| 1. |
- Bouhassira, Didier, et al.
(författare)
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Neuropathic pain phenotyping as a predictor of treatment response in painful diabetic neuropathy : data from the randomized, double-blind, COMBO-DN study.
- 2014
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 155:10, s. 2171-9
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Tidskriftsartikel (refereegranskat)abstract
- Sensory profiles are heterogeneous in neuropathic pain disorders, and subgroups of patients respond differently to treatment. To further explore this, patients in the COMBO-DN study were prospectively assessed by the Neuropathic Pain Symptom Inventory (NPSI) at baseline, after initial 8-week therapy with either duloxetine or pregabalin, and after subsequent 8-week combination/high-dose therapy. Exploratory post hoc cluster analyses were performed to identify and characterize potential subgroups through their scores in the NPSI items. In patients not responding to initial 60 mg/d duloxetine, adding 300 mg/d pregabalin for combination treatment was particularly effective regarding the dimensions pressing pain and evoked pain, whereas maximizing the duloxetine dose to 120 mg/d appeared more beneficial regarding paresthesia/dysesthesia. In contrast, adding 60 mg/d duloxetine to 300 mg/d pregabalin in case of nonresponse to initial pregabalin led to numerically higher decreases in all NPSI dimensions/items compared to maximizing the pregabalin dose to 600 mg/d. Cluster analysis revealed 3 patient clusters (defined by baseline scores for the 10 NPSI sensory items) with different pain profiles, not only in terms of overall pain severity, but also across NPSI items. Mean Brief Pain Inventory average pain improved in all clusters during combination/high-dose therapy. However, in patients with severe pain, the treatment effect showed a trend in favor of high-dose monotherapy, whereas combination therapy appeared to be more beneficial in patients with moderate and mild pain (not significant). These complementary exploratory analyses further endorse the idea that sensory phenotyping might lead to a more stratified treatment and potentially to personalized pain therapy.
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| 2. |
- Jensen, Karin B, et al.
(författare)
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Anxiety and depressive symptoms in fibromyalgia are related to poor perception of health but not to pain sensitivity or cerebral processing of pain.
- 2010
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 62:11, s. 3488-95
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Mood disturbance is common among patients with fibromyalgia (FM), but the influence of psychological symptoms on pain processing in this disorder is unknown. We undertook the present study to investigate the differential effect of depressive symptoms, anxiety, and catastrophizing on 1) pain symptoms and subjective ratings of general health status and 2) sensitivity to pain and cerebral processing of pressure pain.METHODS: Eighty-three women (mean ± SD age 43.8 ± 8.1 years) who fulfilled the American College of Rheumatology 1990 criteria for the classification of FM participated in the study. Patients rated pain intensity (100-mm visual analog scale [VAS]), severity of FM (Fibromyalgia Impact Questionnaire), general health status (Short Form 36), depressive symptoms (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), and catastrophizing (Coping Strategies Questionnaire). Experimental pain in the thumb was induced using a computer-controlled pressure stimulator. Event-related functional magnetic resonance imaging was performed during administration of painful stimuli representing 50 mm on a pain VAS, as well as nonpainful pressures.RESULTS: A correlation analysis including all self-ratings showed that depressive symptoms, anxiety, and catastrophizing scores were correlated with one another (P < 0.001), but did not correlate with ratings of clinical pain or with sensitivity to pressure pain. However, the subjective rating of general health was correlated with depressive symptoms and anxiety (P < 0.001). Analyses of imaging results using self-rated psychological measures as covariates showed that brain activity during experimental pain was not modulated by depressive symptoms, anxiety, or catastrophizing.CONCLUSION: Negative mood in FM patients can lead to a poor perception of one's physical health (and vice versa) but does not influence performance on assessments of clinical and experimental pain. Our data provide evidence that 2 partially segregated mechanisms are involved in the neural processing of experimental pain and negative affect.
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| 3. |
- Jensen, Karin B, et al.
(författare)
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Evidence of dysfunctional pain inhibition in Fibromyalgia reflected in rACC during provoked pain.
- 2009
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Ingår i: Pain. - : Ovid Technologies (Wolters Kluwer Health). - 0304-3959 .- 1872-6623. ; 144:1-2, s. 95-100
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Tidskriftsartikel (refereegranskat)abstract
- Over the years, many have viewed Fibromyalgia syndrome (FMS) as a so-called "functional disorder" and patients have experienced a concomitant lack of interest and legitimacy from the medical profession. The symptoms have not been explained by peripheral mechanisms alone nor by specific central nervous system mechanisms. In this study, we objectively evaluated the cerebral response to individually calibrated pain provocations of a pain-free body region (thumbnail). The study comprised 16 female FMS patients and 16 individually age-matched controls. Brain activity was measured using functional magnetic resonance imaging (fMRI) during individually calibrated painful pressures representing 50 mm on a visual analogue scale (VAS) ranging from 0 to 100 mm. Patients exhibited higher sensitivity to pain provocation than controls as they required less pressure to evoke equal pain magnitudes (U(A)=48, p<.002). Despite lower pressures applied in patients at VAS 50 mm, the fMRI-analysis revealed no difference in activity in brain regions relating to attention and affect or regions with sensory projections from the stimulated body area. However, in the primary link in the descending pain regulating system (the rostral anterior cingulate cortex) the patients failed to respond to pain provocation. The attenuated response to pain in this brain region is the first demonstration of a specific brain region where the impairment of pain inhibition in FMS patients is expressed. These results validate previous reports of dysfunctional endogenous pain inhibition in FMS and advance the understanding of the central pathophysiologic mechanisms, providing a new direction for the development of successful treatments in FMS.
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| 4. |
- Jensen, Karin B, et al.
(författare)
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Overlapping structural and functional brain changes in patients with long-term exposure to fibromyalgia pain.
- 2013
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 65:12, s. 3293-303
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: There is vast evidence to support the presence of brain aberrations in patients with fibromyalgia (FM), and it is possible that central plasticity is critical for the transition from acute to chronic pain. The aim of the present study was to investigate the relationship between brain structure and function in patients with FM.METHODS: Functional connectivity of the brain during application of intermittent pressure-pain stimuli and measures of brain structure were compared between 26 patients with FM and 13 age- and sex-matched healthy controls. Magnetic resonance imaging (MRI) was performed to obtain high-resolution anatomic images and functional MRI scans of the brain, which were used for measurements of pain-evoked brain activity.RESULTS: FM patients displayed a distinct overlap between decreased cortical thickness, decreased brain volumes, and decreased functional regional coherence in the rostral anterior cingulate cortex. The morphometric changes were more pronounced with longer exposure to FM pain. In addition, there was evidence of an association between structural and functional changes in the mesolimbic areas of the brain and the severity of comorbid depression symptoms in FM patients.CONCLUSION: The combined integration of structural and functional measures allowed for a unique characterization of the impact of FM pain on the brain. These data may lead to the identification of early structural and functional brain alterations in response to pain, which could be used to develop markers for predicting the development of FM and other pain disorders.
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| 5. |
- Jensen, Karin B, et al.
(författare)
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Patients with fibromyalgia display less functional connectivity in the brain's pain inhibitory network.
- 2012
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Ingår i: Molecular Pain. - : SAGE Publications. - 1744-8069. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: There is evidence for augmented processing of pain and impaired endogenous pain inhibition in Fibromyalgia syndrome (FM). In order to fully understand the mechanisms involved in FM pathology, there is a need for closer investigation of endogenous pain modulation. In the present study, we compared the functional connectivity of the descending pain inhibitory network in age-matched FM patients and healthy controls (HC).We performed functional magnetic resonance imaging (fMRI) in 42 subjects; 14 healthy and 28 age-matched FM patients (2 patients per HC), during randomly presented, subjectively calibrated pressure pain stimuli. A seed-based functional connectivity analysis of brain activity was performed. The seed coordinates were based on the findings from our previous study, comparing the fMRI signal during calibrated pressure pain in FM and HC: the rostral anterior cingulate cortex (rACC) and thalamus.RESULTS: FM patients required significantly less pressure (kPa) to reach calibrated pain at 50 mm on a 0-100 visual analogue scale (p < .001, two-tailed). During fMRI scanning, the rACC displayed significantly higher connectivity to the amygdala, hippocampus, and brainstem in healthy controls, compared to FM patients. There were no regions where FM patients showed higher rACC connectivity. Thalamus showed significantly higher connectivity to the orbitofrontal cortex in healthy controls but no regions showed higher thalamic connectivity in FM patients.CONCLUSION: Patients with FM displayed less connectivity within the brain's pain inhibitory network during calibrated pressure pain, compared to healthy controls. The present study provides brain-imaging evidence on how brain regions involved in homeostatic control of pain are less connected in FM patients. It is possible that the dysfunction of the descending pain modulatory network plays an important role in maintenance of FM pain and our results may translate into clinical implications by using the functional connectivity of the pain modulatory network as an objective measure of pain dysregulation.
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| 6. |
- Jensen, Karin B, et al.
(författare)
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Segregating the cerebral mechanisms of antidepressants and placebo in fibromyalgia.
- 2014
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 15:12, s. 1328-37
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Antidepressant drugs are commonly used to treat fibromyalgia, but there is little knowledge about their mechanisms of action. The aim of this study was to compare the cerebral and behavioral response to positive treatment effects of antidepressants or placebo. Ninety-two fibromyalgia patients participated in a 12-week, double-blind, placebo-controlled clinical trial with milnacipran, a serotonin-norepinephrine reuptake inhibitor. Before and after treatment, measures of cerebral pain processing were obtained using functional magnetic resonance imaging. Also, there were stimulus response assessments of pressure pain, measures of weekly pain, and fibromyalgia impact. Following treatment, milnacipran responders exhibited significantly higher activity in the posterior cingulum compared with placebo responders. The mere exposure to milnacipran did not explain our findings because milnacipran responders exhibited increased activity also in comparison to milnacipran nonresponders. Stimulus response assessments revealed specific antihyperalgesic effects in milnacipran responders, which was also correlated with reduced clinical pain and with increased activation of the posterior cingulum. A short history of pain predicted positive treatment response to milnacipran. We report segregated neural mechanisms for positive responses to treatment with milnacipran and placebo, reflected in the posterior cingulum. The increase of pain-evoked activation in the posterior cingulum may reflect a normalization of altered default mode network processing, an alteration implicated in fibromyalgia pathophysiology.PERSPECTIVE: This study presents neural and psychophysical correlates to positive treatment responses in patients with fibromyalgia, treated with either milnacipran or placebo. The comparison between placebo responders and milnacipran responders may shed light on the specific mechanisms involved in antidepressant treatment of chronic pain.
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| 7. |
- Kosek, Eva, et al.
(författare)
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Lower Placebo Responses After Long-Term Exposure to Fibromyalgia Pain.
- 2017
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Ingår i: Journal of Pain. - : Elsevier BV. - 1526-5900 .- 1528-8447. ; 18:7, s. 835-843
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about placebo mechanisms in patients with chronic pain is scarce. Fibromyalgia syndrome (FM) is associated with dysfunctions of central pain inhibition, and because placebo analgesia entails activation of endogenous pain inhibition, we hypothesized that long-term exposure to FM pain would negatively affect placebo responses. In our study we examined the placebo group (n = 37, mean age 45 years) from a 12-week, randomized, double-blind, placebo-controlled trial investigating the effects of milnacipran or placebo. Twenty-two patients were classified as placebo nonresponders and 15 as responders, according to the Patient Global Impression of Change scale. Primary outcome was the change in pressure pain sensitivity from baseline to post-treatment. Secondary outcomes included ratings of clinical pain (visual analog scale), FM effect (Fibromyalgia Impact Questionnaire), and pain drawing. Among placebo responders, longer FM duration was associated with smaller reductions in pressure pain sensitivity (r = .689, P = .004), but not among nonresponders (r = -.348, P = .112). In our study we showed that FM duration influences endogenous pain regulation, because pain levels and placebo-induced analgesia were negatively affected. Our results point to the importance of early FM interventions, because endogenous pain regulation may still be harnessed at that early time. Also, placebo-controlled trials should take FM duration into consideration when interpreting results.PERSPECTIVE: This study presents a novel perspective on placebo analgesia, because placebo responses among patients with chronic pain were analyzed. Long-term exposure to fibromyalgia pain was associated with lower placebo analgesia, and the results show the importance of taking pain duration into account when interpreting the results from placebo-controlled trials.
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| 8. |
- Palmowski, Andriko, et al.
(författare)
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The Effect of Low-Dose Glucocorticoids Over Two Years on Weight and Blood Pressure in Rheumatoid Arthritis : Individual Patient Data From Five Randomized Trials
- 2023
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Ingår i: Annals of Internal Medicine. - 0003-4819 .- 1539-3704. ; 176:9, s. 1181-1189
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Tidskriftsartikel (refereegranskat)abstract
- Background: Weight gain and hypertension are well known adverse effects of treatment with high-dose glucocorticoids. Objective: To evaluate the effects of 2 years of low-dose glucocorticoid treatment in rheumatoid arthritis (RA). Design: Pooled analysis of 5 randomized controlled trials with 2-year interventions allowing concomitant treatment with disease-modifying antirheumatic drugs. Setting: 12 countries in Europe. Patients: Early and established RA. Intervention: Glucocorticoids at 7.5 mg or less prednisone equivalent per day. Measurements: Coprimary end points were differences in change from baseline in body weight and mean arterial pressure after 2 years in intention-to-treat analyses. Difference in the change of number of antihypertensive drugs after 2 years was a secondary end point. Subgroup and sensitivity analyses were done to assess the robustness of primary findings. Results: A total of 1112 participants were included (mean age, 61.4 years [SD, 14.5]; 68% women). Both groups gained weight in 2 years, but glucocorticoids led, on average, to 1.1 kg (95% CI, 0.4 to 1.8 kg; P < 0.001) more weight gain than the control treatment. Mean arterial pressure increased by about 2 mm Hg in both groups, with a between-group difference of -0.4 mm Hg (CI, -3.0 to 2.2 mm Hg; P = 0.187). These results were consistent in sensitivity and subgroup analyses. Most patients did not change the number of antihypertensive drugs, and there was no evidence of differences between groups. Limitation: Body composition was not assessed, and generalizability to non-European regions may be limited. Conclusion: This study provides robust evidence that low-dose glucocorticoids, received over 2 years for the treatment of RA, increase weight by about 1 kg but do not increase blood pressure.
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