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The current study was performed to evaluate the effects of alpha-lipoic acid (ALA) supplementation on lactate, nitric oxide (NO), vascular cell adhesion molecule-1 (VCAM-1) levels, and clinical symptoms in women with episodic migraines. Considering the inclusion and exclusion criteria, ninety-two women with episodic migraines participated in this randomized, double-blind, placebo-controlled, parallel-design trial. The participants were randomly assigned to receive either 300 mg/day ALA or placebo, twice per day for 12 weeks. The primary outcomes included headache severity, headache frequency per month, and duration of attacks and the secondary outcomes included lactate (a marker of mitochondrial function), NO, and VCAM-1 serum levels were measured at baseline and the end of the intervention. At the end of the study, there was a significant decrease in lactate serum levels (- 6.45 ± 0.82 mg/dl vs – 2.27 ± 1.17 mg/dl; P = 0.039) and VCAM-1 (- 2.02 ± 0.30 ng/ml vs – 1.21 ± 0.36 ng/ml; P = 0.025) in the ALA as compared to the placebo group. In addition, the severity (P < 0.001), frequency (P = 0.001), headache impact test (HIT-6) (P < 0.001), headache dairy results (HDR) (P = 0.003), and migraine headache index score (MHIS) (P < 0.001) had significantly decreased in the intervention as compared to the control group. No significant changes were observed for NO levels and duration of migraine pains. ALA supplementation can be considered a potential adjunct treatment in patients with migraine due to its improving mitochondrial and endothelial functions and clinical symptoms.
Learn More >Disability and distress caused by chronic low back pain (LBP) lacking clear pathoanatomical explanations cause huge problems both for patients and society. A subgroup of patients has Modic changes (MC), identifiable by MRI as vertebral bone marrow lesions. The cause of such changes and their relationship to pain are not yet understood. We explored the pathobiology of these lesions using profiling of gene expression in blood, coupled with an edema-sensitive MRI technique known as short tau inversion recovery (STIR) imaging. STIR images and total RNA from blood were collected from 96 patients with chronic LBP and MC type I, the most inflammatory MC state. We found the expression of 37 genes significantly associated with STIR signal volume, ten genes with edema abundancy (a constructed combination of STIR signal volume, height, and intensity), and one gene with expression levels significantly associated with maximum STIR signal intensity. Gene sets related to interferon signaling, mitochondrial metabolism and defense response to virus were identified as significantly enriched among the upregulated genes in all three analyses. Our results point to inflammation and immunological defense as important players in MC biology in patients with chronic LBP.
Learn More >We have recently developed a mouse monoclonal antibody (12-10H) binding to the head domain region in rat P2X4 receptor (rP2X4R, which is crucial for the pathogenesis of neuropathic pain) expressed on the cell with the highest binding affinity (K = 20 nM). However, the 12-10H antibody failed to detect endogenously expressed P2X4Rs in microglia isolated from the spinal cord of rats whose spinal nerves were injured. Then, we prepared R5 mutant, in which five arginine residues were introduced into variable regions except for the "hot spot" in the 12-10H antibody to increase electrostatic interactions with the head domain, an anionic region, in rP2X4R. The mutation resulted in an increase of 50-fold in the affinity of the R5 mutant for the head domain with respect to the intact 12-10H antibody. As a result, detection of P2X4Rs endogenously expressed on primary cultured microglial cells originated from the neonatal rat brain and spinal cord microglia isolated from a rat model of neuropathic pain was achieved. These findings suggest a strategy to improve the affinity of a monoclonal antibody for an anionic antigen by the introduction of several arginine residues into variable regions other than the "hot spot" in the paratope.
Learn More >Ultrasound-guided hydrodissection with 5% dextrose in water (DW5) creates a peri-nervous compartment, separating the nerve from the neighboring anatomical structures. The aim of this randomized study was to determine the minimum volume of lidocaine 2% with epinephrine 1:200,000 required when using this technique to achieve an effective median nerve block at the elbow in 95% of patients (MEAV95). Fifty-two patients scheduled for elective hand surgery received an ultrasound-guided circumferential perineural injection of 4 ml DW5 and an injection of local anesthetic (LA) following a biased coin up-and-down sequential allocation method. A successful block was defined as a light touch completely suppressed on the two distal phalanges of the index finger within a 30-min evaluation period. The MEAV95 of lidocaine 2% with epinephrine was 4 ml [IQR 3.5-4.0]. Successful median nerve block was obtained in 38 cases (82.6%) with median onset time of 20.0 [10.0-21.2] minutes (95% CI 15-20). The analgesia duration was 248 [208-286] minutes (95% CI 222-276). Using an ultrasound-guided hydrodissection technique with DW5, the MEAV95 to block the median nerve at the elbow with 2% lidocaine with epinephrine was 4 ml [IQR 3.5-4.0]. This volume is close to that usually recommended in clinical practice.Trial registration clinicaltrials.gov. NCT02438657, Date of registration: May 8, 2015.
Learn More >Whiplash injury is common following road traffic crashes affecting millions worldwide, with up to 50% of the injured developing chronic symptoms and 15% having a reduced working capability due to ongoing disability. Many of these patients receive treatment in primary care settings based upon clinical and diagnostic imaging findings. Despite the identification of different types of injuries in the whiplash patients, clinically significant relationships between injuries and chronic symptoms remains to be fully established. This study investigated the feasibility of magnetic resonance imaging (MRI) techniques including quantitative diffusion weighted imaging and measurements of cerebrospinal fluid (CSF) flow as novel non-invasive biomarkers in a population of healthy volunteers and chronic whiplash patients recruited from a chiropractic clinic for the purpose of improving our understanding of whiplash injury.
Learn More >The synthetic chemical 1,4-dioxane is used as industrial solvent, food, and care product additive. 1,4-Dioxane has been noted to influence the nervous system in long-term animal experiments and in humans, but the molecular mechanisms underlying its effects on animals were not previously known.
Learn More >Objective Small area electrodes enable preferential activation of nociceptive fibers. It is debated, however, whether co-activation of large fibers still occurs for the existing electrode designs. Moreover, existing electrodes are limited to low stimulation intensities, for which behavioral and physiological responses may be considered less reliable. A recent optimization study showed that there is a potential for improving electrode performance and increase the range of possible stimulation intensities. Based on those results, the present study introduces and tests a novel planar concentric array electrode design for small fiber activation in healthy volunteers. Approach Volunteers received electrical stimulation with the planar concentric array electrode and a regular patch electrode. Perception thresholds were estimated at the beginning and the end of the experiment. Evoked cortical potentials were recorded in blocks of 30 stimuli. For the patch, stimulation intensity was set to two times perception threshold (PT), while three intensities, 2, 5, and 10 times PT, were applied with the planar concentric array electrode. Sensation quality, numerical-rating scores, and reaction times were obtained for each PT estimation and during each block of evoked potential recordings. Main results Stimulation with the patch electrode was characterized as dull, while stimulation with the planar concentric array electrode was characterized as sharp, with increased sharpness for increasing stimulus intensity. Likewise, NRS scores were higher for the planar concentric array electrode compared to the patch and increased with increasing stimulation intensity. Reaction times and ERP latencies were longer for the planar concentric array electrode compared to the patch. Significance The presented novel planar concentric array electrode is a small, non-invasive, and single-use electrode that has the potential to investigate small fiber neuropathy and pain mechanisms, as it is small fiber preferential for a wide range of stimulation intensities.
Learn More >Strong opioid analgesics, including morphine, are the mainstays for treating moderate to severe acute pain and alleviating chronic cancer pain. However, opioid-related adverse effects, including nausea or vomiting, sedation, respiratory depression, constipation, pruritus (itch), analgesic tolerance, and addiction and abuse liability, are problematic. In addition, the use of opioids to relieve chronic noncancer pain is controversial due to the "opioid crisis" characterized by opioid misuse or abuse and escalating unintentional death rates due to respiratory depression. Hence, considerable research internationally has been aimed at the "Holy Grail" of the opioid analgesic field, namely the discovery of novel and safer opioid analgesics with improved opioid-related adverse effects. In this Perspective, medicinal chemistry strategies are addressed, where structurally diverse nonmorphinan-based opioid ligands derived from natural sources were deployed as lead molecules. The current state of play, clinical or experimental status, and novel opioid ligand discovery approaches are elaborated in the context of retaining analgesia with improved safety and reduced adverse effects, especially addiction liability.
Learn More >Patients with chronic pain face several challenges in using clinical tools to help them monitor, understand, and make meaningful decisions about their pain conditions. Our group previously presented data on Painimation, a novel electronic tool for communicating and assessing pain.
Learn More >To explain the factors contributing to the gap in depression between employed arthritis patients with and without paid sick leave.
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