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Shortcomings and missed potentials in the management of migraine patients – experiences from a specialized tertiary care center.

Migraine is a common and severely disabling neurological disorder affecting millions of patients in Europe. Despite the availability of evidence-based national and international guidelines, the management of migraine patients often remains poor, which is often attributed to a low availability of headache specialists. The aim of this study was to investigate the adherence to national guidelines and to assess the possible potential of optimized therapy regimens in migraine patients.

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Endogenous pain modulation in children with functional abdominal pain disorders.

Functional abdominal pain disorders (FAPDs) are common among young individuals. To date, relatively little is known regarding the function of the endogenous analgesic mechanisms in this vulnerable group. Therefore, this case-control study aimed to compare conditioned pain modulation (CPM), pressure algometry, and psychosocial variables in 39 young children (aged 6-12 years) with FAPD and 36 age- and sex-matched pain-free controls. Pressure algometry was used to assess pressure pain thresholds (PPTs) at both symptomatic (umbilicus) as remote (trapezius and tibia) test sites. Conditioned pain modulation was recorded as an increase in the PPT at the trapezius test site in response to experimental conditioning pain imposed by the cold pressor task (12 ± 1°C). The assessors were blinded to the diagnoses. Parent-proxy and/or self-reported questionnaires were used to assess child's pain intensity, functional disability, pain-related fear, and parental pain catastrophizing. Compared with pain-free controls, young children with FAPD showed lower PPTs at all test sites (P < 0.05), a lower CPM response (P = 0.02), more functional disability (P < 0.001), and pain-related fear (P < 0.001). Parents of children with FAPD catastrophized more about their child's pain than parents of healthy children (P < 0.001). No sex differences were found for the experimental pain measurements (P > 0.05), nor was there a significant correlation between the child- and parent-reported questionnaires and the CPM effect (P > 0.05). In summary, young children with FAPD demonstrated secondary hyperalgesia and decreased functioning of endogenous analgesia.

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Microdeletion in a FAAH pseudogene identified in a patient with high anandamide concentrations and pain insensitivity.

The study of rare families with inherited pain insensitivity can identify new human-validated analgesic drug targets. Here, a 66-yr-old female presented with nil requirement for postoperative analgesia after a normally painful orthopaedic hand surgery (trapeziectomy). Further investigations revealed a lifelong history of painless injuries, such as frequent cuts and burns, which were observed to heal quickly. We report the causative mutations for this new pain insensitivity disorder: the co-inheritance of (i) a microdeletion in dorsal root ganglia and brain-expressed pseudogene, FAAH-OUT, which we cloned from the fatty-acid amide hydrolase (FAAH) chromosomal region; and (ii) a common functional single-nucleotide polymorphism in FAAH conferring reduced expression and activity. Circulating concentrations of anandamide and related fatty-acid amides (palmitoylethanolamide and oleoylethanolamine) that are all normally degraded by FAAH were significantly elevated in peripheral blood compared with normal control carriers of the hypomorphic single-nucleotide polymorphism. The genetic findings and elevated circulating fatty-acid amides are consistent with a phenotype resulting from enhanced endocannabinoid signalling and a loss of function of FAAH. Our results highlight previously unknown complexity at the FAAH genomic locus involving the expression of FAAH-OUT, a novel pseudogene and long non-coding RNA. These data suggest new routes to develop FAAH-based analgesia by targeting of FAAH-OUT, which could significantly improve the treatment of postoperative pain and potentially chronic pain and anxiety disorders.

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Opioid use after hip fracture surgery: A Danish nationwide cohort study from 2005-2015.

There is currently a knowledge gap regarding persistent opioid use after hip fracture surgery. Thus, opioid use within a year after hip fracture surgery in patients with/without opioid use before surgery was examined.

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Application of amplitude of low‑frequency fluctuation to altered spontaneous neuronal activity in classical trigeminal neuralgia patients: A resting‑state functional MRI study.

Recent studies have reported structural and functional abnormalities in multiple brain regions of classical trigeminal neuralgia (CTN) patients. Differences in spontaneous neuronal activity between CTN patients and healthy subjects, however, remain unknown. The aim of the present study was to investigate alterations in brain activity by application of amplitude of low frequency fluctuation (ALFF), thus analyzing the correlation between durations of spontaneous pain intensity and ALFF values in CTN patients. A total of 28 CTN patients (male, n=12; female, n=16) and 28 healthy controls (HCs; male, n=12; female, n=16) matched for age and sex were enrolled. All subjects underwent resting‑state functional magnetic resonance imaging and changes in spontaneous brain activity were investigated using an ALFF method. Receiver operating characteristic (ROC) curve analysis was applied to differentiate ALFF values of CTN patients from HCs. Altered ALFF values and clinical manifestations were evaluated using Pearson's correlation analysis. ALFF values of the bilateral inferior cerebellum, bilateral fusiform gyrus, right precentral gyrus, left inferior temporal gyrus, right superior cerebellum, left inferior occipital gyrus and right superior occipital gyrus were significantly higher in CTN patients when compared to HCs. ROC curve analysis of each brain revealed a near‑perfect AUC accuracy. Pearson's correlation analysis revealed the visual analog scale of the right eye to be positively correlated with both left inferior temporal and occipital gyral findings, while episode duration likewise was positively associated with left inferior temporal gyral findings. CTN patients exhibited abnormal spontaneous activity in multiple brain regions closely related to pain regulation and perception, while VAS and CTN episode duration were positively correlated with ALFF signal values in some brain regions. The present findings provide further insight into the pathological mechanisms underlying CTN.

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Investigating the Causal Mechanisms of Symptom Recovery in Chronic Whiplash Associated Disorders Using Bayesian Networks.

The present study's objective is to understand the causal mechanisms underpinning the recovery of individuals with whiplash-associated disorders (WAD). We applied Bayesian Networks (BN) to answer two study aims: (1) to identify the causal mechanism(s) of recovery underpinning neck-specific exercise, and (2) quantify if the cyclical pathway of the fear avoidance model (FAM) is supported by the present data.

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Health-related quality of life change in patients treated at a multidisciplinary pain clinic.

Multidisciplinary pain management (MPM) is a generally-accepted method for treating chronic pain, but heterogeneous outcome measures provide only limited conclusions concerning its effectiveness. Therefore, further studies on the effectiveness of MPM are needed to identify subgroups of patients who benefit, or do not benefit, from these interventions. Our aim was to analyze health-related quality of life (HRQoL) changes after MPM and to identify factors associated with treatment outcomes.

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Early occupational intervention for people with low back pain in physically demanding jobs: A randomized clinical trial.

Occupational medicine seeks to reduce sick leave; however, evidence for an add-on effect to usual care is sparse. The objective of the GOBACK trial was to test whether people with low back pain (LBP) in physically demanding jobs and at risk of sick leave gain additional benefit from a 3-month complex intervention that involves occupational medicine consultations, a work-related evaluation and workplace intervention plan, an optional workplace visit, and a physical activity program, over a single hospital consultation and an MRI.

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Associations of self-report and actigraphy sleep measures with experimental pain outcomes in patients with temporomandibular disorder and healthy controls.

Discrepancies between self-reported and actigraphy sleep measures are common, producing ambiguity about which are better predictors of experimental pain outcomes. The current study tested if pain intensity during and situational pain catastrophizing following experimental pain were differentially predicted by self-reported or actigraphy sleep measures in patients with chronic temporomandibular disorder (TMJD) or healthy controls (HCs).

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Pain-related functional interference in patients with chronic neuropathic postsurgical pain: an analysis of registry data.

Although chronic postsurgical pain (CPSP) is a major health care problem, pain-related functional interference has rarely been investigated. Using the PAIN OUT registry, we evaluated patients' pain-related outcomes on the first postoperative day, and their pain-related interference with daily living (Brief Pain Inventory) and neuropathic symptoms (DN4: douleur neuropathique en 4 questions) at 6 months after surgery. Endpoints were pain interference total scores (PITS) and their association with pain and DN4 scores. Furthermore, possible risk factors associated with impaired function at M6 were analyzed by ordinal regression analysis with PITS groups (no to mild, moderate, and severe interference) as a dependent three-stage factor. Odds ratios with 95% confidence intervals were calculated. Of 2322 patients, 15.3% reported CPSP with an average pain score ≥3 (numeric rating scale 0-10). Risk for a higher PITS group increased by 190% (odds ratio [95% confidence interval]: 2.9 [2.7-3.2]; P < 0.001) in patients with CPSP, compared to without CPSP. A positive DN4 independently increased risk by 29% (1.3 [1.12-1.45]; P < 0.001). Preexisting chronic pain (3.6 [2.6-5.1]; P < 0.001), time spent in severe acute pain (2.9 [1.3-6.4]; P = 0.008), neurosurgical back surgery in males (3.6 [1.7-7.6]; P < 0.001), and orthopedic surgery in females (1.7 [1.0-3.0]; P = 0.036) were the variables with strongest association with PITS. Pain interference total scores might provide more precise information about patients' outcomes than pain scores only. Because neuropathic symptoms increase PITS, a suitable instrument for their routine assessment should be defined.

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