| 1. |
- Jensen, Karin B, et al.
(författare)
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Cognitive Behavioral Therapy increases pain-evoked activation of the prefrontal cortex in patients with fibromyalgia.
- 2012
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 153:7, s. 1495-1503
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Tidskriftsartikel (refereegranskat)abstract
- Interventions based on Cognitive Behavioral Therapy (CBT) are widely used to treat chronic pain, but the brain mechanisms responsible for these treatment effects are poorly understood. The aim of this study was to validate the relevance of the cortical control theory in response to an exposure-based form of CBT, Acceptance and Commitment Therapy, in patients with chronic pain. Forty-three female patients diagnosed with fibromyalgia syndrome were enrolled in a randomized, 12-week, waiting-list controlled clinical trial (CBT n=25; controls n=18). CBT was administered in groups of six patients during 12 weekly sessions. Functional magnetic resonance imaging (fMRI) during pressure-evoked pain was assessed before and after treatment or the 12-week period. Self-report questionnaires of depression and anxiety were administered pre- and posttreatment as well as 3 months following end of treatment. Patients treated with CBT reported larger improvement of fibromyalgia on the Patient Global Impression of Change measure, and improved depression and anxiety symptoms, compared to the waiting-list controls. However, there were no effects on clinical pain or pain sensitivity measures. An analysis of fMRI scans revealed that CBT led to increased activations in the ventrolateral prefrontal/lateral orbitofrontal cortex; regions associated with executive cognitive control. We suggest that CBT changes the brain's processing of pain through an altered cerebral loop between pain signals, emotions, and cognitions; leading to increased access to executive regions for reappraisal of pain. Our data thereby support our hypothesis about the activation of a cortical control mechanism in response to CBT treatment in chronic pain.
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| 2. |
- Kadetoff, Diana, et al.
(författare)
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Evidence of central inflammation in fibromyalgia-increased cerebrospinal fluid interleukin-8 levels.
- 2012
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Ingår i: Journal of Neuroimmunology. - : Elsevier BV. - 0165-5728 .- 1872-8421. ; 242:1-2, s. 33-8
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Tidskriftsartikel (refereegranskat)abstract
- Activation of glia cells resulting in intrathecal elevation of cytokines and chemokines has been hypothesized in chronic pain syndromes such as fibromyalgia. To our knowledge, this is the first study assessing intrathecal concentrations of pro-inflammatory substances in fibromyalgia. We report elevated cerebrospinal fluid and serum concentrations of interleukin-8, but not interleukin-1beta, in FM patients. This profile is in accordance with FM symptoms being mediated by sympathetic activity rather than dependent on prostaglandin associated mechanisms and supports the hypothesis of glia cell activation in response to pain mechanisms.
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| 3. |
- Kadetoff, Diana, et al.
(författare)
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Evidence of reduced sympatho-adrenal and hypothalamic-pituitary activity during static muscular work in patients with fibromyalgia.
- 2010
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Ingår i: Journal of Rehabilitation Medicine. - : Medical Journals Sweden AB. - 1650-1977 .- 1651-2081. ; 42:8, s. 765-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenocortical axis during static exercise in patients with fibromyalgia.PATIENTS AND METHODS: Sixteen patients with fibromyalgia and 16 healthy controls performed a static knee extension until exhaustion. Plasma catecholamines, adrenocorticotropic hormone and cortisol, as well as blood pressure and heart rate, were assessed before, during and following contraction. Plasma C reactive protein was analysed at baseline.RESULTS: Blood pressure and heart rate increased during contraction (p < 0.001) and decreased following contraction (p < 0.001) in both groups alike. Compared with baseline, plasma catecholamines increased during contraction in both groups (p < 0.001), but patients with fibromyalgia had lower levels of plasma adrenaline (p < 0.04) and noradrenaline (p < 0.08) at all times. Adrenocorticotropic hormone increased at exhaustion in controls (p < 0.001), but not in patients with fibromyalgia, who also had lower adrenocorticotropic hormone at exhaustion (p < 0.02) compared with controls. There were no group differences, or changes over time in plasma cortisol. High sensitivity C reactive protein was higher in patients with fibromyalgia compared with controls (p < 0.02).CONCLUSION: Patients with fibromyalgia exhibited a hypoactive sympatho-adrenal system as well as a hypo-reactive hypothalamic-pituitary axis during static exercise.
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| 4. |
- Kadetoff, Diana
(författare)
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Implications of autonomic nervous system and central inflammatory parameters for the perception of pain in fibromyalgia patients
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Dysfunctions of the autonomic nervous system and of endogenous pain modulation have been reported in fibromyalgia (FM) patients. The dysregulation of the autonomic nervous system, i.e., increased sympathetic activity at baseline and hyporeactivity during exercise and stress, could contribute to muscle ischemia as well as to the exercise intolerance that is typically seen in FM patients. Isometric contractions are potent stimuli to provoke muscle ischemia, increased muscle pain, heart rate (HR) and blood pressure (BP). In our first two studies we used isometric contractions to investigate the interaction between cardiovascular regulation and pain perception and to assess activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis (HPA-axis) in FM patients. Glia cell activation has been suggested as a possible pathophysiological mechanism in FM and can be linked to dysfunction of autonomic nervous system. Increased levels of pro-inflammatory cytokines have been reported in the blood of FM patients, but cytokines have, to our knowledge, never been studied in the cerebrospinal fluid (CSF) in FM. In study three and four, we investigated pro-inflammatory cytokines in the CSF of patients with FM, rheumatoid arthritis (RA) and controls. In study 1 we assessed the interactions between cardiovascular regulation and pain perception during static muscle contractions in FM patients and healthy controls. We found that systolic and diastolic BP increased during contraction and decreased following contraction in both groups alike. A significant increase in HR was seen during contraction in FM patients, but not in healthy controls. The rated exertion/fatigue and pain intensity increased more during contraction and remained elevated longer following contraction in the patient group. Pressure pain thresholds (PPTs) were lower in patients compared to controls at all times. No group differences in PPT changes over time were found. In conclusion, no indication of an attenuated cardiovascular response to exercise was found in our FM patients. The more pronounced HR increase in patients during contraction was most likely due to de-conditioning. No exercise related change in PPTs was seen in either group, most likely due to insufficient exercise intensity, but the pain induced by contraction was more pronounced in FM patients. In study 2 we investigated activation of the sympathetic nervous system and the HPA-axis during static contractions in FM patients and healthy controls. BP and HR increased during contraction and decreased following contraction in both groups alike. Compared to baseline, plasma catecholamines increased during contraction in both groups alike but FM patients had lower levels of plasma adrenaline and a non-significant tendency to lower plasma noradrenaline at all times. No baseline group differences in adrenocorticotropic hormone (ACTH) were found. ACTH increased at exhaustion in controls, but not in FM patients and FM patients had lower ACTH at exhaustion compared to controls. High sensitivity C-reactive protein (CRP) was elevated in FM patients compared to controls. In conclusion, FM patients exhibited a hypoactive sympatho-adrenal system as well as a hypo-reactive HPA-axis during static exercise. In study 3 we assessed pro-inflammatory cytokines in the CSF and serum in FM patients and headache controls. We reported elevated CSF and serum concentrations of interleukin-8 (IL-8), but not IL-1b, in FM patients. Our conclusion was that the cytokine profile was in accordance with FM symptoms being mediated by abnormal activity in the sympathetic nervous system rather than dependent on prostaglandin associated mechanisms. The results support the hypothesis of glia cell activation in FM. In study 4 CSF and serum concentrations of pro- and anti-inflammatory cytokines in our FM cohort were compared to patients with an inflammatory rheumatic disease, i.e., rheumatoid arthritis (RA). We found different CSF cytokine profiles with higher concentrations of the pro-inflammatory IL-1b and lower concentrations of the anti-inflammatory IL-1Ra, IL-4 and IL-10 in the CSF of RA patients, compared to FM. FM patients had higher CSF and serum IL-8 concentrations than RA patients. Our results indicate different profiles of central cytokine release, i.e., IL-1b in patients with inflammatory, prostaglandin associated pain (RA) and IL-8 in patients with dysfunctional, possibly sympathetically mediated pain (FM).
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| 5. |
- Lampa, Jon, et al.
(författare)
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Peripheral inflammatory disease associated with centrally activated IL-1 system in humans and mice.
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 109:31, s. 12728-33
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Tidskriftsartikel (refereegranskat)abstract
- During peripheral immune activation caused by an infection or an inflammatory condition, the innate immune response signals to the brain and causes an up-regulation of central nervous system (CNS) cytokine production. Central actions of proinflammatory cytokines, in particular IL-1β, are pivotal for the induction of fever and fatigue. In the present study, the influence of peripheral chronic joint inflammatory disease in rheumatoid arthritis (RA) on CNS inflammation was investigated. Intrathecal interleukin (IL)-1β concentrations were markedly elevated in RA patients compared with controls or with patients with multiple sclerosis. Conversely, the anti-inflammatory IL-1 receptor antagonist and IL-4 were decreased in RA cerebrospinal fluid (CSF). Tumor necrosis factor and IL-6 levels in the CSF did not differ between patients and controls. Concerning IL-1β, CSF concentrations in RA patients were higher than in serum, indicating local production in the CNS, and there was a positive correlation between CSF IL-1β and fatigue assessments. Next, spinal inflammation in experimental arthritis was investigated. A marked increase of IL-1β, IL-18, and tumor necrosis factor, but not IL-6 mRNA production, in the spinal cord was observed, coinciding with increased arthritis scores in the KBxN serum transfer model. These data provide evidence that peripheral inflammation such as arthritis is associated with an immunological activation in the CNS in both humans and mice, suggesting a possible therapeutic target for centrally affecting conditions as fatigue in chronic inflammatory diseases, for which to date there are no specific treatments.
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