Mol Pain
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Chemotherapy-induced peripheral neuropathy (CIPN) is a prevalent and severe side effect affecting cancer patients undergoing paclitaxel treatment. Growing evidence underscores the pivotal role of calcitonin-related peptide (CGRP) in the development of CIPN. Repeated administration of paclitaxel induces alterations in CGRP release from sensory neurons within the dorsal root ganglia (DRG). ⋯ This effect of repeated paclitaxel administration was also linked to an increase in the recruitment of MLL2, thereby enhancing levels of the active mark H3K4me2 at the Calcrl promoter. Furthermore, administration of the CGRP receptor antagonist BIBN4096 mitigated mechanical and cold hypersensitivity in paclitaxel-treated mice. Together, these observations suggest the CGRP receptor in the spinal cord as a potential target for reducing paclitaxel-induced neuropathic pain in animal models.
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This study investigated the role of brain-derived neurotrophic factor (BDNF) in patients with degenerative lumbar stenosis, focusing on its expression and correlation with pain intensity. The study examined 96 patients with lumbar stenosis and 85 control participants. BDNF levels in the yellow ligamentum flavum were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and western blot analysis. ⋯ These findings suggest that BDNF could serve as a biomarker for pain severity in degenerative lumbar stenosis at the protein level, although this was not consistently observed at the mRNA level; this highlights the potential for BDNF-targeted therapies in managing pain. Future research should involve larger longitudinal studies to validate these findings and explore therapeutic interventions. This study underscores the importance of considering molecular and lifestyle factors in the treatment of degenerative lumbar stenosis, aiming to improve patient outcomes through comprehensive, targeted approaches.
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Inflammation affects labor by influencing contractions and dilation. Pain, often linked to tissue ischemia, involves mediators like nitric oxide (NO), TNF-α, and substance P (SP). Neuraxial analgesia, including combined spinal epidural analgesia (SEA) with levobupivacaine, is preferred for its effectiveness and minimal side effects in painless labor. Understanding the impact of painless labor techniques on biomolecular processes such as NO, TNF-α, and substance P levels is crucial for improving pain management strategies. This study investigates these effects in parturients undergoing SEA with levobupivacaine, contributing to the development of novel pain medications and enhancing obstetric care. ⋯ In conclusion, SEA with levobupivacaine during painless labor reduces NO levels significantly and shows a trend of decreasing TNF-α and substance P levels, although not statistically significant, with clinical benefits for both patients and babies.
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Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the critical regulatory role of lysine-specific demethylase 6B (KDM6B) in the anterior cingulate cortex (ACC) in chronic visceral pain. ⋯ ChIP assay further indicated that KDM6B regulates NR2B expression by influencing the demethylation of H3K27me3. In summary, our findings underscore the critical role of KDM6B in regulating chronic visceral pain and anxiety-like behaviors in NMD mice. These insights provide a basis for further understanding the molecular pathways involved in IBS and may pave the way for targeted therapeutic interventions.
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We recently used Nav1.8-ChR2 mice in which Nav1.8-expressing afferents were optogenetically tagged to classify mechanosensitive afferents into Nav1.8-ChR2-positive and Nav1.8-ChR2-negative mechanoreceptors. We found that the former were mainly high threshold mechanoreceptors (HTMRs), while the latter were low threshold mechanoreceptors (LTMRs). In the present study, we further investigated whether the properties of these mechanoreceptors were altered following tissue inflammation. ⋯ Spontaneous action potential impulses were not observed in Nav1.8-ChR2-positive Aβ-fiber mechanoreceptors but occurred in Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors with a lower mechanical threshold in the saline goup, and a higher mechanical threshold in the CFA group. No significant change was observed in the mechanical sensitivity of Nav1.8-ChR2-positive and Nav1.8-ChR2-negative Aδ-fiber mechanoreceptors and Nav1.8-ChR2-positive C-fiber mechanoreceptors following hind paw inflammation. Collectively, inflammation significantly altered the functional properties of both Nav1.8-ChR2-positive and Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors, which may contribute to mechanical allodynia during inflammation.