Molecular Pain最新文献

Pain and Inflammatory Biomarkers: Phytoactive Therapeutics and Drug Delivery Advances. 疼痛和炎症生物标志物：植物活性治疗和药物传递进展。

IF 3.8 3区医学

Molecular Pain Pub Date : 2026-07-15 DOI: 10.1177/17448069261466889

Deependra Soni, Sumathi Poleboina, Anshita Gupta, Chanchal Deep Kaur

引用次数: 0

EXPRESS: Precursor signaling redefined: proneurotrophin-3, not neurotrophin-3, in primary sensory neurons as an instigator in neuropathic pain. EXPRESS：前体信号重新定义：原eurotrophin-3，而不是神经营养因子-3，在初级感觉神经元中作为神经性疼痛的诱因。

IF 3.8 3区医学

Molecular Pain Pub Date : 2026-06-05 DOI: 10.1177/17448069261460645

Huijie Shang, Ruhika Iyer, Bing Wang, Yuan-Xiang Tao

{"title":"EXPRESS: Precursor signaling redefined: proneurotrophin-3, not neurotrophin-3, in primary sensory neurons as an instigator in neuropathic pain.","authors":"Huijie Shang, Ruhika Iyer, Bing Wang, Yuan-Xiang Tao","doi":"10.1177/17448069261460645","DOIUrl":"10.1177/17448069261460645","url":null,"abstract":"Neurotrophin-3 (NT3), one member of the nerve growth factor family of neurotrophins, is initially synthesized as a large precursor, termed proneurotrophin-3 (proNT3), which undergoes proteolytic cleavage to generate mature NT3. A growing body of evidence suggests that proNT3 and its mature form, NT3, have opposing roles in the nervous system. A systematic literature search of PubMed was conducted using predefined search terms related to NT3, proNT3, expression, dorsal root ganglion (DRG) and pain. The role of NT3 in neuropathic pain has been debated in earlier studies. Importantly, more recent studies have shown that proNT3, rather than NT3, is expressed in the DRG. In this review, we delineate the expression and distribution pattern of proNT3 in primary sensory neurons of the DRG under normal conditions, as well as its upregulation in injured DRG following peripheral nerve injury. We highlight that DRG proNT3 upregulation is required for the development and maintenance of neuropathic pain and discuss the role of C-C chemokine ligand 2 in mediating the contribution of proNT3-triggered TrkC activation to neuropathic pain in the DRG.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261460645"},"PeriodicalIF":3.8,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176074","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}

引用次数: 0

EXPRESS: Assessing Pain Sensitivity with COX-2 Biomarkers: A Novel Approach in Healthy Volunteers. EXPRESS：用COX-2生物标志物评估疼痛敏感性：一种健康志愿者的新方法

IF 2.8 3区医学

Molecular Pain Pub Date : 2026-06-05 DOI: 10.1177/17448069261461222

Maryam Mady, Christopher Henni, Taylor Pape, Omowunmi Sadik

{"title":"EXPRESS: Assessing Pain Sensitivity with COX-2 Biomarkers: A Novel Approach in Healthy Volunteers.","authors":"Maryam Mady, Christopher Henni, Taylor Pape, Omowunmi Sadik","doi":"10.1177/17448069261461222","DOIUrl":"https://doi.org/10.1177/17448069261461222","url":null,"abstract":"Quantifying pain is challenging due to its subjective nature. An established baseline of COX-2 levels in healthy subjects under controlled thermal pain stimulation will help bridge subjective pain assessment and objective biological measurements. 34 healthy students (aged from 17 to 21 years) participated in two thermal-induced pain protocols: (i) a water bath (ranging from 29 to 47 °C), (ii) internal wrist stimulation via a TSA-II thermal probe. Pain assessment was assessed via the visual analog scale (VAS). A strong positive correlation was observed between temperature and VAS scores (Pearson's r = 0.94, p<0.001). Temperature and immersion time in the water bath protocol showed a strong inverse correlation (r=-0.95, p<0.001). The mean COX-2 levels in water bath and TSA-II experiments were 1.88 ± 0.81 ng/mL (95% CI: 1.62 to 2.14) and 2.16 ± 0.77 ng/mL (95% CI: 1.92 to 2.40), respectively. These values are 50 to 2000-fold lower than those reported in the prior emergency-room-based acute pain studies. Linear mixed-effects models demonstrated that temperature was the only significant predictor of VAS (p < 0.001), while COX-2 was not. Whereas, COX-2 expression was not explained by VAS or temperature, indicating stable baseline levels. This work has established an exploratory baseline study for COX-2 levels in healthy subjects. This stark contrast highlights the potential to discriminate between baseline healthy and pain states, representing a step toward the development of biomarker-based tools for assessment.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261461222"},"PeriodicalIF":2.8,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176004","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}

引用次数: 0

EXPRESS: A Road to Recovery: Transient Receptor Potential (TRP) Channels as Therapeutic Avenues for Spinal Cord Injury. 表达：恢复之路：短暂受体电位（TRP）通道作为脊髓损伤的治疗途径。

IF 2.8 3区医学

Molecular Pain Pub Date : 2026-02-01 DOI: 10.1177/17448069261422992

Mohammad Amin Manavi, Amirhossein Charmchi, Reza Yegani, Fatemeh Nejati, Razieh Mohammad Jafari, Ahmad Reza Dehpour

引用次数: 0

EXPRESS: Assessment of Pain-Related Biomarkers in Migraine and Tension Headache Patients Pre- and Post-Botulinum Toxin Therapy. EXPRESS：评估偏头痛和紧张性头痛患者在肉毒杆菌毒素治疗前后的疼痛相关生物标志物。

IF 2.8 3区医学

Molecular Pain Pub Date : 2026-01-27 DOI: 10.1177/17448069261422070

Afrah Abdulsahib Abbas, Fawaz Aswad, Taghreed Zaidan

{"title":"EXPRESS: Assessment of Pain-Related Biomarkers in Migraine and Tension Headache Patients Pre- and Post-Botulinum Toxin Therapy.","authors":"Afrah Abdulsahib Abbas, Fawaz Aswad, Taghreed Zaidan","doi":"10.1177/17448069261422070","DOIUrl":"https://doi.org/10.1177/17448069261422070","url":null,"abstract":"This study aimed to evaluate the therapeutic impact of Onabotulinumtoxin A (botulinum toxin) injections in patients suffering from chronic migraine and chronic tension-type headache, while assessing changes in salivary pain biomarkers-calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP). A total of 45 subjects were recruited: 25 diagnosed with chronic migraine and 20 with chronic tension-type headache, based on criteria from the International Classification of Headache Disorders (ICHD-3 and ICHD-2 revisions, respectively). Diagnosis confirmation was supported by MRI or CT imaging to exclude other etiologies. Salivary CGRP and PACAP levels were measured before and after botulinum toxin administration using enzyme-linked immunosorbent assay (ELISA). In this open-label, uncontrolled design, results showed a statistically significant reduction (p < 0.05) in both biomarkers post-treatment across both patient groups. Onabotulinumtoxin A demonstrated apparent effectiveness as a prophylactic therapy, contributing to notable improvement in headache symptoms. Among all clinical parameters evaluated, orofacial pain showed the highest responsiveness to treatment.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261422070"},"PeriodicalIF":2.8,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053256","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}

引用次数: 0

Exploring frequency-dependent and dynamic changes in brain connectivity of chronic back pain patients using degree centrality analysis. EXPRESS：利用度中心性分析探讨慢性背痛患者脑连接的频率依赖性和动态变化。

IF 2.8 3区医学

Molecular Pain Pub Date : 2026-01-01 Epub Date: 2025-12-19 DOI: 10.1177/17448069251412603

Hanjun Hu, Luoyu Wang, Jiayi Deng, Yi Lin, Xue Tang, Xiuhong Ge, Zhongxiang Ding

{"title":"Exploring frequency-dependent and dynamic changes in brain connectivity of chronic back pain patients using degree centrality analysis.","authors":"Hanjun Hu, Luoyu Wang, Jiayi Deng, Yi Lin, Xue Tang, Xiuhong Ge, Zhongxiang Ding","doi":"10.1177/17448069251412603","DOIUrl":"10.1177/17448069251412603","url":null,"abstract":"Background: Chronic Back Pain (CBP) may lead to a reorganization of brain function, which can be observed through the indicator of degree centrality (DC). Traditional pain research has predominantly focused on static measurements of brain function within classical frequency bands, which may not fully capture the complexities of chronic pain. This study not only employed static frequency division but also incorporated dynamic analyses to capture the evolving nature of brain activity in chronic pain conditions.Methods: This study included a total of 31 patients with CBP and 33 age- and gender-matched healthy controls. Spontaneous brain activity was investigated by traditional DC, DC in subfrequency bands (slow-5, slow-4) and dynamic DC (dDC). Differences in brain regions between the two groups were obtained using two-sample t-tests. The association of abnormal brain regions with pain intensity and psychological tests were analyzed in parallel.Results: Compared to classical frequency band, the number of brain regions with changes in DC values in the slow-5 frequency band is greater. The right angular gyrus was found in both the slow-5 frequency band and the classical frequency band, while the left putamen was only found in the slow-5 frequency band. The dDC values were changed in left hippocampus, and right putamen, which were all different from the brain regions that the static DC (sDC) value altered.Conclusion: This study demonstrates that incorporating frequency and dynamic analysis in addition to traditional DC metrics can better understand the functional characteristics of the brain in CBP.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251412603"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12833176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794434","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}

引用次数: 0

Piezo1-mediated neuroexcitation via collaboration with KCa1.1 and Nav1.9 currents in myelinated Ah-type of trigeminal ganglion neurons in rats: Mechanistic insights with sex-specific effects. 大鼠三叉神经节ah型髓鞘神经元通过KCa1.1和Nav1.9电流介导的piezo1介导的神经兴奋：具有性别特异性效应的机制见解。

IF 2.8 3区医学

Molecular Pain Pub Date : 2026-01-01 Epub Date: 2025-12-12 DOI: 10.1177/17448069251410754

Yang Liu, Yao Song, Ximeng Ren, Meng Li, Shuangshuang Liu, Zixuan Li, Dapeng Ding, Xiaolong Lu

{"title":"Piezo1-mediated neuroexcitation via collaboration with KCa1.1 and Nav1.9 currents in myelinated Ah-type of trigeminal ganglion neurons in rats: Mechanistic insights with sex-specific effects.","authors":"Yang Liu, Yao Song, Ximeng Ren, Meng Li, Shuangshuang Liu, Zixuan Li, Dapeng Ding, Xiaolong Lu","doi":"10.1177/17448069251410754","DOIUrl":"10.1177/17448069251410754","url":null,"abstract":"Introduction: It has well been documented that sex-related difference in the prevalence of migraine is widely accepted with more commonly seen in female patients. Although trigeminal ganglion (TG) neurons are the key players in the etiology of migraine, the underlying pathophysiology remains under debate so far.Methods: Myelinated Ah-type TG neurons were identified by the waveform characters of action potential (AP) conjugated with pharmacological validation using whole-cell patch techniques.Results: The results showed that AP duration and current derivative for repolarization were markedly increased by 3 µM Yoda1 along with the increased firing frequency of repetitive discharge that could be abolished by 3 µM GsMTx4. Although Yoda1 concentration-dependently increased the peaks of Ca2+ currents, the blocker for Ca2+ channel ω-Conotoxin did not alter the AP waveform characters and discharge profiles, whereas Yoda1-mediated changes in AP waveform trajectory and repetitive discharge could be completely reversed by 1.0 µM Iberiotoxin, a selective KCa1.1 blocker, suggesting that Piezo1-induced Ca2+ influx can activate KCa1.1 via presumably channel coupling. Additionally, Ah-type TG neurons functionally expressed Nav1.9/Nav1.8 in all tested neurons and their peaks were significantly increased by 3 µM Yoda1 and completely blocked by 3 µM GsMTx4.Conclusion: These datasets have demonstrated Piezo1-mediated neuroexcitation of female-specific subpopulation of myelinated Ah-type TG neurons due at least to the coupling between N-type Ca2+ channel and KCa1.1 and functional upregulation of Nav1.9, which uncovers an additional insights for higher incidence of migraine in woman.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251410754"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145743452","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}

引用次数: 0

Beyond sodium channel blockade: Flavonoid as alternative local anesthetic candidates of lidocaine. 超越钠通道阻断：类黄酮作为利多卡因局部麻醉剂的备选。

IF 2.8 3区医学

Molecular Pain Pub Date : 2026-01-01 Epub Date: 2025-12-19 DOI: 10.1177/17448069251412600

Mamoru Takeda, Syogo Utugi, Ryou Toyota, Yukito Sashide

{"title":"Beyond sodium channel blockade: Flavonoid as alternative local anesthetic candidates of lidocaine.","authors":"Mamoru Takeda, Syogo Utugi, Ryou Toyota, Yukito Sashide","doi":"10.1177/17448069251412600","DOIUrl":"10.1177/17448069251412600","url":null,"abstract":"When conventional drug-based Western medicine proves ineffective, complementary and alternative medicine (CAM), including herbal medicine and acupuncture, often gains prominence. Phytochemicals, plant-derived compounds synthesized for self-protection against environmental stressors like ultraviolet radiation and insects, have also shown numerous physiological benefits in humans. Among these, flavonoid compounds - abundant in fruits and vegetables - have garnered significant research interest due to their reported biological activities, such as antioxidant, anti-inflammatory, and anticancer effects. Recent in vitro studies have provided substantial evidence that flavonoids modulate the activity of various ion channels. These channels are crucial for the generation and conduction of activation and action potentials in excitable cells, including those involved in pain transmission. These findings strongly suggest that flavonoids could serve as novel therapeutic agents for pain relief, potentially replacing existing local anesthetics. This paper discusses recent in vivo neurophysiological findings which reveal the potential of flavonoids to substitute existing local anesthetics in nociceptive and inflammatory pain. We explore the possibility of developing new drugs with fewer side effects by focusing on the common chemical structure of flavonoids, addressing the shortcomings of current anesthetics, and outlining future prospects.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069251412600"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12812192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794489","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}

引用次数: 0

Top-down descending modulation of dorsal spinal excitatory transmission from the insular cortex. EXPRESS：从岛叶皮层自上而下下行调节背侧脊髓兴奋性传递。

IF 3.8 3区医学

Molecular Pain Pub Date : 2026-01-01 Epub Date: 2026-02-20 DOI: 10.1177/17448069261428918

Qi-Yu Chen, Ren-Hao Liu, Shiwen Xue, Min Zhuo

{"title":"Top-down descending modulation of dorsal spinal excitatory transmission from the insular cortex.","authors":"Qi-Yu Chen, Ren-Hao Liu, Shiwen Xue, Min Zhuo","doi":"10.1177/17448069261428918","DOIUrl":"10.1177/17448069261428918","url":null,"abstract":"The insular cortex (IC), a critical hub for nociception, emotion, and cognition processing, has emerged as a key role in the descending modulation of spinal cord excitability. Although previous studies have suggested that IC may influence spinal nociceptive reflexes through direct or indirect top-down pathways, the specific effects of IC stimulation on spinal nociceptive transmission remain unclear. In this study, by combining in vivo whole-cell patch-clamp, behavioral and morphological approaches, we identified a direct projection from the IC to the contralateral dorsal spinal cord. To determine whether IC activation affect the spinal nociceptive reflex, we measured the spinal nociceptive tail-flick (TF) reflex during IC stimulation. We found that activating the IC by electric stimulation did not significantly alter the spinal TF reflex. Furthermore, in vivo whole-cell patch-clamp recordings from spinal dorsal horn neurons revealed that IC stimulation produced delayed inhibition of spontaneous excitatory transmission in some neurons, while exciting or having no significant effect on others. These results indicate that the top-down modulation from the IC to the spinal cord is not uniformly facilitatory, distinguishing it from the consistently facilitatory effects observed in the anterior cingulate cortex (ACC)-spinal cord projection.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261428918"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13009838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259019","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}

引用次数: 0

Study on the role and mechanism of the IL-10-IRF-8 signaling pathway in bone marrow mesenchymal stem cell therapy for pain in CCD rats. 表达：IL-10-IRF-8信号通路在骨髓间充质干细胞治疗CCD大鼠疼痛中的作用及机制研究

IF 3.8 3区医学

Molecular Pain Pub Date : 2026-01-01 Epub Date: 2026-02-27 DOI: 10.1177/17448069261432034

Yican Yang, Mutong Wang, Shuai Guo, Yan Feng, Yang Zhang, Shouwei Yue

{"title":"Study on the role and mechanism of the IL-10-IRF-8 signaling pathway in bone marrow mesenchymal stem cell therapy for pain in CCD rats.","authors":"Yican Yang, Mutong Wang, Shuai Guo, Yan Feng, Yang Zhang, Shouwei Yue","doi":"10.1177/17448069261432034","DOIUrl":"10.1177/17448069261432034","url":null,"abstract":"Purpose: To investigate the analgesic effects and mechanisms of BMSCs-IL-10+ administered via intrathecal injection in CCD rats.Patients and methods: After CCD surgery, rats were administered intrathecal injections of PBS, BMSCs, BMSCs-IL-10+, BMSCs-IL-10++Anti-IL-10, LV-IRF-8, and LV-IRF-8+IL-10. Pain was assessed by measuring the mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Glial cell activation and M2 microglial polarization were evaluated by immunofluorescence staining of Iba-1, GFAP, and Arg-1, and by WB for Iba-1 and Arg-1. Spinal cord inflammation was assessed by PCR analysis of TGF-β, TNF-α, and IL-1β expression.Results: Compared with the CCD+PBS group, intrathecal injection of both BMSCs and BMSCs-IL-10+ significantly alleviated CCD-induced mechanical and thermal pain. However, the analgesic effect of the BMSCs group markedly decreased after 4 days, while the BMSCs-IL-10+ group lasted at least 14 days. The BMSCs-IL-10+ group significantly upregulated the expression of TGF-β while downregulating TNF-α and IL-1β, inhibiting glial cell activation and promoting M2 microglia polarization. These effects were superior to the BMSCs group and could be abolished by anti-IL-10 antibody. IRF-8 overexpression exacerbated pain and inflammation in CCD rats, but the combined application of IL-10 protein reversed this impact.Conclusion: IL-10 is a key cytokine mediating the analgesic effects of BMSCs. Transplantation of BMSCs-IL-10+ cells reduces glial activation, alleviates neuroinflammation, and relieves neuropathic pain by enhancing IL-10 expression and suppressing IRF-8.","PeriodicalId":19010,"journal":{"name":"Molecular Pain","volume":" ","pages":"17448069261432034"},"PeriodicalIF":3.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13039620/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308135","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}

引用次数: 0