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“Visualization” of pain using cerebral F-FDG PET/CT following surgical treatment of lumbar disc herniation.

We hypothesized that unilateral leg pain following surgical treatment of lumbar disc herniation (LDH) is associated with an increase in the glucose metabolism of the contralateral thalamus.

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The complexities of the sleep-pain relationship in adolescents: A critical review.

Chronic pain is a common and disabling condition in adolescents. Disturbed sleep is associated with many detrimental effects in adolescents with acute and chronic pain. While sleep and pain are known to share a reciprocal relationship, the sleep-pain relationship in adolescence warrants further contextualization within normally occurring maturation of several biopsychological processes. Since sleep and pain disorders begin to emerge in early adolescence and are often comorbid, there is a need for a comprehensive picture of their interrelation especially related to temporal relationships and mechanistic drivers. While existing reviews provide a solid foundation for the interaction between disturbed sleep and pain in youth, we will extend this review by highlighting current methodological challenges for both sleep and pain assessments, exploring the recent evidence for directionality in the sleep-pain relationship, reviewing potential mechanisms and factors underlying the relationship, and providing direction for future investigations. We will also highlight the potential role of digital technologies in advancing the understanding of the sleep and pain relationship. Ultimately, we anticipate this information will facilitate further research and inform the management of pain and poor sleep, which will ultimately improve the quality of life in adolescents and reduce the risk of pain persisting into adulthood.

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Towards Zebrafish Models of CNS Channelopathies.

Channelopathies are a large group of systemic disorders whose pathogenesis is associated with dysfunctional ion channels. Aberrant transmembrane transport of K, Na, Ca and Cl by these channels in the brain induces central nervous system (CNS) channelopathies, most commonly including epilepsy, but also migraine, as well as various movement and psychiatric disorders. Animal models are a useful tool for studying pathogenesis of a wide range of brain disorders, including channelopathies. Complementing multiple well-established rodent models, the zebrafish () has become a popular translational model organism for neurobiology, psychopharmacology and toxicology research, and for probing mechanisms underlying CNS pathogenesis. Here, we discuss current prospects and challenges of developing genetic, pharmacological and other experimental models of major CNS channelopathies based on zebrafish.

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The Impact of Duodenal Mucosal Vulnerability in the Development of Epigastric Pain Syndrome in Functional Dyspepsia.

An unidentified cause of functional dyspepsia (FD) is closely associated with medication resistance. Acid suppression is a traditional and preferential method for the treatment of FD, but the efficacy of this treatment varies between epigastric pain syndrome (EPS) and postprandial syndrome (PDS): it is efficient in the former but not much in the latter. Transepithelial electrical resistance (TEER), a surrogate of mucosal barrier function, was measured under pH 3 and pH 5 acidic conditions using duodenal biopsy specimens obtained from the patients with EPS and PDS and asymptomatic healthy controls. The infiltration of inflammatory cells to the duodenal mucosa was accessed by immunohistochemical analysis. The duodenal mucosal TEER in EPS patients was decreased by exposure to the acidic solution compared to that of the controls and the PDS patients. The decrease in TEER of the EPS patients was observed even under pH 5 weak acidic condition and was correlated to degree of the epigastric pain. Moreover, the duodenal mucosa of EPS patients presented an increase in mast cells and plasma cells that expressed Ig-E. Duodenal mucosal vulnerability to acid is likely to develop EPS.

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Data-Driven Path Analytic Modeling to Understand Underlying Mechanisms in COVID-19 Survivors Suffering from Long-Term Post-COVID Pain: A Spanish Cohort Study.

Pain can be present in up to 50% of people with post-COVID-19 condition. Understanding the complexity of post-COVID pain can help with better phenotyping of this post-COVID symptom. The aim of this study is to describe the complex associations between sensory-related, psychological, and cognitive variables in previously hospitalized COVID-19 survivors with post-COVID pain, recruited from three hospitals in Madrid (Spain) by using data-driven path analytic modeling. Demographic (i.e., age, height, and weight), sensory-related (intensity or duration of pain, central sensitization-associated symptoms, and neuropathic pain features), psychological (anxiety and depressive levels, and sleep quality), and cognitive (catastrophizing and kinesiophobia) variables were collected in a sample of 149 subjects with post-COVID pain. A Bayesian network was used for structural learning, and the structural model was fitted using structural equation modeling (SEM). The SEM model fit was excellent: RMSEA < 0.001, CFI = 1.000, SRMR = 0.063, and NNFI = 1.008. The only significant predictor of post-COVID pain was the level of depressive symptoms (β=0.241, = 0.001). Higher levels of anxiety were associated with greater central sensitization-associated symptoms by a magnitude of β=0.406 ( = 0.008). Males reported less severe neuropathic pain symptoms (-1.50 SD S-LANSS score, < 0.001) than females. A higher level of depressive symptoms was associated with worse sleep quality (β=0.406, < 0.001), and greater levels of catastrophizing (β=0.345, < 0.001). This study presents a model for post-COVID pain where psychological factors were related to central sensitization-associated symptoms and sleep quality. Further, maladaptive cognitions, such as catastrophizing, were also associated with depression. Finally, females reported more neuropathic pain features than males. Our data-driven model could be leveraged in clinical trials investigating treatment approaches in COVID-19 survivors with post-COVID pain and can represent a first step for the development of a theoretical/conceptual framework for post-COVID pain.

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The evolution of the British Journal of Anaesthesia: the first 100 years.

At this centenary of the British Journal of Anaesthesia (BJA) in 2023, six of its 12 editors/editors-in-chief detail developments over the decades that have led to the BJA becoming a high-impact international scientific journal. As a charity, the BJA supports academic research and training in anaesthesia, critical care, and pain medicine including funding of research grants and postgraduate education. Building on this foundation, the BJA continues to innovate as it aims to become fully electronic, expand into open access publishing, and increase the diversity of its editorial board.

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Promising Advances in Pharmacotherapy for Patients with Spinal Cord Injury-A Review of Studies Performed In Vivo with Modern Drugs.

Spinal cord injury (SCI) is a pathological neurological condition that leads to significant motor dysfunction. It is a condition that occurs as a result of tragic accidents, violent acts, or as a consequence of chronic diseases or degenerative changes. The current treatments for patients with SCI have moderate efficacy. They improve the quality of life of patients, but they are still doomed to long-term disability. In response to the modern directions of research on possible therapeutic methods that allow for the recovery of patients with SCI, a scientific review publication is needed to summarize the recent developments in this topic. The following review is focused on the available pharmacological treatments for SCIs and the problems that patients face depending on the location of the injury. In the following review, the research team describes problems related to spasticity and neuropathic pain; possible therapeutic pathways are also described for neuroprotection and the improvement of neurotransmission within the injured spinal cord, and the review focuses on issues related to oxidative stress.

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RgIA4 Prevention of Acute Oxaliplatin-Induced Cold Allodynia Requires α9-Containing Nicotinic Acetylcholine Receptors and CD3 T-Cells.

Chemotherapy-induced neuropathic pain is a debilitating and dose-limiting side effect. Oxaliplatin is a third-generation platinum and antineoplastic compound that is commonly used to treat colorectal cancer and commonly yields neuropathic side effects. Available drugs such as duloxetine provide only modest benefits against oxaliplatin-induced neuropathy. A particularly disruptive symptom of oxaliplatin is painful cold sensitivity, known as cold allodynia. Previous studies of the peptide, RgIA, and its analogs have demonstrated relief from oxaliplatin-induced cold allodynia, yielding improvement that persists even after treatment cessation. Moreover, underlying inflammatory and neuronal protection were shown at the cellular level in chronic constriction nerve injury models, consistent with disease-modifying effects. Despite these promising preclinical outcomes, the underlying molecular mechanism of action of RgIA4 remains an area of active investigation. This study aimed to determine the necessity of the α9 nAChR subunit and potential T-cell mechanisms in RgIA4 efficacy against acute oxaliplatin-induced cold allodynia. A single dose of oxaliplatin (10 mg/kg) was utilized followed by four daily doses of RgIA4. Subcutaneous administration of RgIA4 (40 µg/kg) prevented cold allodynia in wildtype mice but not in mice lacking the α9 nAChR-encoding gene, . RgIA4 also failed to reverse allodynia in mice depleted of CD3 T-cells. In wildtype mice treated with oxaliplatin, quantitated circulating T-cells remained unaffected by RgIA4. Together, these results show that RgIA4 requires both and CD3 T-cells to exert its protective effects against acute cold-allodynia produced by oxaliplatin.

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Lipoyl-Based Antagonists of Transient Receptor Potential Cation A (TRPA1) Downregulate Osteosarcoma Cell Migration and Expression of Pro-Inflammatory Cytokines.

Osteosarcoma is a heterogeneous tumor intimately linked to its microenvironment, which promotes its growth and spread. It is generally accompanied by cancer-induced bone pain (CIBP), whose main component is neuropathic pain. The TRPA1 ion channel plays a key role in metastasis and is increasingly expressed in bone cancer. Here, a novel TRPA1 inhibitor is described and tested together with two other known TRPA1 antagonists. The novel lipoyl derivative has been successfully assessed for its ability to reduce human osteosarcoma MG-63 cell viability, motility, and gene expression of the CIBP pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α). A putative three-dimensional (3D) model of the inhibitor covalently bound to TRPA1 is also proposed. The in vitro data suggest that the novel inhibitor described here may be highly interesting and stimulating for new strategies to treat osteosarcomas.

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Persistent opioid use after gender affirmation surgery.

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