Browse by Audience
Atopic dermatitis (AD) is a chronic inflammatory skin disease that greatly impacts patient quality of life. Type 2 cytokine interleukin (IL)-13 is integral to the pathogenesis of AD. Tralokinumab is a fully human IgG4 monoclonal antibody that specifically targets IL-13, preventing downstream signaling of inflammatory pathways that may contribute to AD. Tralokinumab was US Food and Drug administration (FDA) recently approved for the treatment of moderate to severe AD on December 28, 2021. In our review, we will explore the efficacy and adverse effects (AEs) of tralokinumab for the treatment of patients with moderate to severe AD. A PubMed search for key articles on the emerging clinical data of tralokinumab was performed. Six randomized controlled trials of tralokinumab identified improvements in disease severity measures, including Investigator's Global Assessment (IGA) scores and Eczema Area Severity Index 75 (EASI75) scores. Four of these studies demonstrated improvements in quality of life measures with tralokinumab, including pruritus scores, sleep interference scores, Dermatology Life Quality Index, SCORing Atopic Dermatitis (SCORAD), Patient Oriented Eczema Measure, and The Short Form 36 Health Survey (SF-36v2) scores. One study identified a similar immune response in patients taking tralokinumab to those taking the Tdap and meningococcal vaccines. Upper respiratory infection, conjunctivitis, and headaches were the most common adverse events. The varying criteria to assess changes in AD disease severity across different studies is a limitation of this review. Tralokinumab is another promising biologic option for the treatment of moderate to severe AD, which may reduce disease burden and improve patient quality of life.
Learn More >The research and clinical application of the noninvasive brain stimulation (NIBS) technique in the treatment of neuropathic pain (NP) are increasing. In this review article, we outline the effectiveness and limitations of the NIBS approach in treating common central neuropathic pain (CNP). This article summarizes the research progress of NIBS in the treatment of different CNPs and describes the effects and mechanisms of these methods on different CNPs. Repetitive transcranial magnetic stimulation (rTMS) analgesic research has been relatively mature and applied to a variety of CNP treatments. But the optimal stimulation targets, stimulation intensity, and stimulation time of transcranial direct current stimulation (tDCS) for each type of CNP are still difficult to identify. The analgesic mechanism of rTMS is similar to that of tDCS, both of which change cortical excitability and synaptic plasticity, regulate the release of related neurotransmitters and affect the structural and functional connections of brain regions associated with pain processing and regulation. Some deficiencies are found in current NIBS relevant studies, such as small sample size, difficulty to avoid placebo effect, and insufficient research on analgesia mechanism. Future research should gradually carry out large-scale, multicenter studies to test the stability and reliability of the analgesic effects of NIBS.
Learn More >The purpose of this study was to investigate pain and radiological features of different types of first-episode demyelinating optic neuritis (ON).
Learn More >To investigate the effectiveness of sufentanil patient-controlled intravenous analgesia pump (PCIA) and background infusion in patients of post-cesarean analgesia.
Learn More >To analyze the effect and mechanism of dexmedetomidine (DEX) analgesia pretreatment on functional chronic visceral pain in rats.
Learn More >Paclitaxel is widely used as a first-line chemotherapy agent to treat malignant tumors. However, paclitaxel causes peripheral nerve fiber damage and neuropathic pain in some patients. In addition, patients received paclitaxel chemotherapy are often accompanied by negative emotions such as anxiety. The amygdala is critically involved in regulating pain signals, as well as anxiety. The purpose of this study is to clarify the role of Ca/calmodulin-dependent protein kinase II (CaMKII)-positive glutamatergic neurons in the amygdala in paclitaxel-induced pain and negative affective symptoms. Intraperitoneal injection of paclitaxel into mice caused mechanical and thermal allodynia, as measured by Von Frey test and Hargreaves test, and anxiety, as measured by open field test and elevated plus maze test. Immunofluorescence staining revealed that c-fos-positive neurons were significantly more in the basolateral amygdala (BLA) and central amygdala (CeA) in paclitaxel-treated mice than untreated mice. Furthermore, part of c-fos-positive neurons in the BLA were immunoreactive of CaMKII. Engineered Designer receptors exclusively activated by designer drugs (DREADD) receptor hM4Di or hM3Dq was selectively expressed on CaMKII neurons by injection of adeno-associated virus (AAV) vectors containing CaMKII and hM4Di or hM3Dq. Administration of DREADD agonist CNO to selectively inhibit the CaMKII neurons in the BLA significantly increased the paw withdrawal thresholds and paw withdrawal latencies. In addition, selectively inhibition of CaMKII neurons in the BLA alleviated anxiety behavior without affecting the motor activity. In summary, our findings suggest that CaMKII neurons in the amygdala are critical for neuropathic pain and anxiety behaviors induced by paclitaxel chemotherapy.
Learn More >Opioids remain an essential part of the treatment of chronic pain. However, their use and increasing rates of misuse are associated with high morbidity and mortality. The development of tolerance to opioids and analgesics further complicates dosing and the need to reduce side effects. First-generation digital systems were developed to improve analgesics but are not always capable of making clinically relevant associations and do not necessarily lead to better clinical efficacy. A lack of improved clinical outcomes makes these systems less applicable for adoption by clinicians and patients. There is a need to enhance the therapeutic regimens of opioids. In the present paper, we present the use of a digital analgesic that consists of an analgesic administered under the control of a second-generation artificial intelligence system. Second-generation systems focus on improved patient outcomes measured based on clinical response and reduced side effects in a single subject. The algorithm regulates the administration of analgesics in a personalized manner. The digital analgesic provides advantages for both users and providers. The system enables dose optimization, improving effectiveness, and minimizing side effects while increasing adherence to beneficial therapeutic regimens. The algorithm improves the clinicians' experience and assists them in managing chronic pain. The system reduces the financial burden on healthcare providers by lowering opioid-related morbidity and provides a market disruptor for pharma companies.
Learn More >Nociception refers to the process of encoding and processing noxious stimuli, which allow animals to detect and avoid potentially harmful stimuli. Several types of stimuli can trigger nociceptive sensory transduction, including thermal, noxious chemicals, and harsh mechanical stimulation that depend on the corresponding nociceptors. In view of the high evolutionary conservation of the mechanisms that govern nociception from to mammals, investigation in the fruit fly help us understand how the sensory nervous system works and what happen in nociception. Here, we present an overview of currently identified conserved genetics of nociception, the nociceptive sensory neurons responsible for detecting noxious stimuli, and various assays for evaluating different nociception. Finally, we cover development of anti-pain drug using fly model. These comparisons illustrate the value of using as model for uncovering nociception mechanisms, which are essential for identifying new treatment goals and developing novel analgesics that are applicable to human health.
Learn More >Paracetamol, or acetaminophen (AAP), is the most commonly used analgesic during pregnancy and early life. While therapeutic doses of AAP are considered harmless during these periods, recent findings in both humans and rodents suggest a link between developmental exposure to AAP and behavioral consequences later in life. The aim of this study is to evaluate the impact of neonatal exposure to clinically relevant doses of AAP on adult spontaneous behavior, habituation, memory, learning, and cognitive flexibility later in life using a mouse model. Markers of oxidative stress, axon outgrowth, and glutamatergic transmission were also investigated in the hippocampus during the first 24 h after exposure. In addition, potential long-term effects on synaptic density in the hippocampus have been investigated. In a home cage setting, mice neonatally exposed to AAP (30 + 30 mg/kg, 4 h apart) on postnatal day 10 displayed altered spontaneous behavior and changed habituation patterns later in life compared to controls. These mice also displayed reduced memory, learning and cognitive flexibility compared to control animals in the Morris water maze. An increase of markers for oxidative stress was observed in the hippocampus 6 h after AAP exposure. As AAP is the first choice treatment for pain and/or fever during pregnancy and early life, these results may be of great importance for risk assessment. Here we show that AAP can have persistent negative effects on brain development and suggest that AAP, despite the relatively low doses, is capable to induce acute oxidative stress in the hippocampus.
Learn More >Psoriatic arthritis (PsA) is a form of chronic inflammatory arthritis associated with psoriasis and a multitude of other symptoms, most commonly arthritis, dactylitis, enthesitis and axial involvement. PsA is significantly heterogeneous, with a highly variable clinical course of PsA. Patients may experience significant or mild skin and joint symptoms, with some patients developing rapidly progressing joint destruction and skin symptoms. Despite the range of symptom severity, PsA is frequently associated with significantly impaired quality of life from joint destruction, as well as chronic pain and a range of comorbidities such as depression and cardiovascular disease. Currently, there are no definitive diagnostic tests for PsA, with diagnosis remaining challenging owing to the heterogeneous presentation and course of the disease. Presently, the CASPAR criteria are often used to aid rheumatologists in distinguishing PsA from other inflammatory arthritides. Treatment options for patients have been expanded over the last two decades with the emerging clinical utility of biological therapies. However, early identification and diagnosis of patients and effective disease control remain unmet medical needs within the PsA community. In addition, predicting response to treatment also remains a challenge to rheumatologists. This review highlights the current hurdles faced by healthcare professionals in the diagnosis and management of PsA patients and provides future action points for consideration by the members of the multidisciplinary team who treat PsA patients.
Learn More >