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Sumatriptan was introduced in 1983, as the first of the triptans, selective 5-hydroxytryptamine (5-HT ) receptor agonists, to treat moderate to severe migraine. Migraine predominates in females. Although there have been reports of sex differences in migraine-associated features and pharmacokinetics (PKs) of some triptans, sex differences in the PKs of oral sumatriptan have never been evaluated in Korean. We conducted this study of oral sumatriptan to assess the sex differences in Korean population. Thirty-eight healthy Korean subjects who participated in two separate clinical studies receiving a single oral dose of 50 mg sumatriptan with the same protocols were included in this analysis. A total of 532 sumatriptan concentration observations were used for a population PK modeling. Validation of final population PK model of sumatriptan was performed using bootstrap and visual predictive check. The PK profile of oral sumatriptan was adequately described by a one-compartmental model with combined transit compartment model and a first-order absorption. The covariate analysis showed that the clearance of oral sumatriptan was significantly higher in males than in females (male: 444 L/h, female: 281 L/h). Our results showed that there were sex differences in the clearance of oral sumatriptan. These results encourage further studies to establish the sumatriptan pharmacokinetic-pharmacodynamic (PK-PD) model considering sex-related PK differences, which may help to determine optimal dosing regimens for effective treatment of migraine in males and females. This article is protected by copyright. All rights reserved.
Learn More >There is a lack of clinically relevant measures for quantification of maladaptive mechanisms of the nociceptive system leading to chronic pain. Recently, we developed a method that tracks nociceptive detection thresholds (NDTs) using intraepidermal electrical stimulation. In this study, we explored the feasibility of using this NDT method in patients with persistent spinal pain syndrome type 2 (PSPS-T2) and its potential to enable observation of altered nociceptive processing induced by dorsal root ganglion (DRG) stimulation. In addition, we compared NDTs with quantitative sensory testing (QST) measurements and numeric rating scale (NRS).
Learn More >There is a pressing need for more effective nonaddictive treatment options for pain. Pain signals are transmitted from the periphery into the spinal cord via dorsal root ganglion (DRG) neurons, whose excitability is driven by voltage-gated sodium (Na) channels. Three Na channels (Na1.7, Na1.8, and Na1.9), preferentially expressed in DRG neurons, play important roles in pain signaling in humans. Blockade of these channels may provide a novel approach to the treatment of pain, but clinical translation of preclinical results has been challenging, in part due to differences between rodent and human DRG neurons. Human DRG neurons and iPSC-derived sensory neurons (iPSC-SNs) provide new preclinical platforms that may facilitate the development of novel pain therapeutics.
Learn More >Monoclonal antibodies anti-calcitonin gene-related peptide (mAbs anti-CGRP) pathway are effective and safe on migraine prevention. However, some drug agencies limited these treatments to one year due to their high costs. This study aimed at evaluating the effect of discontinuing mAbs anti-CGRP on monthly migraine days (MMDs) and disability in high-frequency episodic (HFEM) and chronic migraine (CM) patients.
Learn More >Headache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity.
Learn More >Migraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages. Thus, understanding this burden and the efficacy of migraine preventive medications in both sexes and across age groups is critical. The randomized, placebo-controlled, double-blind, phase 3b FOCUS study demonstrated the safety and efficacy of fremanezumab, a fully humanized monoclonal antibody (IgG2∆a) that selectively targets calcitonin gene-related peptide as a migraine preventive treatment for individuals with migraine and prior inadequate response to 2 to 4 migraine preventive medication classes. Here, we assessed the efficacy of fremanezumab in participants from FOCUS subgrouped by age (18-45 years and > 45 years) and sex.
Learn More >Rheumatoid arthritis (RA) is a chronic autoimmune disease that can result in considerable disability and pain. The metacarpophalangeal (MCP) joint is the most common diseased joint in RA. In clinical practice, MCP synovitis is commonly diagnosed on the basis of musculoskeletal ultrasound (MSUS) images. However, because of the vague criteria, the consistency in grading MCP synovitis based on MSUS images fluctuates between ultrasound imaging practitioners. Therefore, a new method for diagnosis of MCP synovitis is needed. Deep learning has developed rapidly in the medical area, which often requires a large-scale data set. However, the total number of MCP-MSUS images fell far short of the demand, and the distribution of different medical grades of images was unbalanced. With use of the traditional image augmentation methods, the diversity of the data remains insufficient. In this study, a high-resolution generative adversarial network (HRGAN) method that generates enough images for network training and enriches the diversity of the training data set is described. In comparison experiments, our proposed diagnostic system based on MSUS images provided more consistent results than those provided by clinical physicians. As the proposed method is image relevant, this study might provide a reference for other medical image classification research with insufficient data sets.
Learn More >This study aims to observe the effects of direct suppression of the parabrachial nucleus (PBN) on chronic neuropathic pain (CNP) and CNP-related behaviors in mice.
Learn More >The primary aim of this study was to review the effect of exercise in comparison with a non-active treatment on pain intensity, frequency of headache episodes, headache duration, quality of life, medication use, and psychological symptoms, in patients with migraine or tension-type headache (TTH). A systematic search was conducted in various electronic databases to identify all relevant studies: Medline (PubMed), PEDro, EBSCO and Google Scholar. Clinical trials assessing the effects of exercise interventions in patients with primary headaches were selected. Methodological quality was evaluated using the Cochrane Risk of Bias Tool and PEDro scale and qualitative analysis was based on classifying the results into levels of evidence according to the GRADE. 19 studies (2776 participants; 85% female) were included. The meta-analysis showed statistically significant differences in pain intensity for aerobic training in patients with migraine (SMD=-0.65; 95% CI=-1.07 to -0.22, very low certainty evidence) and for strength training in patients with TTH (SMD=-0.84; 95% CI=-1.68 to -0.01, very low certainty evidence). Statistically significant differences were also found in the medication use (SMD=-0.51; 95% CI=-0.85 to -0.17, low certainty evidence). Low transparency, replicability and high risk of bias were found. Aerobic training has a small to moderate clinical effect on pain intensity and medication use on migraine patients, with very low to low certainty of evidence. Strength training showed a moderate clinical effect with very low quality of evidence in patients with TTH. Exercise could be considered as clinically relevant for the management of patients with primary headaches, but the presence of low certainty of evidence and low transparency and replicability limited its clinical application. Perspective: This article presents current evidence about exercise interventions in patients with primary headaches, including migraine and tension-type headache. Existing findings are reviewed, and relevant data are provided on the effectiveness of each exercise modality, as well as its certainty of evidence and clinical applicability.
Learn More >Diabetic peripheral neuropathy (DPN) is a common condition that is associated with neuromuscular dysfunction and peripheral sensory impairment. These deficits predispose patients to sensory and motor system limitations, foot ulcers and a high risk of falls. Exercise training has been proposed as an effective tool to alleviate neural deficits and improve whole-body function. Here we review the effects of DPN on neuromuscular function, the mechanisms underlying this impairment, and the neural and muscular adaptations to exercise training. Muscle dysfunction is an early hallmark of DPN. Deficits in muscle strength, power, mass and a greater fatigability are particularly severe in the lower extremity muscles. Non-enzymatic glycation of motor proteins, impaired excitation-contraction coupling and loss of motor units have been indicated as the main factors underlying muscular dysfunction. Among the exercise-based solutions, aerobic training improves neural structure and function and ameliorates neuropathic signs and symptoms. Resistance training induces marked improvement of muscle performance and may alleviate neuropathic pain. A combination of aerobic and resistance training (i.e., combined training) restores small sensory nerve damage, reduces symptoms, and improves muscle function. The evidence so far suggests that exercise training is highly beneficial and should be included in the standard care for DPN patients.
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