HER2 and HER3 rescued miR-199a- and miR-125b-inhibiting angiogenesis responses and Akt/p70S6K1/HIF-1α pathway. This study provides a rationale for new therapeutic approach to suppress tumor angiogenesis using miR-199a, miR-125b, or their mimics for ovarian cancer treatment in the future.