| 1. |
- Andreasson, Anna N., et al.
(author)
-
Development and preliminary validation of the Sickness Questionnaire (SicknessQ)
- 2013
-
In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 32
-
Journal article (peer-reviewed)abstract
- The lack of questionnaires to measure subjective feelings of being sick made us develope the Sickness Questionnaire (SicknessQ) for assessment of sickness behavior in people. The objective of the present investigation was to test its internal consistency, criteria validity, and sensitivity to capture the sickness response in an experimental setting. An initial pool of items was developed based on previous research. The statistical properties of SicknessQ was assessed in 172 men and women primary care patients with acute complaints and involved three steps: (1) principal component analyses to reduce the number of items and to identify latent factor structures, (2) tests of internal consistencies of subscales, and (3) hierarchical regression analyses to test criteria validity of the subscales. Subsequently, sensitivity to change was tested in a placebo controlled experiment in which 31 blinded healthy men and women were injected with endotoxin (LPS) to provoke sickness behavior. Principal components analysis suggested a 3-factor solution with a total of 11 items measuring fatigue (5 items), pain (4 items) and emotion (2 items). The total scale as well as each of the three separate factors were significantly changed 90 min after endotoxin injection as compared to baseline (p’s < .01). In all, the new 11-item SicknessQ is highly sensitive to a mild systemic inflammation. Further studies are planned to test its usefulness and prognostic value in clinical settings.
|
|
| 2. |
- Karshikoff, B., et al.
(author)
-
LPS increases pain sensitivity by decreased pain inhibition and increased insular activation
- 2015
-
In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 49, s. e1-e1
-
Journal article (peer-reviewed)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.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Gordon, AR, et al.
(author)
-
The scent of disease
- 2015
-
In: CHEMICAL SENSES. - 0379-864X. ; 40:3, s. 254-254
-
Conference paper (other academic/artistic)
|
|
| 7. |
- Karshikoff, B., et al.
(author)
-
Modality and sex differences in pain sensitivity during human endotoxemia
- 2014
-
In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 46, s. 35-43
-
Journal article (peer-reviewed)abstract
- Systemic inflammation can induce pain hypersensitivity in animal and human experimental models, and has been proposed to be central in clinical pain conditions. Women are overrepresented in many chronic pain conditions, but experimental studies on sex differences in pain regulation during systemic inflammation are still scarce. In two randomized and double blind placebo controlled experiments, we used low doses of lipopolysaccharide (LPS) as an experimental model of systemic inflammation. The first study employed 0.8ng/kg LPS in a within-subject design of 8 individuals (1 woman), and the second study 0.6ng/kg LPS in a between-subject design of 52 participants (29 women). We investigated the effect on (a) pressure, heat, and cold pain thresholds, (b) suprathreshold noxious heat and cold sensitivity, and (c) conditioned pain modulation (CPM), and differences between men and women. LPS induced significantly lower pressure pain thresholds as compared to placebo (mean change with the 0.8ng/kg dose being -64±30kPa P=.04; with the 0.6ng/kg dose -58±55kPa, P<.01, compared to before injection), whereas heat and cold pain thresholds remained unaffected (P's>.70). Suprathreshold noxious pain was not affected by LPS in men (P's⩾.15). However, LPS made women rated suprathreshold noxious heat stimuli as more painful (P=.01), and showed a tendency to rate noxious cold pain as more painful (P=.06) as compared to placebo. Furthermore, LPS impaired conditioned pain modulation, a measure of endogenous pain inhibition, but this effect was also restricted to women (P<.01, for men P=.27). Pain sensitivity correlated positively with plasma IL-6 and IL-8 levels. The results show that inflammation more strongly affects deep pain, rather than cutaneous pain, and suggest that women's pain perception and modulation is more sensitive to immune activation than men's.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Karshikoff, B, et al.
(author)
-
Relationship Between Blood Cytokine Levels, Psychological Comorbidity, and Widespreadness of Pain in Chronic Pelvic Pain
- 2021
-
In: Frontiers in psychiatry. - : Frontiers Media SA. - 1664-0640. ; 12, s. 651083-
-
Journal article (peer-reviewed)abstract
- Background: Low-grade inflammation has been implicated in the etiology of depression, long-term fatigue and chronic pain. TNFα and IL-6 are perhaps the most studied pro-inflammatory cytokines in the field of psychoneuroimmunology. The purpose of our study was to further investigate these relationships in patients with chronic pelvic pain specifically. Using plasma samples from a large, well-described cohort of patients with pelvic pain and healthy controls via the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network, we examined the relationship between TNFα and IL-6 and comorbid psychological symptoms. We also investigated the relationship between IL-8 and GM-CSF, and widespreadness of pain.Methods: We included baseline blood samples in the analyses, 261 patients (148 women) and 110 healthy controls (74 women). Fourteen pro- and anti-inflammatory or regulatory cytokines were analyzed in a Luminex® xMAP® high-sensitivity assay. We used regression models that accounted for known factors associated with the outcome variables to determine the relationship between cytokine levels and clinical measures.Results: There were no statistical differences in cytokine levels between patients and healthy controls when controlling for age. In patients, TNFα was significantly associated with levels of fatigue (p = 0.026), but not with pain intensity or depression. IL-6 was not significantly related to any of the outcome variables. Women with pelvic pain showed a negative relationship between IL-8 and widespreadness of pain, while men did not (p = 0.003). For both sexes, GM-CSF was positively related to widespreadness of pain (p = 0.039).Conclusion: Our results do not suggest low-grade systemic inflammation in chronic pelvic pain. Higher TNFα blood levels were related to higher fatigue ratings, while higher systemic GM-CSF levels predicted more widespread pain. Our study further suggests a potentially protective role of IL-8 with regard to with regard to the widepreadness of pain in the body, at least for women.
|
|
| 11. |
- Karshikoff, Bianka, et al.
(author)
-
Why sickness hurts : A central mechanism for pain induced by peripheral inflammation
- 2016
-
In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 57, s. 38-46
-
Journal article (peer-reviewed)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.
|
|
| 12. |
- Knapp, S, et al.
(author)
-
Thermal unfolding of the DNA-binding protein Sso7d from the hyperthermophile Sulfolobus solfataricus
- 1996
-
In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 264:5, s. 1132-1144
-
Journal article (peer-reviewed)abstract
- Thermal unfolding of the small hyperthermophilic DNA-binding protein Sso7d was studied by circular dichroism spectroscopy and differential scanning calorimetry. The unfolding transition can be described by a reversible two state process. Maximum stability was observed in the region between pH 4.5 and 7.0 where Sso7d unfolds with a melting temperature between 370.8 to 371.9 K and an unfolding enthalpy between 62.9 and 65.4 kcal/mol. The heat capacity differences between the native and the heat denatured states obtained by differential scanning calorimetry (620 cal/(mol K)) and circular dichroism spectroscopy (580 cal/(mol K)) resulted in comparable values. The thermodynamic reason for the high melting temperature of Sso7d is the shallow stability curve with a broad free energy maximum, corresponding to the relatively small heat capacity change which was obtained. The calculated stability curve shows that Sso7d has, despite of its high melting temperature, an only moderate intrinsic stability, which reaches its maximum (approximate to 7 kcal/mol) at 282 K. Sso7d is particularly poorly stabilized (approximate to 1 kcal/mol) at the maximum physiological growth temperature of Sulfolobus solfataricus. Sso7d has furthermore untypically low specific enthalpy (0.99 kcal/(mol residue)) and entropy (2.99 cal/(mol K)) values at convergence temperatures. No significant differences in thermal stability of the partially methylated Sso7d from Sulfolobus solfataricus and the cloned non-methylated form of the protein expressed in Escherichia coli were observed. (C) 1996 Academic Press Limited
|
|
| 13. |
- Koeck, P. J. B., et al.
(author)
-
Limitations of the linear and the projection approximations in three-dimensional transmission electron microscopy of fully hydrated proteins
- 2015
-
In: Journal of Microscopy. - : Wiley. - 0022-2720 .- 1365-2818. ; 259:3, s. 197-209
-
Journal article (peer-reviewed)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.
|
|
| 14. |
- Lidberg, Lisa, et al.
(author)
-
Self-rated health in response to experimental manipulations of inflammation is mediated by sickness behavior as assessed by the sickness questionnaire
- 2013
-
In: Brain, Behavior, and Immunity. - : Elsevier BV. - 0889-1591. ; 32:Supplement, s. e34-e34
-
Journal article (peer-reviewed)abstract
- Factors that influence subjective health ratings (e.g. pain, tiredness, lack of energy) resemble immune activated sickness behavior. Accordingly, previous research has shown a relation between inflammatory cytokines and poor self-rated health. However, neither the causality of the association, nor what mediates it, is clear. In this study we investigated if a transient immune activation would affect subjective health perception and, if so, if this effect is mediated by symptoms of sickness behavior. Using a between-subject design, 51 healthy subjects were injected with either endotoxin (LPS 0.6 ng/kg) or placebo. Stimulation resulted in a peak response in pro-inflammatory cytokines after 90–120 min. Ninety minutes after injection, both perceived health framed to represent current (“How is your health right now?”) and global health (“How would you rate your general state of health”?) was significantly lower in the endotoxin condition (p’s < .01). The effect of endotoxin on self-rated health was mediated by sickness behavior as assessed by a newly developed questionnaire, Sickness Questionnaire, to 91% for current and 68 % for global health. In conclusion, it is demonstrated that a transient inflammatory activation, likely working through symptoms of sickness behavior, affects both subjectively perceived health for the moment as well as how health status on the more general level is appraised.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Sundelin, Tina, et al.
(author)
-
Sick man walking : Perception of health status from body motion
- 2015
-
In: Brain, behavior, and immunity. - : Elsevier BV. - 0889-1591 .- 1090-2139. ; 48, s. 53-56
-
Journal article (peer-reviewed)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.
|
|
| 18. |
|
|
