Highlights • Pain is modulated by different contexts, ranging from positive to negative. • Positive contexts decrease pain through opioid and cannabinoid systems. • Negative contexts increase pain ...through cholecystokinin and prostaglandins. • Pain can be even perceived as a rewarding experience in the appropriate context. • Eliminating a positive context reduces the response to a painkiller.
Abstract
Bipolar disorder (BD) has been consistently associated with alterations in the immune system. Evidence suggests a condition of systemic low-grade inflammation due to decreased adaptive, ...increased innate immunity, with higher levels of circulating cytokines, higher macrophage/monocyte inflammatory activation patterns, and higher neutrophils to lymphocyte counts; and with a dynamic pattern of premature immunosenescence and partial T cell defect starting early in adolescence, involving a reduction of naïve T cells and an expansion of memory and senescent T cells. Quantitative analysis of circulating inflammatory markers suggested persistent low-grade inflammation.
A growing literature suggests that the immune system plays a core role in maintaining brain homeostasis, with both adaptive and innate immune support, ensured by cell trafficking across the blood brain barrier, being essential for brain maintenance and repair in healthy conditions, and disrupted in brain disorders including BD. Measured in peripheral blood, these markers of altered immuno-inflammatory setpoints parallel activation of microglia and disruption of white matter (WM) integrity in the brain.
Studies in the field are in its infancy, but findings by our group showed that: circulating Th17 cells correlated with higher FA, while regulatory FOXP3
+
cells correlated with higher RD and MD, and with lower fMRI neural responses in the right dorsolateral prefrontal cortex; higher circulating cytokine-producing NK cells were fostered by ongoing lithium treatment and directly correlated with better FA, and inversely with RD and MD, also partially mediating the known benefits from lithium on WM; and activation status and expression of killer proteins by cytotoxic CD8
+
T cells negatively associated with WM microstructure, thus suggesting that CD8
+
T cells can leave the blood stream to migrate into the brain and induce an immune-related WM damage in BD.
Implications of these findings for neuroprogression, clinical outcomes, and new treatment strategies of the disorder will be discussed.
Disclosure of Interest
None Declared
Macrophage activation syndrome (MAS) refers to acute overwhelming inflammation caused by a 'cytokine storm'. Although increasingly recognized as a life-threatening complication of various rheumatic ...diseases, clinically, MAS is strikingly similar to primary and secondary forms of haemophagocytic lymphohistiocytosis (HLH). Not surprisingly, many rheumatologists prefer the term secondary HLH rather than MAS to describe this condition, and efforts to change the nomenclature are in progress. The pathophysiology of MAS remains elusive, but observations in animal models, as well as data on the effects of new anticytokine therapies on rates and clinical presentations of MAS in patients with systemic juvenile idiopathic arthritis (sJIA), provide clues to the understanding of this perplexing clinical phenomenon. In this Review, we explore the latest available evidence and discuss potential diagnostic challenges in the era of increasing use of biologic therapies.
The nocebo effect consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Here we show that nocebo suggestions, in which expectation of pain ...increase is induced, are capable of producing both hyperalgesic and allodynic responses. By extending previous findings on the placebo effect, we investigated the role of learning in the nocebo effect by means of a conditioning procedure. To do this, verbal suggestions of pain increase were given to healthy volunteers before administration of either tactile or low-intensity painful electrical stimuli. This nocebo procedure was also carried out after a pre-conditioning session in which two different conditioned visual stimuli were associated to either pain or no-pain. Pain perception was assessed by means of a Numerical Rating Scale raging from 0
=
tactile to 10
=
maximum imaginable pain. We found that verbal suggestions alone, without prior conditioning, turned tactile stimuli into pain as well as low-intensity painful stimuli into high-intensity pain. A conditioning procedure produced similar effects, without significant differences. Therefore, in contrast to placebo analgesia, whereby a conditioning procedure elicits larger effects compared to verbal suggestions alone, learning seems to be less important in nocebo hyperalgesia. Overall, these findings indicate that, by defining hyperalgesia as an increase in pain sensitivity and allodynia as the perception of pain in response to innocuous stimulation, nocebos can indeed produce both hyperalgesic and allodynic effects. These results also suggest that learning is not important in nocebo hyperalgesia compared to placebo analgesia.
In this study, mono-, bi-, and tri-metallic engineered nanoparticles (ENPs) are first analysed using an ICP-ToF-MS in single particle mode. The method is also used to characterize natural NPs (NNPs) ...(
i.e.
oxide and clay minerals). We provide here the elemental composition and mass distribution of these different NPs. For the first-time using spICP-ToF-MS, the presence of Ti- and Si-NPs as well as that of a second population with a distinct Si-Al ratio is highlighted in kaolinite. Finally, for mixtures of the different original NPs, an automated post-processing approach based on hierarchical agglomerative clustering (HAC) is applied. The elemental signature of the different clusters is in agreement with the results of previous characterizations. This illustrates the applicability of coupling spICP-ToF-MS with HAC to determine elemental fingerprints of NPs and to differentiate one from the other when mixed. The described methodology could be a starting point to simplify the analysis and make reliable interpretations of unknown NP populations and thereby more accurately understand NP populations in natural systems. However, as illustrated, thorough evaluation of the data must be performed in order to avoid misclassification of the NPs in future studies.
Characterization and identification of multielement nanoparticles thanks to the use of a spICP-ToF-MS coupled to hierarchical agglomerative clustering (HAC).
The anti–interleukin-1 antibody canakinumab was effective at controlling and preventing recurrence of flares in autoimmune inflammatory diseases: familial Mediterranean fever, mevalonate kinase ...deficiency, and the TNF receptor–associated periodic syndrome.
Considerable progress has been made in our understanding of the neurobiological mechanisms of the placebo effect, and most of our knowledge originates from the field of pain and analgesia. Today, the ...placebo effect represents a promising model that could allow us to shed new light on mind-body interactions. The mental events induced by placebo administration can activate mechanisms that are similar to those activated by drugs, which indicates a similarity between psychosocial and pharmacodynamic effects. These new neurobiological advances are already changing our conception of how clinical trials and medical practice must be viewed and conducted.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Recent reports suggest that significant fractionation of stable metal isotopes occurs during biogeochemical cycling and that the uptake into higher plants is an important process. To test isotopic ...fractionation of copper (Cu) and zinc (Zn) during plant uptake and constrain its controls, we grew lettuce, tomato, rice and durum wheat under controlled conditions in nutrient solutions with variable metal speciation and iron (Fe) supply. The results show that the fractionation patterns of these two micronutrients are decoupled during the transport from nutrient solution to root. In roots, we found an enrichment of the heavier isotopes for Zn, in agreement with previous studies, but an enrichment of isotopically light Cu, suggesting a reduction of Cu(II) possibly at the surfaces of the root cell plasma membranes. This observation holds for both graminaceous and nongraminaceaous species and confirms that reduction is a predominant and ubiquitous mechanism for the acquisition of Cu into plants similar to the mechanism for the acquisition of iron (Fe) by the strategy I plant species. We propose two preliminary models of isotope fractionation processes of Cu and Zn in plants with different uptake strategies.
Abstract The nocebo effect is a phenomenon that is opposite to the placebo effect, whereby expectation of a negative outcome may lead to the worsening of a symptom. Thus far, its study has been ...limited by ethical constraints, particularly in patients, as a nocebo procedure is per se stressful and anxiogenic. It basically consists in delivering verbal suggestions of negative outcomes so that the subject expects clinical worsening. Although some natural nocebo situations do exist, such as the impact of negative diagnoses upon the patient and the patient’s distrust in a therapy, the neurobiological mechanisms have been understood in the experimental setting under strictly controlled conditions. As for the placebo counterpart, the study of pain has been fruitful in recent years to understand both the neuroanatomical and the neurochemical bases of the nocebo effect. Recent experimental evidence indicates that negative verbal suggestions induce anticipatory anxiety about the impending pain increase, and this verbally-induced anxiety triggers the activation of cholecystokinin (CCK) which, in turn, facilitates pain transmission. CCK-antagonists have been found to block this anxiety-induced hyperalgesia, thus opening up the possibility of new therapeutic strategies whenever pain has an important anxiety component. Other conditions, such as Parkinson’s disease, although less studied, have been found to be affected by nocebo suggestions as well. All these findings underscore the important role of cognition in the therapeutic outcome, and suggest that nocebo and nocebo-related effects might represent a point of vulnerability both in the course of a disease and in the response to a therapy.
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