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Fluorescent probes have been used as effective methods for profiling proteins in biological system because of their high selectivity, sensitivity and temporal-spatial resolution. A specific fluorescent probe for understanding the function of the transient receptor potential ankyrin 1 (TRPA1) channel that is closely related with various diseases like persistent pain, respiratory and chronic itch syndromes, however, is still lacking. Here, we report a "turn-on" fluorescent probe (A1CA) for visualizing TRPA1 channels in the plasma membrane of live cells based on a photochromic ligand derived from 4-(phenylazo)benzenamine. Evaluating of the specificity and sensitivity of A1CA by electrophysiology and confocal imaging showed that A1CA probe displays higher affinity and selectivity to TRPA1 channel versus all other ion channels including TRPV1, TRPV3, Nav1.4, Nav1.5 and hERG. Based on the supporting evidence, A1CA has great potential as a molecular imaging probe for high-throughput screening of novel TRPA1 agonists.
Learn More >Accumulating evidence suggests that epigenetic mechanisms may hold great potential in the field of pain. We systematically reviewed the literature exploring epigenetic mechanisms in people with pain. Four databases have been interrogated: MEDLINE, The Cochrane Central Register of Controlled Trial, Scopus, and Web of Science, following PRISMA guidelines in conducting study selection and assessment. Thirty-seven studies were included. Studies explored epigenetics in conditions such as fibromyalgia, CRPS, neuropathies, or osteoarthritis. Research focussed on genome-wide and gene-specific DNA methylation, and miRNA expression. Bioinformatics analyses exploring miRNA-associated molecular pathways were also performed. Several genes already known for their role in pain (BDNF, HDAC4, PRKG1, IL-17, TNFRSF13B, etc.), and several miRNAs linked to inflammatory regulation, nociceptive signalling and protein kinases functions have been found to differ significantly between people with chronic pain and healthy controls. Although the studies included were cross-sectional in nature, and no conclusion on causal links between epigenetic changes and pain could be drawn, we summarised the large amount of data available in literature on the topic, highlighting results that have been replicated by independent investigations. The field of pain epigenetics appears very exciting and has all the potential to lead to remarkable scientific advances. However, high-quality, well-powered, longitudinal studies are warranted. Perspective: Though more high-quality research is needed, available research exploring epigenetic mechanisms or miRNAs in people with pain shows that genes regulating synaptic plasticity and excitability, protein kinases, and elements of the immune system might hold great potential in understanding the pathophysiology of different conditions.
Learn More >Inadequate pain management remains a problem in the emergency department (ED) and might increase the risk of chronic pain. Previous studies suggested that pain intensity is associated with pain chronification in specific patient groups. This study aims to study the association between pain intensity {[verbal] numeric rating scale ([V]NRS) ≥ 7} at discharge from the ED and pain chronification in the general population.
Learn More >Persistent pain (PP) and long-term conditions are all associated with psychological well-being. Less is known about their associations with reduced psychological well-being when co-occurring. We investigated how PP and long-term physical and mental conditions relate to psychological well-being when occurring together.
Learn More >Chronic pain due to osteoarthritis (OA) is a prevalent cause of global disability. New biomarkers are needed to improve treatment allocation, and genetic polymorphisms are promising candidates.
Learn More >The concept that a regional musculoskeletal pain may occur in the absence of identifiable tissue abnormality may be puzzling. Previously these regional complaints were generally categorized as myofascial pain syndromes, or prior to the formalization of the nociplastic pain concept, as musculoskeletal pain with a neuropathic component, and treatments were anatomically focussed. Chronic primary musculoskeletal pain is now identified under the chronic primary pain stem category with the mechanistic descriptor of nociplastic pain. It is possible that many patients previously diagnosed with myofascial pain do in fact suffer from chronic primary musculoskeletal pain, requiring a paradigm shift in management towards more centrally directed treatment strategies. Many questions remain, including validation of the proposed examination techniques, prevalence, ideal treatment, and uptake and acceptance by the healthcare community. This new classification should be welcomed as an explanation for regional pain conditions that previously responded poorly to physically focussed treatments.
Learn More >Fibromyalgia is a syndrome characterized by chronic widespread pain, with a multifactorial etiopathogenesis and high incidence of neuropsychiatric comorbidity. It has been inaccurately considered a pathological condition affecting only middle-aged women. The study aimed to explore the association of sociodemographic and clinical factors in patients with fibromyalgia with depression and/or anxiety. The present study is an analysis of a cross-sectional study of a secondary source. The prevalence ratio (PR) between the demographic and clinical variables of patients with fibromyalgia and concomitant depression and/or anxiety was calculated. Overall, 1,106 medical records were obtained with a confirmed diagnosis of fibromyalgia between 2010 and 2016; of these, 318 (28.75%) patients had an associated diagnosis of depression and/or anxiety. Approximately 28% women (295 of 1,052) and 42.6% men (23 of 54) suffered from depression and/or anxiety. In the adjusted explanatory model of depression and/or anxiety in patients with fibromyalgia, the relationship between sex (female PR = 0.5 [0.28-0.86]) and low socioeconomic strata (PR = 0.53 [0.33-0.70]) remained constant. In the study population, patients with fibromyalgia belonging to lower social strata were less likely to present with depression and anxiety. The male sex may pose as a risk factor for depression and/or anxiety in patients with fibromyalgia. Fibromyalgia has a huge impact on men's physical as well as mental health.
Learn More >Medication iatrogeny is a major public health problem that increases as the population ages. Therapeutic escalation to control pain and associated disorders could increase polypharmacy and iatrogeny. This study aimed to characterize the medication iatrogenic risk of elderly outpatients with chronic pain.
Learn More >For many medical conditions, clinicians can collect quantitative indicators of disease, such as heart rate, body temperature, or levels of a specific protein in a blood sample. For chronic pain, however, such biological markers have not yet been identified. This information gap occurs even though chronic pain is one of the most common reasons why adults seek medical care [1]. If they could be identified, biological markers (or "biomarkers") for chronic pain could improve patient care by giving doctors a more complete picture of a particular patient's condition.
Learn More >For centuries, cannabis and its components have been used to manage a wide variety of symptoms associated with many illnesses. Gastrointestinal (GI) diseases are no exception in this regard. Individuals suffering from inflammatory bowel disease (IBD) are among those who have sought out the ameliorating properties of this plant. As legal limitations of its use have eased, interest has grown from both patients and their providers regarding the potential of cannabis to be used in the clinical setting. Similarly, a growing number of animal and human studies have been undertaken to evaluate the impact of cannabis and cannabinoid signaling elements on the natural history of IBD and its associated complications. There is little clinical evidence supporting the ability of cannabis or related products to treat the GI inflammation underlying these disorders. However, 1 recurring theme from both animal and human studies is that these agents have a significant impact on several IBD-related symptoms, including abdominal pain. In this review, we discuss the role of cannabis and cannabinoid signaling in visceral pain perception, what is currently known regarding the efficacy of cannabis and its derivatives for managing pain, related symptoms and inflammation in IBD, and what work remains to effectively utilize cannabis and its derivatives in the clinical setting.
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