Rejected

Computational modeling of the neural activity in the human spinal cord may help elucidate the underlying mechanisms involved in the complex processing of painful stimuli. In this study, we use a biologically-plausible model of the dorsal horn circuitry as a platform to simulate pain processing under healthy and pathological conditions. Specifically, we distort signals in the receptor fibers akin to what is observed in axonal damage and monitor the corresponding changes in five quantitative markers associated with the pain response. Axonal damage may lead to spike-train delays, evoked potentials, an increase in the refractoriness of the system, and intermittent blockage of spikes. We demonstrate how such effects applied to mechanoreceptor and nociceptor fibers in the pain processing circuit can give rise to dramatically distinct responses at the network/population level. The computational modeling of damaged neuronal assemblies may help unravel the myriad of responses observed in painful neuropathies and improve diagnostics and treatment protocols.

COVID-19 is a severe respiratory disease caused by the newly identified human coronavirus (HCoV) Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The virus was discovered in December 2019, and in March 2020, the disease was declared a global pandemic by the World Health Organization (WHO) due to a high number of cases. Although SARS-CoV-2 primarily affects the respiratory system, several studies have reported neurological complications in COVID-19 patients. Headache, dizziness, loss of taste and smell, encephalitis, encephalopathy, and cerebrovascular diseases are the most common neurological complications that are associated with COVID-19. In addition, seizures, neuromuscular junctions' disorders, and Guillain-Barré syndrome were reported as complications of COVID-19, as well as neurodegenerative and demyelinating disorders. However, the management of these conditions remains a challenge. In this review, we discuss the prevalence, pathogenesis, and mechanisms of these neurological sequelae that are secondary to SARS-CoV-2 infection. We aim to update neurologists and healthcare workers on the possible neurological complications associated with COVID-19 and the management of these disease conditions.

Epilepsy is a highly prevalent neurological condition characterised by repeated unprovoked seizures with various aetiologies. Although antiepileptic medications produce clinical improvement in many individuals, nearly a third of individuals have drug-resistant epilepsy that carries significant morbidity and mortality, and even individuals who have clinical improvement from antiepileptic medications often report iatrogenic symptoms. There remains a need for non-invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low-frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy. This is an updated version of the original Cochrane Review published in 2016.

One of the key strategies for effective pain management involves delaying analgesic tolerance. Early clinical reports indicate an extraordinary effectiveness of off-label disulfiram-an agent designed for alcohol use disorder-in potentiating opioid analgesia and abrogation of tolerance. Our study aimed to determine whether sustained µ-opioid signaling upon disulfiram exposure contributes to these phenomena. Wistar rats were exposed to acute and chronic disulfiram and morphine cotreatment. Nociceptive thresholds were assessed with the mechanical Randal-Selitto and thermal tail-flick tests. µ-opioid receptor activation in brain structures important for pain processing was carried out with the [S]GTPγS assay. The results suggest that disulfiram (12.5-50 mg/kg i.g.) augmented morphine antinociception and diminished morphine (25 mg/kg, i.g.) tolerance in a supraspinal, opioid-dependent manner. Disulfiram (25 mg/kg, i.g.) induced a transient enhancement of µ-opioid receptor activation in the periaqueductal gray matter (PAG), rostral ventromedial medulla (RVM), hypothalamus, prefrontal cortex and the dorsal striatum at day 1 of morphine treatment. Disulfiram rescued µ-opioid receptor signaling in the nucleus accumbens and caudate-putamen 14 days following morphine and disulfiram cotreatment. The results of this study suggest that striatal µ-opioid receptors may contribute to the abolition of morphine tolerance following concomitant treatment with disulfiram.

Although cardiovascular imaging techniques are widely used to diagnose myocardial ischemia in patients with suspected stable coronary artery disease (CAD), they have limitations related to lack of specificity, sensitivity and "late" diagnosis. Additionally, the absence of a simple laboratory test that can detect myocardial ischemia in CAD patients, has led to many patients being first diagnosed at the time of the development of myocardial infarction. Nourin is an early blood-based biomarker rapidly released within five minutes by "reversible" ischemic myocardium before progressing to necrosis. Recently, we demonstrated that the Nourin-dependent (marker of cell damage) and (marker of inflammation) can diagnose myocardial ischemia in patients with unstable angina (UA) and also stratify severity of ischemia, with higher expression in acute ST-segment elevation myocardial infarction (STEMI) patients compared to UA patients. Minimal baseline-gene expression levels of Nourin miRNAs were detected in healthy subjects.

Migraine is one of the most prevalent headache disorders in children and negatively influences their quality of life. Physical, social, and school functioning are negatively affected. Mood changes are common in migraineurs and may happen before, during, or after a migraine headache. Children with migraine are not exempt from mood swings. The majority of mood changes occur during the prodromal phase, manifesting as a psychobiological response, e.g., difficulty thinking, trouble concentrating, irritability, higher or lower energy, confusion, and depression. A bi-directional relationship between migraine and mood has been proposed, but mechanisms are not clear. Collectively, a maladaptive stress response has been suggested to explain the inability to balance homoeostatic changes when facing various stressors. Recognizing mood changes and monitoring mood patterns in children with migraine, for example, by various apps and so-called mood monitors, is valuable for better management. A multidisciplinary intervention has been recommended to reduce migraine disability, improve coping strategies, and reduce chronification risks in children with migraine. Pharmacological and non-pharmacological strategies are both available and effective. Biofeedback, relaxation, and cognitive-behavioral therapy yield positive outcomes in pediatric migraine. Developing healthy lifestyle habits (diet, exercise, sleep) also seems to improve migraine in this population.

Pain is managed using a biopsychosocial approach and pharmacological and non-pharmacological treatments. Transcutaneous electrical nerve stimulation (TENS) is a technique whereby pulsed electrical currents are administered through the intact surface of the skin with the intention of alleviating pain, akin to 'electrically rubbing pain away'. Despite over 50 years of published research, uncertainty about the clinical efficacy of TENS remains. The purpose of this comprehensive review is to critically appraise clinical research on TENS to inform future strategies to resolve the 'efficacy-impasse'. The principles and practices of TENS are described to provide context for readers unfamiliar with TENS treatment. The findings of systematic reviews evaluating TENS are described from a historical perspective to provide context for a critical evaluation of factors influencing the outcomes of randomized controlled trials (RCTs); including sample populations, outcome measures, TENS techniques, and comparator interventions. Three possibilities are offered to resolve the impasse. Firstly, to conduct large multi-centered RCTs using an enriched enrolment with randomized withdrawal design, that incorporates a 'run-in phase' to screen for potential TENS responders and to optimise TENS treatment according to individual need. Secondly, to meta-analyze published RCT data, irrespective of type of pain, to determine whether TENS reduces the intensity of pain during stimulation, and to include a detailed assessment of levels of certainty and precision. Thirdly, to concede that it may be impossible to determine efficacy due to insurmountable methodological, logistical and financial challenges. The consequences to clinicians, policy makers and funders of this third scenario are discussed. I argue that patients will continue to use TENS irrespective of the views of clinicians, policy makers, funders or guideline panel recommendations, because TENS is readily available without prescription; TENS generates a pleasant sensory experience that is similar to easing pain using warming and cooling techniques; and technological developments such as smart wearable TENS devices will improve usability in the future. Thus, research is needed on how best to integrate TENS into existing pain management strategies by analyzing data of TENS usage by expert-patients in real-world settings.

The purpose of this systematic review was to determine the analgesic efficacy and adverse effects of ibuprofen in comparison with other traditional non-opioid analgesics after third molar surgery. A total of 17 full texts were identified in PubMed and assessed using the Cochrane Collaboration's risk of bias tool by two independent researchers. The sum of pain intensity differences, total pain relief, the overall evaluation, the number of patients requiring rescue analgesics, and adverse effects were collected. Data were analyzed using the Review Manager Software 5.3. for Windows. A total of 15 articles met the criteria. The qualitative and quantitative analysis showed that ibuprofen is more effective to relieve post-operative dental pain than acetaminophen, meclofenamate, aceclofenac, bromfenac, and aspirin. Moreover, ibuprofen and traditional non-steroidal anti-inflammatory drugs have a similar safety profile. In conclusion, ibuprofen 400 mg appears to have good analgesic efficacy and a safety profile similar to other traditional non-steroidal anti-inflammatory drugs after third molar surgery.

At present, the clinical strategies for treating chronic wounds are limited, especially when it comes to pain relief and rapid wound healing. Therefore, there is an urgent need to develop alternative treatment methods. This paper provides a systematic review on recent researches on how electrospun nanofiber scaffolds promote wound healing and how the electrospinning technology has been used for fabricating multi-dimensional, multi-pore and multi-functional nanofiber scaffolds that have greatly promoted the development of wound healing dressings. First, we provide a review on the four stages of wound healing, which is followed by a discussion on the evolvement of the electrospinning technology, what is involved in electrospinning devices, and factors affecting the electrospinning process. Finally, we present the possible mechanisms of electrospun nanofibers to promote wound healing, the classification of electrospun polymers, cell infiltration favoring fiber scaffolds, antibacterial fiber scaffolds, and future multi-functional scaffolds. Although nanofiber scaffolds have made great progress as a type of multi-functional biomaterial, major challenges still remain for commercializing them in a way that fully meets the needs of patients.

Coronary risk scores (CRS) including History, Electrocardiogram, Age, Risk Factors, Troponin (HEART) score and Emergency Department Assessment of Chest pain Score (EDACS) can help identify patients at low risk of major adverse cardiac events. In the emergency department (ED), there are wide variations in hospital admission rates among patients with chest pain.