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Oxygen is one of the most commonly used drugs by anesthesiologists. The World Health Organization (WHO) gave recommendations regarding perioperative oxygen administration, but the practice of oxygen use in anesthesia, critical emergency, and intensive care medicine remains unclear.
Learn More >Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.
Learn More >Neuropathic pain is a prevalent and severe chronic syndrome, often refractory to treatment, whose development and maintenance may involve epigenetic mechanisms. We previously demonstrated a causal relationship between miR-30c-5p upregulation in nociception-related neural structures and neuropathic pain in rats subjected to sciatic nerve injury. Furthermore, a short course of an miR-30c-5p inhibitor administered into the cisterna magna exerts long-lasting antiallodynic effects via a TGF-β1-mediated mechanism. Herein, we show that miR-30c-5p inhibition leads to global DNA hyper-methylation of neurons in the lumbar dorsal root ganglia and spinal dorsal horn in rats subjected to sciatic nerve injury. Specifically, the inhibition of miR-30-5p significantly increased the expression of the novo DNA methyltransferases DNMT3a and DNMT3b in those structures. Furthermore, we identified the mechanism and found that miR-30c-5p targets the mRNAs of DNMT3a and DNMT3b. Quantitative methylation analysis revealed that the promoter region of the antiallodynic cytokine TGF-β1 was hypomethylated in the spinal dorsal horn of nerve-injured rats treated with the miR-30c-5p inhibitor, while the promoter of Nfyc, the host gene of miR-30c-5p, was hypermethylated. These results are consistent with long-term protection against neuropathic pain development after nerve injury. Altogether, our results highlight the key role of miR-30c-5p in the epigenetic mechanisms' underlying neuropathic pain and provide the basis for miR-30c-5p as a therapeutic target.
Learn More >Human mesenchymal stem cell (hMSC) and extracellular vesicle (EV) therapy is a promising treatment for discogenic low back pain (LBP). Although promising, major obstacles remain to be overcome. Cellular senescence reduces self-renewal and multipotent potentials, and the senescence-associated secretory phenotype creates an inflammatory environment negatively affecting tissue homeostasis. Reducing senescence could therefore improve regenerative approaches. Ortho-Vanillin (o-Vanillin) has senolytic activity and anti-inflammatory properties and could be a valuable supplement to MSC and EV therapy. Here, we used direct co-culture experiments to evaluate proteoglycan synthesis, inflammatory mediators, and senescent cells in the presence or absence of o-Vanillin. EV release and transfer between hMSCs and intervertebral disc cells (DCs) was examined, and the effect on hMSC differentiation and DC phenotype was evaluated in the presence and absence of o-Vanillin. This study demonstrates that o-Vanillin affects cell communication, enhances hMSC differentiation and improves DC phenotype. Co-cultures of DCs and hMSCs resulted in increased proteoglycan synthesis, a decreased number of senescent cells and decreased release of the cytokines IL6 and 8. Effects that were further enhanced by o-Vanillin. o-Vanillin profoundly increased EV release and/or uptake by hMSCs and DCs. DC markers were significantly upregulated in both cell types in response to conditioned media of o-Vanillin treated donor cells. Collectively, this study demonstrates that o-Vanillin affects hMSC and DC crosstalk and suggests that combining hMSCs and senolytic compounds may improve the outcome of cell supplementation and EV therapy for LBP.
Learn More >Persistent low back pain (PLBP) is the biggest global cause of disability. Persons with PLBP experience biographic disruption and existential crisis. Guidelines recommend a biopsychosocial approach to management, with the emphasis on coping strategies.
Learn More >Postoperative pain after video-assisted thoracoscopic surgery (VATS) is common in lung cancer patients, and it is unclear whether cancer itself participates in pain regulation. Programmed cell death ligand-1 (PD-L1) expressed by tumors may be analgesic. Our study aimed to detect the association between PD-L1 and acute postoperative pain.
Learn More >Improving movement control might be a promising treatment goal during chronic non-specific low back pain (CLBP) rehabilitation. The objective of the study is to evaluate the effect of a single bout of game-based real-time feedback intervention on trunk movement in patients with CLBP.
Learn More >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.
Learn More >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.
Learn More >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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