Molecular Pain最新文献

{"title":"Viral vector-mediated interleukin 10 for gene therapy on chronic pain.","authors":"Megumi Kanao-Kanda, Hirotsugu Kanda, Shue Liu, Tomoyuki Kawamata, Keith A Candiotti, Shuanglin Hao","doi":"10.1177/17448069251390266","DOIUrl":"10.1177/17448069251390266","url":null,"abstract":"<p><p>Immunomodulatory molecules play a crucial role in the establishment and maintenance of chronic pain. Among these, anti-inflammatory interleukin-10 (IL-10) has emerged as one of therapeutic options to ameliorate pain state. Some components reduced pain through stimulating endogenous IL-10. However, IL-10 has a short half-life, which limits its long-term treatment of chronic pain. Gene therapy targeting <i>il10</i> gene expression has shown promise in preclinical studies. There are mainly two approaches to achieving successful transfection of target genes into cells, viral vectors and non-viral methods. Both Watkins and Milligan groups have well investigated and reviewed the non-viral mediated IL-10 delivery for chronic pain treatment, especially focusing on plasmid DNA encoding IL-10 including phase I clinical trial (XT-150; see Articles: Gene Therapy (2009) 16: 470-475; Neuromodulation (2012) 15: 520-526; and Front Immunol (2019) 10: 3009). Viral-vector-mediated gene therapy is a desirable route of administration to require local and long-term expression for chronic pain management. Therefore, in this review we focused on the utility of viral vector-mediated IL-10 expression in preclinical pain models. These studies consistently demonstrated the potential of IL-10-based gene therapy as a novel and sustained therapeutic approach for chronic pain.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251390266"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665025/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293051","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":"Utidelone induces mechanical and cold allodynia in mice via TRPA1 activation.","authors":"Wenwen Gao, Cunjin Su, Liya Dai, Jialong Tao, Yusong Zhang","doi":"10.1177/17448069251377633","DOIUrl":"10.1177/17448069251377633","url":null,"abstract":"<p><strong>Objective: </strong>Utidelone (UTD1), a recently approved epothilones analog in China for metastatic breast cancer, is endorsed in combination with capecitabine for metastatic breast cancer patients who have encountered first-line therapy failures. Despite its clinically verified therapeutic efficacy, it is concurrently associated with peripheral neuropathic pain, particularly affecting extremities. However, the etiology of UTD1-induced peripheral neuropathic pain remains unclear.</p><p><strong>Methods: </strong>The present investigation built a mouse pain model induced by UTD1, resulting in marked mechanical and cold allodynia.</p><p><strong>Results: </strong>Examination of the dorsal root ganglia unveiled a notable upregulation of TRPA1, accompanied by noteworthy alterations in oxidative stress-related markers, including ATF4, SOD2, CAT, and Cyt-C. The TRPA1 antagonist HC-030031, resulted in the alleviation of mechanical and cold allodynia in the UTD1-induced pain model, as well as two antioxidants, including Mito-tempo and edaravone.</p><p><strong>Interpretation: </strong>The present study will provide new strategies for pain relieving induced by UTD1.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251377633"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962170","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":"TLR3 mediates central sensitization in a chronic migraine model induced by repeated nitroglycerin through the ERK signaling pathway.","authors":"Bin Yang, Zhaoming Ge","doi":"10.1177/17448069251346373","DOIUrl":"10.1177/17448069251346373","url":null,"abstract":"<p><strong>Background: </strong>Studies have demonstrated that Toll-like receptor 3 (TLR3) plays a crucial role in neuropathic pain. However, there have been no relevant reports regarding the role of TLR3 in migraine chronification. This study aims to investigate the molecular mechanisms of TLR3 in the central sensitization of chronic migraine (CM).</p><p><strong>Methods: </strong>C57BL/6 male mice were used as models for chronic migraine (CM) disease, receiving an intraperitoneal injection of nitroglycerin (NTG) every other day. Calibrated von Frey filaments were employed to measure the pain threshold in the hind paw sole and periorbital region, enabling the assessment of mechanical allodynia. Western blot was employed to detect the expression changes of TLR3, TRAF6, TAK1, c-Fos, calcitonin gene-related peptide (CGRP), and the extracellular signal-regulated kinase (ERK) signaling pathway. Immunofluorescence was used to detect the cellular localization of TLR3 and the expression changes of central sensitization-related indicators, such as c-Fos and CGRP. In addition, we investigated the effects of TLR3 inhibitor (CU CPT4a), MEK inhibitor(PD98059), TRAF6 inhibitor(C25-140), and TAK1 inhibitor (Takinib) on chronic migraine-like behavior, and activation of the ERK pathway in the Trigeminal nucleus caudalis (TNC).</p><p><strong>Results: </strong>Recurrent injections of NTG resulted in a significant increase in the expression of TLR3, TRAF6, TAK1, CGRP, and c-Fos proteins, as well as the activation of the ERK signaling pathway. Concurrent inhibition of TLR3 function, TRAF6, TAK1, and the ERK pathway counteracted these changes and alleviated hyperalgesia in CM mice.</p><p><strong>Conclusions: </strong>Our findings suggest that TLR3 may play a role in central sensitization in CM mice by TRAF6-TAK1 axis modulating the ERK signaling pathway.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251346373"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128263","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":"Calcium channels in anesthesia management: A molecular and clinical review.","authors":"Mostafa Saberian, Afzal Shamsi, Mahdieh Mehrab Mohseni, Ashkan Taghizadehimani, Elham Shahidi Delshad","doi":"10.1177/17448069251343417","DOIUrl":"10.1177/17448069251343417","url":null,"abstract":"<p><p>Calcium channels play an essential role in the molecular and physiological mechanisms underlying anesthesia by mediating intracellular calcium ion (Ca²⁺) flux, which regulates key processes such as neurotransmitter release, neuronal excitability, and immune responses. Voltage-gated calcium channels (VGCCs) and ligand-gated calcium channels (LGCCs) are integral to the anesthetic process, with subtypes such as T-type VGCCs and NMDA receptors influencing consciousness and pain perception. This review emphasizes current evidence to highlight how anesthetic agents interact with calcium channels via direct inhibition and modulation of intracellular signaling pathways, such as phosphatidylinositol metabolism. Additionally, calcium channelopathies - genetic or acquired dysfunctions affecting VGCCs and LGCCs - pose challenges in anesthetic management, including arrhythmias, malignant hyperthermia, and altered anesthetic sensitivity. These findings underscore the critical need for precision medicine approaches tailored to patients with these conditions. While significant progress has been made in understanding the roles of calcium channels in anesthesia, knowledge gaps remain regarding the long-term implications of anesthetic interactions on calcium signaling and clinical outcomes. This review bridges foundational science with clinical practice, emphasizing the translational potential of calcium channel research for optimizing anesthetic strategies. By integrating molecular insights with emerging pharmacogenomic approaches, it provides a pathway for developing safer and more effective anesthesia protocols that enhance patient outcomes.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251343417"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973050","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":"RIPK3 regulates microglial polarization through the TLR4/MyD88 pathway in neuropathic pain.","authors":"Sihan E, Qingbiao Song, Zhaokun Zhang, Yingxia Liang","doi":"10.1177/17448069251377861","DOIUrl":"10.1177/17448069251377861","url":null,"abstract":"<p><p>Peripheral nerve injury activates microglia in the spinal, promoting microglial polarization and facilitating neuropathic pain progression. Necroptosis, a form of cell death, plays a crucial role in various neurological diseases and receptor-interacting protein kinases 3(RIPK3) a key molecular in the process. This study investigates to explore that RIPK3 regulates microglial polarization through the TLR4/MyD88 signaling pathway in neuropathic pain. By using a chronic constriction injury (CCI) model in mice, we found that peripheral nerve injury promoted M1 polarization and activated the TLR4/MyD88 pathway in spinal cord; in BV-2 microglia models, TNF-α/Z-VAD co-induction triggered M1 polarization through TLR4/MyD88 pathway, TLR4 antagonists suppressed these effects both in vivo and in vitro. Administration of GSK'872 (RIPK3 inhibitor) inhibited TLR4/MyD88 pathway, reduced microglial M1 polarization, promoted microglial M2 polarization and alleviated CCI-induced hyperalgesia. These findings suggest that necroptosis is a key cellular mechanism in peripheral injury-induced neuropathic pain and that RIPK3 regulates microglial polarization via the TLR4/MyD88 pathway, providing a new target for neuropathic pain treatment and clinical prevention.</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251377861"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12461077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962164","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":"Circulating microRNAs associated with acupuncture-induced Substance P reduction in chronic neck pain: Evidence for a neuroplasticity mechanism.","authors":"Seung-Nam Kim","doi":"10.1177/17448069251401661","DOIUrl":"10.1177/17448069251401661","url":null,"abstract":"<p><strong>Background: </strong>Acupuncture effectively reduces chronic neck pain and plasma Substance P (SP) levels, but upstream molecular mechanisms remain unknown.</p><p><strong>Objectives: </strong>We aimed to identify circulating microRNAs (miRNAs) associated with acupuncture-induced SP reduction and explore potential neuroplasticity mechanisms.</p><p><strong>Methods: </strong>We performed longitudinal plasma miRNA profiling (Affymetrix miRNA 4.0 Array, ~4600 miRNAs) in chronic neck pain patients: Acupuncture group (<i>n</i> = 3; 0, 4, 8 weeks) and Control group (<i>n</i> = 3; 0, 4 weeks). Linear Mixed-Effects Models (LMMs) tested associations between each miRNA and SP dynamics (miRNA × Time × Group interaction). Statistical significance was validated using permutation testing (2000 iterations).</p><p><strong>Results: </strong>Screening identified 53 miRNAs significantly associated with SP, validated by permutation testing (<i>p</i> < 0.001). Fourteen high-confidence miRNAs showed significant three-way interactions, indicating treatment-specific SP relationships. The most significant was miR-1302-6 (<i>p</i> = 7.65 × 10^-6), followed by miR-181b-2. These miRNAs displayed diverse temporal patterns: some (miR-196b, miR-6788) increased during treatment, while others (let-7d, miR-1302-6) decreased parallel to SP. Functional enrichment revealed striking convergence on neuroplasticity pathways: axon guidance (<i>p</i> = 2.61 × 10^-6), MAPK signaling (<i>p</i> = 4.18 × 10^-5), neuron projection development (<i>p</i> = 7.52 × 10^-10), and synaptic structures (<i>p</i> = 9.52 × 10^-12).</p><p><strong>Conclusions: </strong>This exploratory study provides first molecular evidence for an acupuncture-miRNA-SP axis in chronic pain. The enrichment of neuroplasticity pathways suggests acupuncture may induce structural remodeling of nociceptive circuits rather than simply suppressing inflammation, offering novel mechanistic insights and potential biomarkers for personalized acupuncture therapy. The trial was registered with the Korean Clinical Trial Registry (KCT0005363).</p>","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251401661"},"PeriodicalIF":2.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12696278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145541601","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}