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The Relationship between Clinical and Quantitative Measures of Pain Sensitization in Knee Osteoarthritis.

Pain sensitization in knee osteoarthritis is associated with greater symptom severity and poorer clinical outcomes. Measures which identify pain sensitization and are accessible to use in clinical practice have been suggested to enable more targeted treatments. This merits further investigation. This study examines the relationship between Quantitative Sensory Testing (QST) and clinical measures of pain sensitization in people with knee osteoarthritis.

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Calcium-inducible MAPK/AP-1 signaling drives semaphorin 3A expression in normal human epidermal keratinocytes.

Epidermal keratinocytes express semaphorin (Sema) 3A, which is involved in the regulation of cutaneous innervation. However, the mechanisms underlying the intracellular signaling of Sema3A expression in keratinocytes remain unknown. We herein investigated signaling mechanisms for the induction of Sema3A expression in normal human epidermal keratinocytes (NHEKs). Sema3A expression transiently increased in calcium-stimulated NHEKs, but markedly decreased in terminally differentiated NHEKs. Sema3A mRNA mainly localized in the stratum basale and stratum suprabasale of the epidermis. The 5'-flanking region of the Sema3A gene was cloned, and a critical region for Sema3A promoter activity within -134 bp of the start codon was identified. Transcription factor binding sites, including that for activator protein (AP)-1, were found in this region. Sema3A expression was increased by the co-overexpression of JunB and Fra-2 in the presence of 0.1 or 1.4 mM calcium. The calcium-mediated transient up-regulation of Sema3A expression was significantly suppressed by mitogen-activated protein kinase [MAPK]/extracellular signal-regulated kinase [ERK] (MEK) 1/2 or AP-1 inhibitors. These results demonstrate that the calcium-mediated transient up-regulation of Sema3A in NHEKs is involved in the MEK/ERK and AP-1 signaling axis. Therefore, Sema3A mRNA may be expressed in the lower epidermis under controlled conditions by calcium via the MAPK-AP1 axis.

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Associations between migraine attacks and nightly sleep characteristics among adults with episodic migraine: a prospective cohort study.

Given the unknown immediate impact of migraine on nighttime sleep, we prospectively examined whether migraine headaches were associated with subsequent shorter sleep duration, higher fragmentation and poorer quality in a cohort of 98 adults with episodic migraine.

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Musculoskeletal pain in 6-year-old children: the Generation R Study.

Musculoskeletal (MSK) pain is frequently reported among adolescents and children and a common reason for consultation in primary care. Our aim is to examine its prevalence in 6-year old children in a general population and to assess associations with physical and psychosocial factors. Data from the Generation R Study, a population based cohort, was used. Prevalence and characteristics of MSK pain were assessed with parent-reported questionnaires at 6-years of age (N=6200). Demographics and data on physical activity, sedentary behaviors, previous reported MSK pain and behavioral problems were extracted from questionnaires. The BMI SD score was calculated from objectively measured weight and height. A three-month prevalence of 10.0% was found for MSK pain in children, of which one third was chronic, and 44.6% experienced together with pain at other sites. Univariate analyses showed that boys and children with lower socioeconomic status (SES) reported MSK pain more frequent compared to other pain and no pain. While no associations were found between MSK pain and children's BMI and physical activity level, children with MSK pain were more likely to watch television ≥2 hours/day. Multivariable analysis showed significant associations for MSK pain at 3 years of age (OR 5.10, 95% CI 3.25 to 7.98) and behavioral problems (OR 2.10, 95% CI 1.19 to 3.72) with the presence of MSK pain. So, MSK pain is already common in young children and is often chronic or recurrent. Previous reported MSK pain and behavioral problems are independently associated with MSK pain in the studied population.

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High-Dose Intravenous Immunoglobulin Is Effective in Painful Diabetic Polyneuropathy Resistant to Conventional Treatments. Results of a Double-Blind, Randomized, Placebo-Controlled, Multicenter Trial.

The efficacy and safety of high-dose intravenous immunoglobulin (IVIG) in treatment-resistant diabetic painful polyneuropathy (DPN) were assessed.

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Restoration of Somatosensory Function by Pairing Vagus Nerve Stimulation with Tactile Rehabilitation.

Sensory dysfunction is a common consequence of many forms of neurological injury, including stroke and nerve damage. Rehabilitative paradigms that incorporate sensory retraining can provide modest benefits, but the majority of patients are left with lasting sensory loss. We have developed a novel strategy that uses closed-loop vagus nerve stimulation (VNS) paired with tactile rehabilitation to enhance synaptic plasticity and facilitate recovery of sensory function.

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Management of patients with a musculoskeletal pain condition that is likely chronic: Results from a national cross sectional survey.

The purpose of the study was to explore clinical management for new cases of musculoskeletal pain that are likely chronic. We used data from the National Ambulatory Medical Care Survey, 2007-2015, identifying visits with a new chronic musculoskeletal pain condition using pre-determined ICD-9 codes. We documented prescribing of non-opioid pain medication, opioids, physical therapy (PT), counseling, and other nonpharmacologic treatments and explored associations between patient and provider factors for each of these treatments. There were 111,994 visits over the 9-year period for a new case of chronic musculoskeletal pain, representing an average of 36.8 million weighted visits per year or approximately 11.8% of the population. Proportions that were prescribed nonopioid medication, opioids, PT, counseling and other nonpharmacologic treatments were: 40.2, 21.5, 10.0, 15.2 and 14.3 respectively. Patient age was associated with type of treatment with a young to old gradient for other nonpharmacologic treatments, PT, opioids, counseling and other medications. Orthopedists were less likely to prescribe pharmacological treatments than family practice physicians and more likely to prescribe PT. Physicians who used the electronic medical record were more likely to prescribe opioids. Contrary to practice guidelines for managing musculoskeletal pain, many patients are prescribed opioids for a new chronic musculoskeletal problem. PERSPECTIVE: We outlined in a representative sample of Americans what treatments are being prescribed for new cases of likely chronic musculoskeletal pain. Opioid prescription was double that of physical therapy. Using the electronic medical record was associated with more opioid prescription- a novel finding that should be corroborated by future research.

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Validation of CARE Scale-7 in treatment-seeking patients with chronic pain: measurement of sex invariance.

Social and interpersonal factors impact the trajectory of chronic pain. We previously developed and validated a 2-factor, 7-item measure to assess interpersonal factors, including relationship guilt and worry and difficulty prioritizing self-care in chronic pain. Here, we confirm the factor structure and examine the sex invariance of the two-factor structure of the CARE Scale-7.

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Association of chronic spinal pain with diet quality.

Chronic spinal pain is disabling and has high personal and societal costs. Risk factors include behavioral factors; however, little is known about the role of diet quality and its association with spinal pain. Higher diet quality and consumption of macronutrients that drive higher diet quality were hypothesized to be associated with lower odds of having spinal pain.

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Chronic Postoperative Pain After Hysterectomy for Endometrial Cancer: A Metabolic Profiling Study.

One out of seven women will develop a state of chronic postoperative pain following robot-assisted hysterectomy for endometrial cancer. Recently, metabolic studies have indicated that circulating lipids and lipoproteins could act as nociceptive modulators and thereby influence the induction and perpetuation of pain. The objectives of this explorative study were (1) to examine the preoperative serologic variations in concentrations of lipids, lipoproteins, and various low-molecular metabolites in patients with and without chronic postoperative pain after robot-assisted hysterectomy and (2) to explore if any of these serological biomarkers were predictive for development of chronic postoperative pain.

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