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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.

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.

Are signs of central sensitisation in acute low back pain a precursor to poor outcome?

Central sensitisation is considered to have a pathophysiological role in chronic low back pain (LBP). Whether individuals with increased central sensitisation early in their condition are more likely to develop persistent pain or whether it increases over time is unclear. This study aimed to determine whether sensory profiles during acute LBP differ between individuals who did and did not recover by 6-months and to identify subgroups associated with outcomes. Individuals with acute LBP (<2 weeks of onset, N=99) underwent pain threshold (heat/cold/pressure) and conditioned pain modulation (CPM) testing after completing questionnaires related to pain/disability, sleep, and psychological status. Sensory measures were compared during the acute phase (baseline) and longitudinally (baseline/6-months) between unrecovered (≥pain and disability), partially recovered (<pain and/or disability), and recovered (no pain and disability) participants at 6-months. We assessed baseline patterns of sensory sensitivity alone, and with psychological and sleep data, using hierarchical clustering and related the clusters to outcome (pain/disability) at 3- and 6-months. No sensory measure at either time-point differed between groups. Two subgroups were identified that associated with more ("high sensitivity") or less ("high sensitivity and negative psychological state") recovery. These data appear to suggest that central sensitisation during the acute-phase resolves for many, but is a precursor to the transition to chronicity when combined with other psychological features. Perspective: Central sensitisation signs during early-acute low back pain does not necessarily precede poor outcome, but may be sustained in conjunction with other psychological factors and facilitate pain persistence.

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.

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.

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.

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.

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

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

The Portuguese 35-item Survey of Pain Attitudes applied to Portuguese women with Endometriosis.

Background and aims Endometriosis is a gynecologic recurring persistent condition affecting from 8% to 15% of premenopausal women worldwide. About 80% of women with endometriosis have at least one form of chronic pain – a multidimensional experience influenced by a number of psychosocial factors, including pain-related beliefs. The Survey of Pain Attitudes is the most commonly used measure of pain-related beliefs. This study aims to evaluate the psychometric properties of a Portuguese version of a brief version of the SOPA (the SOPA-35) in a sample of Portuguese women with Endometriosis. Methods A sample of 199 Portuguese women with Endometriosis provided demographic and pain history information, and completed a Portuguese version of the SOPA-35 and measures of pain intensity, disability, and psychological function. Analyses were performed to evaluate the factor structure of the Portuguese SOPA-35 items as well as the internal consistency, composite reliability, convergent validity, and concurrent validity of the scale scores. Results Confirmatory factor analysis supported a six-factor solution for a 19-item version of the Portuguese version of the Survey of Pain Attitudes (SOPA-19-P). The six scales evidenced marginal to good reliability (Cronbach's alphas: between 0.60 and 0.84; composite reliability: between 0.61 and 0.84). Four scales evidenced acceptable to good convergent validity (AVE: between 0.51 and 0.63). The findings also supported the concurrent validity of the SOPA-19-P. Conclusions The results support the use of the Portuguese SOPA-19-P for research and clinical purposes with Portuguese women in chronic pain due to endometriosis. Future research is warranted to further develop a European Portuguese version of SOPA. Implications The findings provide psychometric information about the SOPA-19-P. The results are helpful to researchers wishing to study the role of pain-related beliefs and their association with adjustment and treatment outcomes in women with chronic pain due to endometriosis.

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