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- Karshikoff, B., et al.
(författare)
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LPS increases pain sensitivity by decreased pain inhibition and increased insular activation
- 2015
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 49, s. e1-e1
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Tidskriftsartikel (refereegranskat)abstract
- We have shown that women are more prone to developing LPS-induced pain sensitivity than men, and that the descending endogenous pain inhibition is disrupted in women during experimental systemic inflammation. The aim of the present study was to investigate some of the central neural mechanisms underlying our previous findings. 51 participants (29 women) were injected with 0.6 ng/kg LPS or saline and went through a thumb-pressure pain fMRI paradigm 2 h after injection. As hypothesized, the subjects injected with LPS had decreased activity in the ventromedial prefrontal cortex and rostral anterior cingulate cortex (rACC), areas involved in descending pain inhibition. In addition, the LPS group had higher activity in the anterior insula, an area involved in medial/affective pain processing and interoception. These effects were not sex dependent. However, the male participants had overall stronger descending pain inhibition, reflected as a stronger rACC activity compared to women. It is possible that the more robust activation of descending pain inhibition rendered the men more resistant to the immune provocation, which may explain previously seen sex differences in LPS-induced pain sensitivity. Our findings give an indication to how the pain matrix is affected during a sickness response. The results strengthen the proposed link between systemic inflammation and weakened pain regulation in chronic pain disorders, and offers a possible mechanism underlying the female predominance in chronic pain disorders.
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- Gordon, AR, et al.
(författare)
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The scent of disease
- 2015
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Ingår i: CHEMICAL SENSES. - 0379-864X. ; 40:3, s. 254-254
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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- Karshikoff, Bianka, et al.
(författare)
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Why sickness hurts : A central mechanism for pain induced by peripheral inflammation
- 2016
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 57, s. 38-46
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Tidskriftsartikel (refereegranskat)abstract
- Low-grade systemic inflammation has been implicated in chronic pain, as well as in comorbid diseases like depression and fatigue. We have previously shown that women's pain perception and regulation is more affected by systemic inflammation than that of men. Here we investigated the neural substrates underlying these effects using an fMRI paradigm previously employed in a clinical population. Fifty-one participants (29 women) were injected with 0.6ng/kg lipopolysaccharide (LPS) or saline to induce a peripheral inflammatory response. The subjects were then tested with a pressure pain fMRI paradigm designed to capture descending pain inhibitory activity 2h after injection, and blood was sampled for cytokine analysis. The subjects injected with LPS became more pain sensitive compared to the placebo group, and the heightened pain sensitivity was paralleled by decreased activity in the ventrolateral prefrontal cortex and the rostral anterior cingulate cortex (rACC) compared to placebo; areas involved in descending pain regulation. The LPS group also had higher activity in the anterior insular cortex, an area underpinning affective and interoceptive pain processing. Women displayed overall less pain-evoked rACC activity compared to men, which may have rendered women less resilient to immune provocation, possibly explaining sex differences in LPS-induced pain sensitivity. Our findings elucidate the pain-related brain circuits affected by experimental peripheral inflammation, strengthening the theoretical link between systemic inflammation and weakened pain regulation in chronic pain disorders. The results further suggest a possible mechanism underlying the female predominance in many chronic pain disorders.
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6. |
- Koeck, P. J. B., et al.
(författare)
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Limitations of the linear and the projection approximations in three-dimensional transmission electron microscopy of fully hydrated proteins
- 2015
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Ingår i: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 259:3, s. 197-209
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Tidskriftsartikel (refereegranskat)abstract
- We establish expressions for the linear and quadratic terms in the series expansion of the phase and the phase and amplitude object description of imaging thin specimens by transmission electron microscopy. Based on these expressions we simulate the corresponding contributions to images of unstained protein complexes of varying thickness and arrive at an estimate for how much each term contributes to the contrast of the image. From this we can estimate a maximum specimen thickness for which the weak phase and the weak amplitude and phase object approximation (and therefore linear imaging) is still reasonably accurate. When discussing thick specimens it is also necessary to consider limitations due to describing the image as a filtered projection of the specimen, since the different layers of the specimen are not imaged with the same defocus value. We therefore compared simulations based on the projection approximation with the more accurate multislice model of image formation. However, we find that the errors due to nonlinear image contributions are greater than those due to the defocus gradient for the defocus values chosen for the simulations. Finally, we study how the discussed nonlinear image contributions and the defocus gradient affect the quality of three-dimensional reconstructions. We find that three-dimensional reconstructions reach high resolution when at the same time exhibiting localized systematic structural errors. Non-Technical Abstract Cryo transmission electron microscopy and three-dimensional reconstruction can be used to determine a three-dimensional model of a protein molecule. In the mathematical methods used for three-dimensional reconstruction assumptions are made about a linear relationship between the images recorded in the electron microscope and the objects being imaged. In this paper we investigate with computer simulations at what specimen thickness these assumptions start breaking down and what sort of errors can be expected in the three-dimensional reconstructions when the assumptions are not valid anymore.
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7. |
- Sundelin, Tina, et al.
(författare)
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Sick man walking : Perception of health status from body motion
- 2015
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Ingår i: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 48, s. 53-56
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Tidskriftsartikel (refereegranskat)abstract
- An ability to detect subtle signs of sickness in others would be highly beneficial, as it would allow for behaviors that help us avoid contagious pathogens. Recent findings suggest that both animals and humans are able to detect distinctive odor signals of individuals with activated innate immune responses. This study tested whether an innate immune response affects a person's walking speed and whether other people perceive that person as less healthy. 43 subjects watched films of persons who were experiencing experimental immune activation, and rated the walking individuals in the films with respect to health, tiredness, and sadness. Furthermore, the walking speed in the films was analyzed. After LPS injections, participants walked more slowly and were perceived as less healthy and more tired as compared to when injected with placebo. There was also a trend for the subjects to look sadder after LPS injection than after placebo. Furthermore, there were strong associations between walking speed and the appearance of health, tiredness, and sadness. These findings support the notion that walking speed is affected by an activated immune response, and that humans may be able to detect very early signs of sickness in others by merely observing their gait. This ability is likely to aid both a "behavioral immune system", by providing more opportunities for adaptive behaviors such as avoidance, and the anticipatory priming of biochemical immune responses.
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