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Chronic pain (CP) is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage lasting longer than 3 months. CP is the main reason why people seek medical care and exerts an enormous economic burden. Genome-wide expression analysis has revealed that diverse essential genetic elements are altered in CP patients. Although many possible mechanisms of CP have been revealed, we are still unable to meet all the analgesic needs of patients. In recent years, non-coding RNAs (ncRNAs) have been shown to play essential roles in peripheral neuropathy and axon regeneration, which is associated with CP occurrence and development. Multiple key ncRNAs have been identified in animal models of CP, such as microRNA-30c-5p, ciRS-7, and lncRNA MRAK009713. This review highlights different kinds of ncRNAs in the regulation of CP, which provides a more comprehensive understanding of the pathogenesis of the disease. It mainly focuses on the contributions of miRNAs, circRNAs, and lncRNAs to CP, specifically peripheral neuropathic pain (NP), diabetic NP, central NP associated with spinal cord injury, complex regional pain syndrome, inflammatory pain, and cancer-induced pain. In addition, we summarize some potential ncRNAs as novel biomarkers for CP and its complications. With an in-depth understanding of the mechanism of CP, ncRNAs may provide novel insight into CP and could become new therapeutic targets in the future.

The opioid crisis brought scrutiny to opioid prescribing. Understanding how opioid prescribing patterns and corresponding patient outcomes changed during the epidemic is essential for future targeted policies. Many studies attempt to model trends in opioid prescriptions therefore understanding the temporal shift in opioid prescribing patterns across populations is necessary. This study characterized postoperative opioid prescribing patterns across different populations, 2010-2020.

Chronic, abdominal pain remains a problem in a subset of patients after cholecystectomy. The cause is often obscure but central sensitization may be an important component and could theoretically be mediated by spinal PGE2, which is regulated by several cytokines. The aim of the study was to examine cerebrospinal fluid (CSF) of participants with post cholecystectomy syndrome and healthy volunteers for signs of PGE2 and cytokine mediated central sensitization.

Sickle cell disease is an autosomal recessive disorder characterized by the presence of sickle hemoglobin that leads to chronic hemolysis and vaso-occlusive crisis. After decades of limited therapy options, crizanlizumab is a humanized monoclonal antibody approved by the Food and Drug Administration (FDA) in 2019 for sickle cell-related pain crises for patients 16 years of age and above. Although rare, infusion-related reactions, including painful crises, occurred in 3% as per the package insert. However, the data on how to deal with such reactions and about further treatment outcomes are limited as most patients stopped crizanlizumab after the reaction. Herein, we report the good outcome of 13 doses of crizanlizumab in a 19-year-old female patient with sickle cell disease on hydroxyurea, despite experiencing a severe infusion-related painful crisis during the second infusion. Additional benefits of crizanlizumab, in this case, were preventing new episodes of acute chest syndrome, quitting chronic narcotics use, and a remarkable improvement in quality of life and overall performance.

Acute lung injury (ALI) is a severe clinical disorder characterized by dysregulated inflammatory responses, leading to high rates of morbidity and mortality. Cinobufagin, a primary component isolated from cinobufotalin, exerts strong anticancer effects. However, there are few reports on its role in ALI, and it is unclear whether cinobufagin affects lipopolysaccharide (LPS)-induced ALI. Therefore, the present study aimed to investigate the effect of cinobufagin on LPS-induced ALI and to assess its potential mechanism of action. The results showed that cinobufagin alleviated lung histopathological changes and protected the permeability of lung tissues in LPS-induced ALI. In addition, cinobufagin effectively suppressed inflammatory responses through the induction of autophagy in LPS-induced ALI cells and in a mouse model. Moreover, cinobufagin enhanced autophagy through the p53/mTOR pathway in LPS-induced ALI. Herein, it was reported for the first time that cinobufagin inhibited the inflammatory response of LPS-induced ALI, which laid the foundation for further understanding and development of cinobufagin as a potential new drug for ALI.

Patients with Gaucher disease (GD) have progressive bone involvement that clinically presents with debilitating bone pain, structural bone changes, bone marrow infiltration (BMI), Erlenmeyer (EM) flask deformity, and osteoporosis. Pain is referred by the majority of GD patients and continues to persist despite the type of therapy. The pain in GD is described as chronic deep penetrating pain; however, sometimes, patients experience severe acute pain. The source of bone pain is mainly debated as nociceptive pain secondary to bone pathology or neuropathic or inflammatory origins. Osteocytes constitute a significant source of secreted molecules that coordinate bone remodeling. Osteocyte markers, sclerostin (SOST) and Dickkopf-1 (DKK-1), inactivate the canonical Wnt signaling pathway and lead to the inhibition of bone formation. Thus, circulated sclerostin and DKK-1 are potential biomarkers of skeletal abnormalities. This study aimed to assess the circulating levels of sclerostin and DKK-1 in patients with GD and their correlation with clinical bone pathology parameters: pain, bone mineral density (BMD), and EM deformity. Thirty-nine patients with GD were classified into cohorts based on the presence and severity of bone manifestations. The serum levels of sclerostin and DKK-1 were quantified by enzyme-linked immunosorbent assays. The highest level of sclerostin was measured in GD patients with pain, BMI, and EM deformity. The multiparameter analysis demonstrated that 95% of GD patients with pain, BMI, and EM deformity had increased levels of sclerostin. The majority of patients with elevated sclerostin also have osteopenia or osteoporosis. Moreover, circulating sclerostin level increase with age, and GD patients have elevated sclerostin levels when compared with healthy control from the same age group. Pearson's linear correlation analysis showed a positive correlation between serum DKK-1 and sclerostin in healthy controls and GD patients with normal bone mineral density. However, the balance between sclerostin and DKK-1 waned in GD patients with osteopenia or osteoporosis. In conclusion, the osteocyte marker, sclerostin, when elevated, is associated with bone pain, BMI, and EM flask deformity in GD patients. The altered sclerostin/DKK-1 ratio correlates with the reduction of bone mineral density. These data confirm that the Wnt signaling pathway plays a role in GD-associated bone disease. Sclerostin and bone pain could be used as biomarkers to assess patients with a high risk of BMI and EM flask deformities.

Peripheral nerve injury leads to severe neuropathic pain. Previous studies have highlighted the beneficial effects of physical exercise on alleviating neuropathic pain. Exercise regulating transforming growth factor-1 (TGF-1) can improve several diseases and relieve neuropathic pain induced by peripheral nerve injury. Here, we investigated whether exercise could alleviate neuropathic pain by modulating TGF-1 expression. We assessed mechanical and cold pain behavior and conducted molecular evaluation of the spinal cord. We found that spared nerve injury (SNI) led to mechanical and cold allodynia in the hind paw, elevated the expression of latency-associated peptide- (LAP-) TGF-1, and activated astroglial in the spinal cord. Exercise decreases allodynia, astroglial activation, and LAP-TGF-1 in SNI mice. Intrathecal injection of a TGF-type I receptor inhibitor attenuated exercise analgesia and enhanced astroglial activation. These findings demonstrate that exercise induces analgesia by promoting TGF-1 activation and inhibiting astrogliosis. Our study reveals a new underlying mechanism for exercise-attenuated neuropathic pain in the maintenance stage of neuropathic pain after nerve injury.

Gut microbiota alterations are strongly associated with prescription opioid use (POU) and multisite chronic pain (MCP). However, whether or not these associations are causal remains unknown. Therefore, we aim to explore the causal relationships between them comprehensively.

Paracoccidioidomycosis is a systemic infection caused by the fungus Paracoccidioides. It may present in two forms: an acute/subacute form, whose most frequent manifestations include weight loss, fever, anemia, and adenopathy, and a chronic condition with mainly respiratory symptoms. Digestive symptoms, although they may occur, are not frequently reported. Paracoccidioidomycosis usually affects adult male agricultural workers; thus, its presentation in children is rare.

Multisystem inflammatory syndrome in children (MIS-C) is a rare but serious condition that can potentially develop after SARS-CoV-2 infection in children. Gastrointestinal manifestation in MIS-C can mimic acute abdomen, potentially leading to unnecessary surgical treatment. Immune-mediated mechanisms seem to be a determining factor in its pathogenesis, and histological studies can help to shed light on this aspect. We describe three cases of children diagnosed with MIS-C that underwent appendectomy.