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- Lind, Anne-Li, et al.
(författare)
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Affinity Proteomics Applied to Patient CSF Identifies Protein Profiles Associated with Neuropathic Pain and Fibromyalgia
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Objective: Today, there are no biological tests on which to base pain diagnoses, treatment choices or to understand the biological processes underlying and accompanying chronic pain for the individual pain patient. Relevant biological markers would greatly aid in diagnosis and treatment of patients with chronic pain. Our study aimed to find proteins in CSF associated with fibromyalgia and neuropathic pain, two common and poorly understood chronic pain conditions.Methods: We have performed CSF protein profiling of 55 proteins using a 100-plex antibody suspension bead array. We collected, analyzed and compared CSF samples from 25 patients with neuropathic pain (two independent sets, n=14 patients for discovery and n=11 for verification), 40 patients with fibromyalgia and 135 controls without neurological disease from two different populations.Results: We found significant differences in CSF protein levels between patients and controls (p<0.05). Among these proteins, Apolipoprotein C1 (APOC1) was found to be increased in CSF of neuropathic pain patients compared to controls and there was a non-significant trend for increased levels also in fibromyalgia patient CSF. Ectonucleotide pyrophosphatase (ENPP2, Autotaxin) was increased in the CSF of fibromyalgia patients compared to all other groups including neuropathic pain patients. Multivariate analysis revealed partially overlapping and partially distinct CSF profiles in neuropathic pain patients compared with fibromyalgia and controls for several other proteins including angiotensinogen (AGT), prostaglandin-H2 D-isomerase (PTGDS), neurexin-1 (NRXN1), superoxide dismutase 1 (SOD1) and superoxide dismutase 3 (SOD3).Conclusions: Our results, suggest that the CSF protein profiles of neuropathic pain and fibromyalgia patients may be different from each other and from those of controls. CSF levels of APOC1, ENPP2, AGT, PTGDS, NRXN1, SOD1 and SOD3 should be further investigated for their potential to serve as biomarkers of different kinds of pain pathophysiology.
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- Ihse, Elisabet, 1977-, et al.
(författare)
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Amyloid fibrils with fragmented ATTR may be the rule in non-Val30Met ATTR amyloidosis
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one composed of only intact ATTR (type B). Patients with type A fibrils have a late age of onset and signs of cardiomyopathy, while patients with type B fibrils have an early onset and much less myocardial involvement. The present study aimed to determine if the correlation between fibril type and clinical phenotype is true for familial amyloidosis in general. Cardiac and/or adipose tissue from 48 patients carrying 21 different non-TTRV30M mutations were examined, as well as 7 non-Swedish ATTRV30M patients. Fibril type was determined with western blotting and compared to the patients´ age of onset and degree of cardiomyopathy. Non-Swedish V30M patients showed the same correlation as described for Swedish V30M patients, with fibrils of only full-length ATTR (type B) linked to less myocardial involvement. In contrast, all patients with non-V30M mutations had a fibril composition with ATTR fragments (type A). Some of these patients had onset of disease at young age. The vast majority had increased thickness of left cardiac ventricle, but a few individuals had values within normal limits. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis. It also suggests that fibrils composed of only full-length ATTR is an exception, perhaps only found among young ATTRV30M amyloidosis patients.
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- Kaltsouni, Elisavet, et al.
(författare)
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Selective progesterone receptor modulation and brain activity at rest in patients with premenstrual dysphoric disorder
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Ovarian hormones have been indicated to impact brain connectivity and mood. However, there is no consistent evidence on hormone-dependent functional connectivity and mental health. Alterations in resting state networks have been suggested as markers of affective disorders, but only preliminary evidence is provided on premenstrual dysphoric disorder, in which symptoms occur upon fluctuations of ovarian hormones. Recently, three-month low-dose selective progesterone receptor modulator (SPRM) administration has been associated with symptom relief and altered task-based brain reactivity during a reactive aggression condition. The present study sought to investigate the effect of this treatment on resting state functional connectivity (rs-FC) in patients with PMDD. Seed-based analyses were conducted, including including seeds from the classic resting state networks along with the functional cluster affected by SPRM treatment. Within previously identified networks related with emotional processing, rs-FC was compared between individuals with PMDD during the symptomatic luteal phase before randomization to treatment or placebo and during the end of the last treatment cycle. Seed-based rs-FC analyses yielded significant treatment by time effects on rs-FC between the left posterior superior temporal gyrus and the right insula cortex, between the posterior cerebellum and the left temporal pole, and between the right lateral visual network and left superior frontal gyrus. Visuo-frontal luteal phase connectivity decreased for the SPRM group and was positively correlated with changes in mood symptom severity in the placebo group. Cerebellar and temporal connectivity increased for the SPRM treatment group, while temporo-insular connectivity decreased and was positively correlated with cortisol levels. These findings indicate that SPRM treatment influenced rs-FC, which could be a relevant mechanism behind symptom alleviation.
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