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Getting closer to a cure for migraine.

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Assessment of Changes in the Geographical Distribution of Opioid-Related Mortality Across the United States by Opioid Type, 1999-2016.

As the opioid epidemic evolves, it is vital to identify changes in the geographical distribution of opioid-related deaths, and the specific opioids to which those deaths are attributed, to ensure that federal and state public health interventions remain appropriately targeted.

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Lacosamide in patients with Nav1.7 mutations-related small fibre neuropathy: a randomized controlled trial.

Symptomatic treatment of neuropathic pain in small fibre neuropathy is often disappointing. The finding of voltage-gated sodium channel mutations in small fibre neuropathy (with mutations in SCN9A, encoding for Nav1.7) being most frequently reported suggest a specific target for therapy. The anticonvulsant lacosamide acts on Nav1.3, Nav1.7, and Nav1.8. The aim of this study was to evaluate the efficacy, safety, and tolerability of lacosamide as a potential treatment for pain in Nav1.7-related small fibre neuropathy. The Lacosamide-Efficacy-'N'-Safety in SFN (LENSS) was a randomized, placebo-controlled, double-blind, crossover-design study. Subjects were recruited in the Netherlands between November 2014 and July 2016. Patients with Nav1.7-related small fibre neuropathy were randomized to start with lacosamide followed by placebo or vice versa. In both 8-week treatment phases, patients received 200 mg two times a day (BID), preceded by a titration period, and ended by a tapering period. The primary outcome was efficacy, defined as the proportion of patients with 1-point average pain score reduction compared to baseline using the Pain Intensity Numerical Rating Scale. The trial is registered with ClinicalTrials.gov, number NCT01911975. Twenty-four subjects received lacosamide, and 23 received placebo. In 58.3% of patients receiving lacosamide, mean average pain decreased by at least 1 point, compared to 21.7% in the placebo group [sensitivity analyses, odds ratio 5.65 (95% confidence interval: 1.83-17.41); P = 0.0045]. In the lacosamide group, 33.3% reported that their general condition improved versus 4.3% in the placebo group (P-value = 0.0156). Additionally, a significant decrease in daily sleep interference, and in surface pain intensity was demonstrated. No significant changes in quality of life or autonomic symptoms were found. Lacosamide was well tolerated and safe in use. This study shows that lacosamide has a significant effect on pain, general wellbeing, and sleep quality. Lacosamide was well tolerated and safe, suggesting that it can be used for pain treatment in Nav1.7-related small fibre neuropathy.

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Towards personalized medicine in preterm newborns: Morphine analgesia predicted by genotype.

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Potentially Unsafe Chronic Medication Use among Older Adult Chronic Opioid Users.

To assess chronic potentially unsafe medication use among older adults using opioids chronically versus those who did not, to assess the likelihood of chronically using medications to treat adverse effects associated with chronic opioid use, and to characterize the differences in chronic potentially unsafe medication use at three morphine equivalent dose (MED) levels/day (<50MED, 50-90MED, and >90MED).

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Association Between Predeployment Optimism and Onset of Postdeployment Pain in US Army Soldiers.

Pain after deployment is a major health care concern. While risk factors have been previously studied, few studies have explored protective factors.

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Understanding the evidence for medical cannabis and cannabis-based medicines for the treatment of chronic non-cancer pain.

The use of medical cannabis and cannabis-based medicines has received increasing interest in recent years; with a corresponding surge in the number of studies and reviews conducted in the field. Despite this growth in evidence, the findings and conclusions of these studies have been inconsistent. In this paper, we outline the current evidence for medical cannabis and cannabis-based medicines in the treatment and management of chronic non-cancer pain. We discuss limitations of the current evidence, including limitations of randomised control trials in the field, limits on generalisability of previous findings and common issues such as problems with measurements of dose and type of cannabinoids. We discuss future directions for medicinal cannabinoid research, including addressing limitations in trial design; developing frameworks to monitor for use disorder and other unintended outcomes; and considering endpoints other than 30% or 50% reductions in pain severity.

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Phantom limb pain intensity is associated with generalized hyperalgesia.

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Anti-NGF treatment can reduce chronic neuropathic pain by changing peripheral mediators and brain activity in rats.

Neuropathic pain is driven by abnormal peripheral and central processing, and treatments are insufficiently effective. Antibodies against nerve growth factor (anti-NGF) have been investigated as a potent analgesic treatment for numerous conditions. However, the peripheral and brain effects of anti-NGF in neuropathic pain remain unknown. We examined the effectiveness of anti-NGF in reducing chronic pain by local administration in a rat model of sciatic constriction injury (CCI). NGF and substance P in the dorsal root ganglion (DRG) and spinal cord were evaluated. Neuronal activation was measured using c-Fos in the anterior cingulate cortex and ventrolateral periaqueductal gray. At 14 days after CCI, anti-NGF promoted a significant dose-dependent improvement in mechanical threshold, thermal withdrawal latency, and cold sensitivity, lasting for 5 h. NGF upregulation in the DRG and spinal cord after CCI was decreased by anti-NGF, while substance P was increased only in the DRG, and the treatment reduced it. Anti-NGF induced a significant reduction of neuronal activation in the anterior cingulate cortex, but not in the ventrolateral periaqueductal gray. This study provides the first evidence of the anti-NGF effects on brain activity. Thus, our findings suggest that anti-NGF improves chronic neuropathic pain, acting directly on peripheral sensitization and indirectly on central sensitization.

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Effects of onabotulinumtoxinA treatment in chronic migraine patients with and without daily headache at baseline: results from the COMPEL Study.

OnabotulinumtoxinA is effective in preventing chronic migraine (CM); however, the benefit of onabotulinumtoxinA in patients with CM with daily headache is unknown because these patients are typically excluded from clinical trials. This subanalysis of the COMPEL Study assessed the efficacy and safety of onabotulinumtoxinA in people with CM with and without daily headache.

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