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Impairment of Inhibition of Trigeminal Nociception via Conditioned Pain Modulation in Persons with Migraine Headaches.

To assess conditioned pain modulation efficiency in persons with and without migraine headaches.

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Dopamine-beta-hydroxylase 19-bp insertion/deletion polymorphism affects medication overuse in patients with chronic migraine.

Dopamine-beta-hydroxylase (DBH) enzyme activity is modulated at the genetic level by the presence of several polymorphisms. Among these, the 19-bp insertion/deletion (I/D) polymorphism (rs72393728/rs141116007) was investigated in several genetic association studies for its correlation with the susceptibility to develop episodic migraine, but conflicting results were achieved. In the present study we analyzed this genetic variant in a carefully characterized population of migraineurs encompassing both episodic and chronic migraine (with and without medication overuse) with the aim to perform a replication study and verify any possible correlation with migraine endophenotypes. Genotyping of the DBH 19-bp I/D polymorphism was performed on 400 migraine patients and 204 healthy individuals. The associations between genotypic frequencies and the clinical and sociodemographic features of migraineurs were then investigated. The DBH 19-bp I/D polymorphism did not correlate with migraine susceptibility or most clinical variables, with the exception of a statistically significant correlation within the subgroup of patients affected by chronic migraine were the individuals carrying the deleted (D) allele were significantly more prone to abuse in analgesics. As a result of this finding, the DBH 19-bp I/D polymorphism does not influence migraine susceptibility, but it might contribute to the development of medication overuse in patient with chronic migraine.

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Impact of an Opioid Safety Initiative on Patients Undergoing Total Knee Arthroplasty: A Time Series Analysis.

Opioid overuse remains rampant even in hospitals, but whether administrative opioid safety initiatives reduce use remains unclear WHAT THIS ARTICLE TELLS US THAT IS NEW: The authors evaluated the effects of a Veterans Administration national Opioid Safety Initiative using interrupted time series analysis to compare trends before and after starting the initiativeThere was a trivial increase in pain scores, and a substantial reduction in patients with chronic preoperative and postoperative opioid prescriptions BACKGROUND:: The Opioid Safety Initiative decreased high-dose prescriptions across the Veterans Health Administration. This study sought to examine the impact of this intervention (i.e., the Opioid Safety Initiative) on pain scores and opioid prescriptions in patients undergoing total knee arthroplasty.

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The relationship between hippocampal volume, chronic pain, and depressive symptoms in older adults.

We aimed to test the hypothesis that the effect of chronic pain on depressive symptoms is mediated through hippocampal volume (HV). Participants were 131 non-demented adults over the age of 70 years from the Einstein Aging Study. Smaller right and left HV were both associated with higher depressive symptoms, but only smaller right HV was associated with chronic pain. In mediation models, right HV was a significant mediator for the effect of chronic pain on depression. Our findings suggest presence of a shared brain substrates between chronic pain and depression as reflected by right HV.

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Two randomized migraine studies of galcanezumab: Effects on patient functioning and disability.

To evaluate changes from baseline in patient-reported outcomes for measures of functioning and disability among patients with migraine treated with galcanezumab or placebo.

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Anoctamin 3: A Possible Link between Cluster Headache and Ca Signaling.

Cluster headache is a severe primary headache characterized by extremely painful attacks of unilateral headache. Verapamil is commonly used as a prophylactic treatment with good effect. In order to search for new pathways involved in the pathophysiology of cluster headache, we analyzed genetic variants that were previously linked to verapamil response in migraine in a Swedish cluster headache case-control sample. We used TaqMan qPCR for genetic screening and performed a gene expression analysis on associated genes in patient-derived fibroblasts, and further investigated which reference genes were suitable for analysis in fibroblasts from cluster headache patients. We discovered a significant association between , a gene encoding a calcium-activated ion channel, and cluster headache. The association was not dependent on verapamil treatment since the associated variant, rs1531394, was also overrepresented in patients not using verapamil. No difference was found in the gene expression between controls and patients. Also, we determined that , and were suitable reference genes in cluster headache fibroblasts. This finding is the first report of an association between a variant in a gene encoding an ion-channel and cluster headache, and the first significant genetic evidence of calcium involvement in cluster headache pathophysiology.

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nVNS sham significantly affects the trigeminal-autonomic reflex: A randomized controlled study.

To determine whether high placebo effects observed in recently published clinical noninvasive vagal nerve stimulation (nVNS) trials can be attributed to an active modulation of the trigeminal-autonomic reflex by the sham device.

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The Metabotropic Glutamate Receptor 5 Negative Allosteric Modulator Fenobam: Pharmacokinetics, Side Effects, and Analgesic Effects in Healthy Human Subjects.

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Uncoupling sodium channel dimers rescues phenotype of pain-linked Nav1.7 mutation.

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Field testing of the revised neuropathic pain grading system in a cohort of patients with neck and upper limb pain.

Background and aims In 2008, the International Association for the Study of Pain Special Interest Group on Neuropathic Pain (NeuPSIG) proposed a clinical grading system to help identify patients with neuropathic pain (NeP). We previously applied this classification system, along with two NeP screening tools, the painDETECT (PD-Q) and Leeds Assessment of Neuropathic Symptoms and Signs pain scale (LANSS), to identify NeP in patients with neck/upper limb pain. Both screening tools failed to identify a large proportion of patients with clinically classified NeP, however a limitation of our study was the use of a single clinician performing the NeP classification. In 2016, the NeuPSIG grading system was updated with the aim of improving its clinical utility. We were interested in field testing of the revised grading system, in particular in the application of the grading system and the agreement of interpretation of clinical findings. The primary aim of the current study was to explore the application of the NeuPSIG revised grading system based on patient records and to establish the inter-rater agreement of detecting NeP. A secondary aim was to investigate the level of agreement in detecting NeP between the revised NeuPSIG grading system and the LANSS and PD-Q. Methods In this retrospective study, two expert clinicians (Specialist Pain Medicine Physician and Advanced Scope Physiotherapist) independently reviewed 152 patient case notes and classified them according to the revised grading system. The consensus of the expert clinicians' clinical classification was used as "gold standard" to determine the diagnostic accuracy of the two NeP screening tools. Results The two clinicians agreed in classifying 117 out of 152 patients (ICC 0.794, 95% CI 0.716-850; κ 0.62, 95% CI 0.50-0.73), yielding a 77% agreement. Compared to the clinicians' consensus, both LANSS and PD-Q demonstrated limited diagnostic accuracy in detecting NeP (LANSS sensitivity 24%, specificity 97%; PD-Q sensitivity 53%, specificity 67%). Conclusions The application of the revised NeP grading system was feasible in our retrospective analysis of patients with neck/upper limb pain. High inter-rater percentage agreement was demonstrated. The hierarchical order of classification may lead to false negative classification. We propose that in the absence of sensory changes or diagnostic tests in patients with neck/upper limb pain, classification of NeP may be further improved using a cluster of clinical findings that confirm a relevant nerve lesion/disease, such as reflex and motor changes. The diagnostic accuracy of LANSS and PD-Q in identifying NeP in patients with neck/upper limb pain remains limited. Clinical judgment remains crucial to diagnosing NeP in the clinical practice. Implications Our observations suggest that in view of the heterogeneity in patients with neck/upper limb pain, a considerable amount of expertise is required to interpret the revised grading system. While the application was feasible in our clinical setting, it is unclear if this will be feasible to apply in primary health care settings where early recognition and timely intervention is often most needed. The use of LANSS and PD-Q in the identification of NeP in patients with neck/upper limb pain remains questionable.

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