Molecular Pain最新文献

{"title":"<i>In silico</i> exploration of bioactive secondary metabolites with anesthetic effects on sodium channels Nav 1.7, 1.8, and 1.9 in painful human dental pulp.","authors":"Ravinder S Saini, Rayan Ibrahim H Binduhayyim, Mohamed Saheer Kuruniyan, Artak Heboyan","doi":"10.1177/17448069251327824","DOIUrl":"10.1177/17448069251327824","url":null,"abstract":"<p><strong>Aim: </strong>To investigate the efficacy of medicinal plant bioactive secondary metabolites as inhibitors of voltage-gated sodium channels (Nav1.7, Nav1.8, and Nav1.9) in managing painful states of dental pulps.</p><p><strong>Methodology: </strong>Molecular docking, ADME prediction, toxicity profiling, and pharmacophore modeling were used to assess the binding affinities, pharmacokinetic properties, toxicological profiles, and active pharmacophores of the selected bioactive compounds.</p><p><strong>Results: </strong>Three compounds (Sepaconitine, Lappaconitine, and Ranaconitine) showed binding affinities (ΔG = -8.95 kcal/mol, -7.77 kcal/mol, and -7.44 kcal/mol, respectively) with all three Nav1.7, Nav1.8, and Nav1.9 sodium channels. The sepaconitine amine group formed hydrophobic interactions with key residues. The Lappaconitine benzene ring contributed to hydrophobic interactions and hydrogen bond acceptor interactions. The hydrophobic interactions of the ranaconitine amine group play a critical role with specific residues on Nav1.8 and Nav1.9.</p><p><strong>Conclusion: </strong>The natural fusicoccane diterpenoid derivatives Sepaconitine, Lappaconitine, and Ranaconitine are potential lead compounds for the development of novel analgesics as selective antihyperalgesic drugs, which will provide a new dental pharmacological intervention for managing painful dental pulp conditions. Further experimental validation and clinical studies that confirm the efficacy and safety of these compounds will strengthen their applicability in dental practice.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251327824"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring novel non-opioid pathways and therapeutics for pain modulation.","authors":"Isabella Alessi, Kaysie L Banton, Sliter J, Zaw-Mon C, Palacio Ch, Ryznar Rj, Bar-Or D","doi":"10.1177/17448069251327840","DOIUrl":"10.1177/17448069251327840","url":null,"abstract":"<p><p>The opioid crisis has highlighted the urgent need for alternative pain management strategies. This review explores novel non-opioid targets and pathways involved in pain modulation, highlighting advancements in understanding and therapeutic potential. Pain, a multifaceted phenomenon with nociceptive, neuropathic, and inflammatory components, involves intricate molecular signaling cascades. Key pathways reviewed include voltage-gated sodium channels (Nav1.7, Nav1.8, Nav1.9), inflammasome complexes (NLRP3), the kynurenine pathway, prostaglandins, and bradykinin-mediated signaling. Emerging therapeutics such as selective Nav channel blockers, NLRP3 inhibitors, kynurenine pathway modulators, EP receptor antagonists, and bradykinin receptor antagonists offer promising alternatives to opioids. Despite challenges in clinical translation, these developments signal a paradigm shift in pain management, with precision-focused therapies poised to address unmet needs. This review emphasizes the importance of integrating molecular insights into the development of safer, more effective analgesics, setting the stage for transformative advancements in non-opioid pain relief.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251327840"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938896/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGK1-HDAC4-HMGB1 signaling pathway in the spinal cord dorsal horn participates in diabetic neuropathic pain.","authors":"Mao-Biao Zhang, Jia-Li Chen, Jia-Hui Lu, Gai-Li Jia, Hong Cao, Jun Li","doi":"10.1177/17448069251321143","DOIUrl":"10.1177/17448069251321143","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to determine whether serum-and glucocorticoid-inducible kinase1 (SGK1) activation-dependent histone deacetylase 4 (HDAC4) phosphorylation, nucleocytoplasmic trafficking, and subsequent regulation of high-mobility group protein box 1 (HMGB1) expression are involved in type 2 diabetic neuropathic pain (DNP).</p><p><strong>Methods: </strong>The type 2 diabetic neuropathic pain model was established in rats by feeding them with a high-fat and high-sugar diet for 8 weeks and then fasting them for 12 h, followed by a single intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). SGK1 was inhibited in the spinal cord by intrathecal administration of the SGK1 inhibitor GSK-650394.</p><p><strong>Results: </strong>The present study revealed that pSGK1/tSGK1 was persistently upregulated in the spinal cord of rats with type-2 DNP. The downregulation of pSGK1/tSGK1 through the intrathecal injection of the SGK1 inhibitor GSK-650394 significantly ameliorated the pain hypersensitivity, relieved the abnormal expression of pHDAC4/tHDAC4 and HMGB1, and affected HDAC4 nucleocytoplasmic trafficking in DNP rats.</p><p><strong>Conclusion: </strong>Our data suggest that SGK1 in the spinal cord modulates type-2 DNP by regulating the HDAC4/HMGB1 pathway.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251321143"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11837076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression and anxiety in Chinese patients hospitalized with primary headache: A cross-sectional multicenter study.","authors":"Zhihua Jia, Dongjun Wan, Ziming Yin, Zhiliang Fan, Peng Xu, Xueqian Yuan, Min Chen, Dan Wang, Hebo Wang, Shengshu Wang, Shuhua Zhang, Ruozhuo Liu, Xiaolin Wang, Rongfei Wang, Hui Su, Xun Han, Zhe Yu, Yingji Li, Shengyuan Yu, Zhao Dong","doi":"10.1177/17448069251314271","DOIUrl":"10.1177/17448069251314271","url":null,"abstract":"<p><strong>Background: </strong>Primary headache and psychiatric diseases are bidirectional correlated. The real-world data of depression and anxiety in Chinese patients hospitalized for primary headache, considering all subtypes, remain unclear.</p><p><strong>Methods: </strong>This study enrolled patients attending eight Chinese headache centers from October 2022 to September 2023. A WeChat mini-program was designed to collect data. Headache was diagnosed and confirmed by two headache specialists. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 were used to assess depression and anxiety.</p><p><strong>Results: </strong>Overall, 1963 patients with primary headache were analyzed; the prevalence of depression and anxiety was 20.1% (396/1963) and 14.8% (290/1963), respectively. Of the 1963 patients, 217 (11.1%) had history of anxiety or depression and 184 (9.4%) had undergone assessments. Patients with both primary headache and depression were more likely to be women (77.8% vs 71.9%), experience more severe headache (numerical rating scale; 6.2 ± 1.9 vs 5.7 ± 1.9) and greater impacts on quality of life (Headache Impact Test-6; 65.3± 8.5 vs 58.1 ± 11.5). Those with both primary headache and anxiety exhibited similar results and were less educated. Depression and anxiety were more prevalent in chronic migraineurs (CM) than in episodic migraineurs (36.8% vs 16.9% and 28.9% vs 12.3%, respectively) and in those with chronic (CTTH) than in those with episodic tension-type headache (30.6% vs 15.1% and 20.1% vs 12.8%, respectively).</p><p><strong>Conclusion: </strong>Depression and anxiety are inadequately diagnosed and strongly associated with sex, severe headache, chronification and disability in patients with primary headache in China. To improve the health of patients with primary headaches, early screening for depression and anxiety is important.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251314271"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11815811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin relieves CFA-induced inflammatory pain by inhibiting the AP-1/c-Jun-CCL2-CCR2 pathway in the spinal dorsal horn.","authors":"Yi Zhu, Yinhong Jiang, Xinyu Lu, Siyu Li, Fujiaying Liu, Yidan Xu, Yue Tian, Liangliang Gao, Lei Wei","doi":"10.1177/17448069251323668","DOIUrl":"10.1177/17448069251323668","url":null,"abstract":"<p><p>Inflammatory pain is a pervasive clinical issue that severely diminishes individuals' quality of life. AP-1 (Activating protein-1) is a transcription factor composed of Jun and Fos proteins. Upregulation of AP-1/c-Jun activity is observed in a variety of diseases, particularly in inflammatory conditions. The CCL2 (C-C Motif Chemokine Ligand 2)/CCR2 (C-C Chemokine Receptor 2) axis plays a crucial role in regulating both peripheral and central inflammation. Curcumin, a natural compound derived from the roots of turmeric, possesses anti-inflammatory, antioxidant, and analgesic properties, making it effective for treating various disorders. However, the effects of curcumin on inflammatory pain and its potential mechanisms of action remain unclear. In this study, we utilized a CFA (Complete Freund's Adjuvant)-induced inflammatory pain model to investigate the effects of curcumin. We found that curcumin effectively reduced CFA-induced mechanical allodynia when administered via intrathecal injection. Behavioral assessments were performed using the Von Frey test. Western blot analysis was performed to detect variations in molecular expression, while immunofluorescence was employed to ascertain cellular localization. Intrathecal injection of the AP-1/c-Jun inhibitor T-5224, along with curcumin, resulted in a reduction in the levels of c-Jun, p-c-Jun, CCL2, and CCR2. Additionally, intrathecal injection of the CCR2 antagonist RS504393 also reduced the expression of CCL2 and CCR2. In summary, curcumin plays a significant role in analgesia within the CFA-induced inflammatory pain model. CCL2/CCR2 acts as a downstream mediator of AP-1/c-Jun. Curcumin can suppress the expression of AP-1/c-Jun, thereby inhibiting the expression of CCL2 and CCR2 in the spinal dorsal horn and contributing to the treatment of inflammatory pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251323668"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11869292/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143414630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of the neuropeptide receptor calcitonin receptor-like in the spinal cord via MLL2 in a mouse model of paclitaxel-induced peripheral neuropathy.","authors":"Salvador Sierra, Sara M Herz, Doan On, Mikhail G Dozmorov, M Imad Damaj, Javier Gonzalez-Maeso","doi":"10.1177/17448069251314857","DOIUrl":"10.1177/17448069251314857","url":null,"abstract":"<p><p>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). The density of the CGRP receptor is most prominent in the dorsal horn of the spinal cord, where it overlaps with the distribution of CGRP. However, the impact of chemotherapy treatment on expression of the CGRP receptor in the spinal cord remains unclear, as well as the potential therapeutic benefits of a CGRP receptor antagonist in an animal model of CIPN. Using a mouse model of paclitaxel-induced mechanical hypersensitivity, we show upregulation of <i>Calcitonin receptor-like receptor</i> (<i>Calcrl</i>) mRNA expression in the spinal cord, an event that occurred in association with upregulation of the H3K4 methyltransferase <i>MLL2</i>. 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 <i>Calcrl</i> 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.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"21 ","pages":"17448069251314857"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11795615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143189938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulation of LRRC8A in the anterior cingulate cortex mediates chronic visceral pain in adult male mice with neonatal maternal deprivation.","authors":"Jin-Nan Lu, Jing-Heng Dou, Zi-Long Yi, Lian Lian, Xing-Lei Ben, Fu-Chao Zhang, Guang-Yin Xu","doi":"10.1177/17448069251324645","DOIUrl":"10.1177/17448069251324645","url":null,"abstract":"<p><p>Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder primarily characterized by chronic visceral pain. Studies have reported that the anterior cingulate cortex (ACC) is involved in chronic visceral pain, however, the molecular mechanisms underlying this involvement remain largely unclear. In this study, we aimed to investigate the molecular mechanisms of the ACC in chronic visceral pain induced by neonatal maternal deprivation (NMD) in male mice. We showed that the expression of leucine-rich repeat-containing protein family member 8A (LRRC8A) at both mRNA and protein levels was significantly upregulated in the ACC of NMD male mice, with LRRC8A primarily co-localized in neurons. DCPIB, an inhibitor of LRRC8A, greatly alleviated chronic visceral pain. Moreover, the ATP concentration was significantly upregulated in the ACC of NMD male mice. However, LRRC8A was not involved in somatic pain induced by complete Freund's adjuvant (CFA) injection into the hind paw. In conclusion, our findings demonstrate that LRRC8A plays a critical role in regulating chronic visceral pain in NMD mice. These findings are expected to provide new ideas for the treatment of chronic visceral pain in IBS patients.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251324645"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11894642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of pain in lumbosacral stenosis and lifestyle-related factors on brain-derived neurotrophic factor expression profiles.","authors":"Dawid Sobański, Rafał Staszkiewicz, Małgorzata Sobańska, Damian Strojny, Beniamin Oskar Grabarek","doi":"10.1177/17448069241309001","DOIUrl":"https://doi.org/10.1177/17448069241309001","url":null,"abstract":"<p><p>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. The results showed significantly higher BDNF expression at both messenger ribonucleic acid (mRNA; fold change = +1.35 ± 0.23; <i>p</i> < 0.05) and protein levels in patients (28.98 ± 6.40 pg/mg) compared to controls (4.56 ± 1.98 pg/mg; <i>p</i> < 0.05). Furthermore, BDNF levels correlated positively with pain intensity reported by patients, with higher expression observed in those experiencing more severe pain. The study also explored the influence of lifestyle factors, such as smoking and alcohol consumption, and related diseases, such as diabetes, on BDNF expression. Smoking, alcohol use, and diabetes were associated with significantly elevated BDNF levels (<i>p</i> < 0.05). 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.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"21 ","pages":"17448069241309001"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Adaptation of the Reward System in Primary Dysmenorrhea.","authors":"Pei-Shan Hsu,Ching-Hsiung Liu,Ching-Ju Yang,Lin-Chien Lee,Wei-Chi Li,Hsiang-Tai Chao,Li-Fen Chen,Jen-Chuen Hsieh","doi":"10.1177/17448069241286466","DOIUrl":"https://doi.org/10.1177/17448069241286466","url":null,"abstract":"Introduction The brain's reward system (RS) reacts differently to pain and its alleviation. This study examined the correlation between RS activity and behavior during both painful and pain-free periods in individuals with primary dysmenorrhea (PDM) to elucidate their adaptive and maladaptive responses throughout the menstrual cycle. Methods Ninety-two individuals with PDM and 90 control participants underwent resting-state functional magnetic resonance imaging (rsfMRI) scans during their menstrual and peri-ovulatory phases. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analyses were used to evaluate RS responses. Psychological evaluations were conducted using the McGill Pain Questionnaire and the Pain Catastrophizing Scale. Results ReHo analysis showed higher values in the left putamen and right amygdala of the PDM group during the peri-ovulatory phase compared to the menstrual phase. ALFF analysis revealed lower values in the putamen of the PDM group compared to controls, regardless of phase. ReHo and ALFF values in the putamen, amygdala, and nucleus accumbens were positively correlated with pain scales during menstruation, while ALFF values in the ventral tegmental area inversely correlated with pain intensity. Those with severe PDM (pain intensity ≥ 7) displayed distinct amygdala ALFF patterns between pain and pain-free phases. PDM participants also had lower ReHo values in the left insula during menstruation, with no direct correlation to pain compared to controls. Discussion Our study highlights the pivotal role of the RS in dysmenorrhea management, exhibiting varied responses between menstrual discomfort and non-painful periods among individuals with PDM. During menstruation, the RS triggers mechanisms for pain avoidance and cognitive coping strategies, while it transitions to processing rewards during the peri-ovulatory phase. This demonstrates the flexibility of the RS in adapting to the recurring pain experienced by those with PDM.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":"59 1","pages":"17448069241286466"},"PeriodicalIF":3.3,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142219212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing Substance Levels and Pain Perception in Painless Labor: The Impact of Spinal Epidural Analgesia.","authors":"Fahmi Agnesha, Eti Nurwening Solikhah, Djayanti Sari, Rianza Ainunnisa","doi":"10.1177/17448069241273692","DOIUrl":"https://doi.org/10.1177/17448069241273692","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>This experimental study, conducted at a General Hospital in Indonesia, involved 60 expectant mothers in labor or in the third trimester, expected to give birth vaginally at Permata Hati Metro Hospital. Blood serum was used for analysis, and serum NO, TNF-α, and SP levels were assessed using ELISA kit.</p><p><strong>Results: </strong>There's a significant decrease in NO levels before and post-treatment in the SEA group compared to the control group (p < 0.05). However, no significant difference in TNF-α levels was observed between groups before and after treatment (p > 0.05). Additionally, there was no significant difference in SP levels between groups before treatment, but a significant difference was seen after treatment (p < 0.05). SEA significantly reduced labor pain compared to the control group (P < 0.05), with notable improvements in vital signs and APGAR scores, while also shortening labor duration (P < 0.001).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069241273692"},"PeriodicalIF":2.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}