Rejected

Nociceptive transmission at the spinal cord is modulated by descending pain inhibitory systems originating in the brainstem that interact with neural cardiovascular pathways, such as baroreceptor input. However, data regarding antinociceptive properties of cardiopulmonary baroreceptors are largely mixed, and no studies have examined cardiopulmonary baroreceptor modulation of pain perception in patients with chronic pain. Therefore, we tested the hypothesis that cardiopulmonary baroreceptor unloading would reduce pain perception in chronic back pain (CBP) patients and healthy participants. Mechanical pressure pain threshold (algometer on the upper trapezius) and pain perception of a repetitive heat stimulus (thermode on the anterior forearm) was tested in 12 CBP patients and 8 healthy controls during supine lower body negative pressure (LBNP) of -10 mmHg and 0 mmHg (control condition). Pressure pain threshold during LBNP was significantly increased compared with the control condition in CBP patients (270 ± 31 vs. 240 ± 27 kPa, P=0.04) and healthy controls (293 ± 59 vs. 259 ± 50 kPa, P=0.02), indicating reduced pain perception. Similarly, the average pain rating (scale 0-100) of the repetitive heat stimulus was significantly reduced during LBNP compared with the control condition in CBP patients (42 ± 6 vs. 48 ± 6, P<0.01). However, no significant change was observed in average pain rating of the repetitive heat stimulus during LBNP in healthy controls (38 ± 5 vs. 37 ± 7, P=0.89). Together, these preliminary findings suggest reduced pain perception during cardiopulmonary baroreceptor unloading with a potentially greater effect in patients with CBP compared with healthy individuals.

Migraine is a common brain disorder characterized by recurrent episodes of headache. It is a complex and multifactorial disease with a higher prevalence in females than in males. Several risk factors have been associated to migraine disease as genetic factors, sex and age. The pathophysiology of migraine is still unclear; however, it has been proven that NOD-like receptor protein 3 (NLRP3) inflammasome pathway overactivation as well as p-ERK/p-CREB axis contribute to migraine pathogenesis. Therefore, the aim of this study was to investigate the effect of BAY-117082, a NLRP3 inflammasome inhibitor and p-ERK/p-CREB modulator, in an in vivo model of nitroglycerin (NTG)-induced migraine. Migraine model was induced by NTG intraperitoneal administration at dose of 10 mg/kg diluted in 0.9% saline. Mice were treated intraperitoneally with BAY-117082 at doses of 1 mg/kg, 5 mg/kg, and 10 mg/kg, 5 minutes after NTG injection. Mice were sacrificed 4 h following NTG injection; the whole brain with the rostral spinal cord was removed to perform several analysis. Our results demonstrated that, following behavioral tests for pain and photophobia, BAY-117082 treatment at doses of 5 mg/kg and 10 mg/kg reduced pain attacks induced by NTG more than BAY-117082 at the dose of 1 mg/kg. Moreover, the treatment with BAY-117082 at doses of 5 mg/kg and 10 mg/kg significantly reduced histological damage in the trigeminal nerve nucleus and significantly decreased inflammosome activation by reduction of NLRP3, ASC, IL-1β and TNF-α expression. Additionally, the treatment with BAY-117082 at doses of 5 mg/kg and 10 mg/kg significantly modulated p-ERK/p-CREB axis activation through the reduction of p-ERK, p-AKT, p-CREB and p-PI3K expression. Therefore, the obtained results offer new insight into the role of NLRP3 inflammasome pathway and p-ERK/p-CREB axis in migraine pathogenesis, suggesting that BAY-117082 could be considered a novel therapeutic strategy to treat migraine.

Post-acute sequelae of COVID-19, commonly known as long-COVID, is defined as a persistent symptom(s) that is unexplainable by alternative diagnosis and lasts beyond three months after the onset of COVID-19. Several studies have now identified long-COVID in >50% of COVID-19 patients, emphasizing the need for elucidating mechanisms underlying these symptoms. Pain is a prevalent symptom in long-COVID patients and presents as headache, persistent muscle pain, joint pain, stomach pain, chest pain, respiratory discomfort, and dysesthesia or paresthesia. Understanding the molecular underpinnings of pain maintenance in these patients could provide information on novel therapeutic strategies. Our lab has previously identified novel treatments for pain due to peripheral inflammation from dysesthesia-inducing mechanisms associated with acute SARS-CoV-2 (SCV2) respiratory infection in hamsters (1-4 days post-infection, dpi). We have also previously demonstrated the validity of long-term infection of hamsters (30-60 dpi) as a pre-clinical model of long-COVID. By utilizing the Von Frey assay, we found that SCV2, but not Influenza A, causes mechanical hypersensitivity at 28 dpi in both male and female hamsters. Bulk RNA sequencing of 31 dpi thoracic dorsal root ganglia (DRGs) revealed a unique transcriptional perturbation signature (168 DEGs, 47 up & 121 down, p-adj.<0.1), despite viral clearance at approximately 7 dpi. Ingenuity Pathway Analysis of this sequencing (853 DEGs, p-nom.<0.05) identified several injury-related canonical pathways, including Production of NO & ROS in Macrophages, Signaling by Rho Family GTPases, mTOR Signaling, Estrogen Receptor Signaling, and Ephrin Receptor Signaling. The Enrichr DisGeNET browser associated these transcriptional changes with clinical neurodegeneration phenotypes, including Amyotrophic Lateral Sclerosis, Alzheimer's Disease, Neurodegenerative Disorders, and Parkinson Disease. Of note, TUNEL staining did not demonstrate any sign of SCV2-induced sensory neuron apoptosis at 31 dpi. Further investigation of the sequencing dataset revealed a broad downregulation of TubbmRNA isoforms and Mbp, suggesting microtubule and myelin dysregulation. We also observed a drastic increase in Scn8areads, which could point to Na 1.6-induced DRG neuron hyperexcitability. In conclusion, our findings suggest that SCV2 leaves a lasting hypersensitivity-associated transcriptomic signature in DRGs despite early viral clearance that appears to be associated with neurodegeneration mechanisms. As we continue investigating the mechanisms underlying SCV2-induced actions in DRGs and peripheral nerves, we will also use an upstream regulator analysis of our RNA sequencing data to identify promising therapeutic targets.

Emergence of severe acute respiratory syndrome coronavirus 2 infections and the resultant disease, COVID-19 led the world into 238 million cases and 4.8 million deaths over the first 22 months of the pandemic. While numerous vaccines have been developed to combat this pandemic, limited literature is available regarding the comparison of these vaccines. This study aims to systematically review and evaluate the immunogenicity and safety of COVID-19 vaccines compared with control arms in the healthy adult population.

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory condition that may involve multiple organ systems. Although the antinuclear antibody (ANA) test is positive in nearly every case of SLE, it is not specific for this disease and must be interpreted in the appropriate clinical context. Key features that warrant ANA testing include unexplained multisystem inflammatory disease, symmetric joint pain with inflammatory features, photosensitive rash, and cytopenias. ANA staining patterns and more specific autoantibody testing may be helpful in diagnosis of suspected SLE or ANA-associated disease. For patients with nonspecific symptoms, such as malaise and fatigue, ANA testing is of limited value.

Vestibular migraine (VM) remains an underdiagnosed condition, often mistaken with brainstem aura. VM is defined by recurrent vestibular symptoms in at least 50% of migraine attacks. Diagnosis is established by clinical criteria based on the International Classification of Headache Disorders (ICHD-3). Estimated prevalence of VM is 1 to 2.7% of the adult population. Vestibular symptoms usually appear after the headache. VM pathophysiology remains poorly understood. Vertigo may occur before, during, after the migraine attack, or even independently, and may last seconds to hours or days. Pathophysiological mechanisms for VM are still poorly understood and are usually extrapolated from migraines. Differential diagnoses include Ménière's disease, benign paroxysmal positional vertigo, brainstem aura, transient ischemic attack, persistent perceptual postural vertigo, and episodic type 2 ataxia. Specific treatment recommendations for vestibular migraine are still scarce.

Amidst the coronavirus disease 2019 (COVID-19) pandemic, the use of personal protective equipment (PPE) is mandatory for healthcare workers to remain protected against infection. The present study was undertaken to evaluate challenges faced by the healthcare workers while using level 3 PPE.

Prevention of the start of the neural cascade may result in long-term advantages by the elimination of hypersensitivity produced by noxious stimulus. This study was designed to evaluate postoperative pain and long-term functional outcomes after pre-emptive ultrasound (US)-guided caudal analgesia in patients undergoing spinal laminectomy.

Epipericardial or epicardial fat necrosis (EFN) is a self-limited inflammatory process occurring in the mediastinal fat surrounding the heart. It is an uncommon cause of acute chest pain and mimics more critical clinical disorders such as acute coronary syndrome, aortic dissection, and pulmonary embolism. However, EFN is frequently overlooked and under-recognized in emergency departments (EDs) owing to the unfamiliarity of this condition among physicians and radiologists. Herein, we present the case of a previously healthy young male patient, with a recent history of mild COVID-19 infection (two weeks before presentation), who presented to the ED for acute chest pain. Paraclinical evaluation including computed tomography (CT) of the chest revealed fat stranding along with the left epicardial fat pad in favor of EFN.

Among the multiple causes of low back and lower extremity pain, sacroiliac joint pain has shown to be prevalent in 10% to 25% of patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis. Over the years, multiple Current Procedural Terminology (CPT) codes have evolved with the inclusion of intraarticular injections, nerve blocks, and radiofrequency neurotomy, in addition to percutaneous sacroiliac joint fusions. Previous assessments of utilization patterns of sacroiliac joint interventions only included sacroiliac joint intraarticular injections, since the data was not available prior to the introduction of new codes. A recent assessment revealed an increase of 11.3%, and an annual increase of 1.2% per 100,000 Medicare population from 2009 to 2018, showing a decline in growth patterns. During the past 2 years, the COVID-19 pandemic has also had significant effects on the utilization patterns of sacroiliac joint interventions.