Molecular Pain最新文献

{"title":"AMPK activation mitigates inflammatory pain by modulating STAT3 phosphorylation in inflamed tissue macrophages of adult male mice.","authors":"Hongchun Xiang, Yuye Lan, Liang Hu, Renjie Qin, Hongping Li, Tao Weng, Yan Zou, Yongmin Liu, Xuefei Hu, Wenqiang Ge, Hong Zhang, Hui-Lin Pan, Na-Na Yang, Wentao Liu, Guowei Cai, Man Li","doi":"10.1177/17448069251321339","DOIUrl":"10.1177/17448069251321339","url":null,"abstract":"<p><p>Inflammatory pain presents a significant clinical challenge. AMP-activated protein kinase (AMPK) is recognized for its capacity to alleviate inflammation by inhibiting transcription factors such as nuclear factor kappa B (NF-κB) and signal transducer and activator of transcription (STAT). Our prior research demonstrated that AMPK reduces inflammatory pain by inhibiting NF-κB activation and interleukin-1 beta (IL-1β) expression. However, the role of AMPK in regulating reactive oxygen species (ROS) and inducible nitric oxide synthase (iNOS) by modulating STAT3 phosphorylation in inflammatory pain remains inadequately understood. This study aims to investigate the role of AMPK in modulating STAT3 phosphorylation in the macrophages of inflamed tissues to mitigate inflammatory pain. A Complete Freund's Adjuvant (CFA)-induced inflammatory pain model was established by subcutaneous injection into the plantar surface of the left hindpaw of adult male mice. Behavioral tests of mechanical allodynia and thermal latency were used to determine nociceptive behavior. Immunoblotting quantified p-AMPK and iNOS expression levels. Nuclear translocation of p-STAT3(Ser727) and STAT3 in macrophages was assessed by western blot and immunofluorescence. ROS accumulation and mitochondrial damage in NR8383 macrophages were detected by flow cytometry. Lentivirus infection cells experiment was performed to transfect vectors encoding the STAT3 S727D mutants. Treatment with the AMPK activator AICAR alleviated CFA-induced inflammatory pain, enhanced AMPK phosphorylation, and reduced iNOS expression in inflamed skin tissues. AICAR effectively prevented STAT3 nuclear translocation while promoting the phosphorylation of STAT3 (Ser727) in the cytoplasm. In vitro studies with CFA-stimulated NR8383 macrophages revealed that AICAR increased STAT3(Ser727) phosphorylation, curtailed iNOS expression, and attenuated ROS accumulation and mitochondrial damage. Furthermore, the S727D mutation, which enhances STAT3 phosphorylation, replicated the protective effects of AICAR against CFA-induced oxidative stress and mitochondrial dysfunction. Our study shows that the AMPK acitvation downregulates iNOS expression by inhibiting the STAT3 nuclear translocation and promotes cytoplasmic STAT3(Ser727) phosphorylation, which reduces ROS expression and mitochondrial dysfunction, thereby alleviating inflammatory pain. These findings underscore the therapeutic potential of targeting AMPK and STAT3 pathways in inflammatory pain management.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251321339"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374457","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":"<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":"Unraveling the role of gut microbiota and plasma metabolites in fibromyalgia: Insights from Mendelian randomization and dietary interventions.","authors":"Mengqi Niu, Jing Li, Xiaoman Zhuang, Chenkai Yangyang, Yali Chen, Yingqian Zhang, Michael Maes","doi":"10.1177/17448069251332140","DOIUrl":"10.1177/17448069251332140","url":null,"abstract":"<p><p>Fibromyalgia (FM) is a complex disorder characterized by chronic pain, fatigue, and functional impairments, with unclear pathological mechanisms. Gut microbiota and plasma metabolites have been implicated in FM, but their causal relationships remain unexplored. This study aims to assess the causal relationships between gut microbiota, plasma metabolites, and FM using Mendelian randomization (MR) analysis and to explore potential mediating mechanisms. Public genome-wide association study data were analyzed using bidirectional MR. Associations between gut microbiota, plasma metabolites, and FM were evaluated, and multivariable MR identified mediating metabolites. Results were validated with inverse variance weighted, MR-Egger, and weighted median methods, with metabolic pathway enrichment analysis for further insights. MR identified protective associations between FM and four taxa (family <i>Enterobacteriaceae</i>, genus <i>Butyricicoccus</i>, genus <i>Coprococcus1</i>, and order <i>Enterobacteriales</i>) and risk associations with genus <i>Eggerthella</i> and genus <i>Ruminococcaceae UCG005</i>. Additionally, 82 plasma metabolites linked to pathways such as caffeine metabolism, α-linolenic acid metabolism, GLP-1, and incretin regulation were associated with FM. Mediation analysis revealed <i>Enterobacteriaceae</i> and <i>Enterobacteriales</i> influenced FM risk through 2,3-dihydroxypyridine and palmitoylcholine. Personalized dietary interventions, such as limiting caffeine intake, increasing omega-3 fatty acid consumption, adopting a low glycemic index diet, and reducing the intake of high-oxalate foods, may effectively alleviate FM-related symptoms by modulating metabolic pathways, reducing inflammation, and mitigating oxidative stress. This study highlights the intricate interactions between the gut microbiota and metabolic pathways, providing critical scientific evidence and actionable targets for clinical interventions, dietary management, and precision medicine approaches in FM treatment.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251332140"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12033522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674240","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":"Advanced cancer perineural invasion induces profound peripheral neuronal plasticity, pain, and somatosensory mechanical deactivation, unmitigated by the lack of TNFR1. Part. 1: Behavior and single-cell in vivo electrophysiology.","authors":"Silvia Gutierrez, Renee A Parker, Morgan Zhang, Maria Daniela Santi, Yi Ye, M Danilo Boada","doi":"10.1177/17448069251314738","DOIUrl":"10.1177/17448069251314738","url":null,"abstract":"<p><p>Patients with cancer perineural invasion (PNI) report greater spontaneous pain and mechanical allodynia. Here, we examine the impact of the disease on the peripheral sensory system, the excitability changes induced by PNI at the dorsal root ganglia, and the potential protective role of the absence of Tumor Necrosis Factor-α Receptor 1 (TNFR1). To study these effects, we use a murine model generated by injecting mouse oral cancer squamous cell carcinoma (MOC2) into the sciatic nerve (MOC2-PNI) in both male and female mice. We found that MOC2-PNI induces a profound change in the somatosensory landscape by deactivating/blocking the peripheral inputs while modulating the afferent's sensibility (tactile desensitization with concurrent nociceptive sensitization) and demyelination without inducing spontaneous activity. All these changes caused by MOC2-PNI are unmitigated by the absence of TNFR1. We conclude that MOC2-PNI induces an aberrant neuronal excitability state and triggers extreme gender-specific neuronal plasticity. These data allow us to speculate on the role of such plasticity as a powerful defense mechanism to prevent terminal sensory dysfunction, the rise of chronic pain, and extend animals' survivability.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251314738"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11898231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374456","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":"Cooling from noxious heat to normal skin temperatures excites a subpopulation of cutaneous Aβ-fiber low-threshold mechanoreceptors.","authors":"Akihiro Yamada, Ayaka I Yamada, Jennifer Ling, Jianguo G Gu","doi":"10.1177/17448069251359843","DOIUrl":"10.1177/17448069251359843","url":null,"abstract":"<p><p>Sensing cooling temperatures is achieved by primary afferent endings located in the skin and is essential for the survival of animals. TRPM8 channels, primarily expressed in cutaneous C-fibers, have been established as receptors for cooling temperatures, sensing innocuous cooling from the normal skin temperature near 30°C to 17°C, and noxious cooling below 17°C. A cooling sensation is also felt when skin temperatures are first elevated to higher temperatures, for example, noxious heat, and then cool down to the normal skin temperature near 30°C. It is currently not clear what types of cutaneous afferent fibers are involved in sensing the cooling from a high heat to the normal skin temperature. Cutaneous Aβ-fiber low-threshold mechanoreceptors (Aβ-LTMRs) are primarily involved in the sense of touch and are thought to play no role in cooling sensation. In the present study, we conducted the opto-electrophysiological recordings from the skin-nerve preparations made from the hindpaw glabrous skin of Nav1.8-ChR2 transgenic mice. In these transgenic mice, Nav1.8-ChR2-negative Aβ-fiber mechanoreceptors are primarily Aβ-LTMRs, and Nav1.8-ChR2-positive Aβ-fiber mechanoreceptors are mainly high-threshold mechanoreceptors (Aβ-HTMRs). Neither Aβ-LTMRs nor Aβ-HTMRs responded to temperature rising from 30°C to the noxious heat of 43°C. However, a subpopulation of Aβ-LTMRs, but not Aβ-HTMRs, robustly fires action potential impulses in response to the temperature drop from 43°C to 30°C. This finding reveals for the first time that a subpopulation of Aβ-LTMRs senses the cooling for a temperature drop from noxious heat to normal skin temperature.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251359843"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567553","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":"Loss and damage in large-diameter sensory neurons in the db/db diabetic mouse.","authors":"Reham M Filfilan, Mohammed A Nassar","doi":"10.1177/17448069251328521","DOIUrl":"10.1177/17448069251328521","url":null,"abstract":"<p><p>Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes. Half of DPN patients experience sensory deficits including loss of sensation and pain. Loss of sensation increases the risk of unnoticed foot injuries which combined with poor circulation and healing lead to amputation. Type 2 diabetes accounts for 50% of foot amputation highlighting the significant impact sensory loss can have on patients' quality of life. However, the cellular basis underlying sensory loss in DPN remains unclear. We characterized diabetes-induced neuronal loss and damage in dorsal root ganglia (DRG) in the db/db mouse model of type 2 diabetes. Morphometric characterization was carried out on two neuronal populations in lumbar DRGs of 32-week diabetic (db/db) mice. These are the N200-positive neurons, a marker for low and high-threshold mechanosensitive sensory and proprioceptive neurons, and peripherin (PRPH)-positive neurons, a marker for pain sensing neurons. In diabetic mice, N200-positive neurons were reduced by 30%. Furthermore, diabetes increased the percentage of N200-positive neurons with cytoplasmic vacuoles, a sign of damage and stress, by 2.44 fold. In addition, the average number of vacuoles was 1.6 fold higher in diabetic mice. Therapies aimed at reducing this loss could help patients better protect their limbs from injuries and thus reduce amputations.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251328521"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605913","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":"TRIM14-NF-κB pathway in the anterior cingulate cortex modulates comorbid depressive symptoms in chronic pain.","authors":"Jia-Hao Dai, Zhen-Hua Xu, Qiu-Lan Li, Jie Huang, Zheng Niu, Chen-Hao Zhang, Shufen Hu, Ren Sun, Yong-Chang Li","doi":"10.1177/17448069251335503","DOIUrl":"10.1177/17448069251335503","url":null,"abstract":"<p><p>Depression is commonly observed in individuals suffering from chronic pain, but the exact molecular mechanisms behind these symptoms are still not fully understood. This study highlights the important role of the TRIM14-NF-κB pathway in the anterior cingulate cortex (ACC) in regulating comorbid depressive symptoms associated with chronic pain. Our results show that the CFA model induces both chronic pain and depression-like behaviors in mice, with significant activation of the ACC brain regions. Specifically, the protein expression of TRIM14 was notably elevated in the ACC of CFA mice. Furthermore, reducing TRIM14 expression alleviated both chronic pain and depression-like behaviors in these mice. In addition, we also discovered that NF-κB may act as a downstream target of TRIM14, as silencing TRIM14 expression led to a reduction in the levels of phosphorylated NF-κB. Notably, inhibiting NF-κB produced similar improvements in chronic pain and depression-like behaviors, mirroring the effects observed with TRIM14 knockdown. In summary, our findings emphasize the critical role of the TRIM14-NF-κB pathway in regulating chronic pain and depression-like behaviors in the CFA mouse model. These insights provide a foundation for further exploration of the molecular mechanisms underlying chronic pain and depression, and may guide the development of targeted therapeutic strategies.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251335503"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12035169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811826","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":"Unraveling the PVN^Glu-PrL^Glu circuit: A new frontier in chronic pain management for lumbar disc herniation.","authors":"Qianliang Wang, Jianpeng Chen, Kang Jia, Yujian Peng, Yuanbin Wang, Qianqian Chen, Jun Yan","doi":"10.1177/17448069251342984","DOIUrl":"10.1177/17448069251342984","url":null,"abstract":"<p><p>Lumbar disc herniation (LDH) refers to a pathological state in which the nucleus pulposus (NP) protrudes, leading to compression or irritation of nerve roots. This condition manifests with clinical symptoms including lower back and leg pain, hyperalgesia, and altered sensory perceptions. Depending upon clinical observations, the administration of centrally acting analgesic has been associated with the alleviation of pain symptoms LDH patients. The central nervous system sensitization performs a crucial role in pain-regulating perception in LDH. Nevertheless, the precise neural circuitry and mechanism of action remain enigmatic. In the present study, we observed the activation of glutamatergic neurons in the Paraventricular nucleus of the hypothalamus (PVN) and Prelimbic cortex (PrL) in LDH rats. Experimental validation using viral tracers confirmed the existence of a projection pathway between the PVN and PrL. Inhibition of the input from PVN glutamatergic neurons to PrL glutamatergic neurons alleviates chronic pain in LDH, whereas activation of the PVN^Glu-PrL^Glu projection induces chronic pain in rats. These findings imply a pivotal role for the PVN^Glu-PrL^Glu circuit in the regulation of chronic pain in LDH.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251342984"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019096","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":"Preoperative reactive oxygen species exacerbate postoperative hyperalgesia by aggravating neuroinflammation through galectin-3.","authors":"Xuemei Zheng, Bin Shu, Ai Yan, Yonggang Liang, Niannian Huang, Houping Wang, Weilong Hong, Yongqin Chen, He Huang, Guangyou Duan","doi":"10.1177/17448069251353026","DOIUrl":"10.1177/17448069251353026","url":null,"abstract":"<p><p>Patients with preoperative pathological conditions such as anxiety, depression, and sleep disorders experience more severe postoperative pain, suggesting that preoperative pathological changes in patients may affect postoperative pain. However, the potential pathophysiological changes associated with postoperative pain remain unknown. Here, this study initially employed clinical research to investigate potential pathophysiological changes related to postoperative pain. Subsequently, animal behavioral experiments and mechanistic explorations were conducted accordingly. Pregnant women undergoing cesarean sections who could provide preoperative cerebrospinal fluid were selected as subjects. Preoperative cerebrospinal fluid proteomics, postoperative pain intensity, and neutrophil-to-lymphocyte ratio (NLR) were analyzed. Rats were used to model the corresponding preoperative pathological state. Mechanical pain thresholds were measured after plantar incision and spinal cords were harvested for analysis. Clinical studies showed that one-quarter of the proteins positively correlated with postoperative pain were related to reactive oxygen species (ROS). Furthermore, the NLR-Ratio, reflecting postoperative inflammation level, increased with the severity of postoperative pain. Establishing a preoperative ROS-increased model with oxidant t-BOOH enhanced postoperative acute mechanical hyperalgesia and spinal neuroinflammation in rats. Conversely, preoperative administration of antioxidant VE, reducing ROS, alleviated postoperative hyperalgesia and spinal neuroinflammation. galectin-3 inhibitors mitigated postoperative hyperalgesia and neuroinflammation in the preoperative ROS-increased model. Additionally, The effects of galectin-3 on pain sensitization and pro-inflammation in vitro were mediated by the TLR4 receptor. Thus, this study demonstrated that preoperative ROS exacerbated postoperative hyperalgesia via galectin-3-mediated neuroinflammation, suggesting that galectin-3 may be a potential therapeutic target for alleviating postoperative pain in clinical patients.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251353026"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144285457","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}