Neurobiology of Pain最新文献

White matter differences in motor and affective-motivational networks of pain-indifferent carriers of the R221W mutation R221W突变的疼痛无关携带者在运动和情感动机网络中的白质差异

Neurobiology of Pain Pub Date : 2026-03-28 DOI: 10.1016/j.ynpai.2026.100211

Arnas Tamasauskas , Irene Perini , Jan Minde , Simon S. Keller , Nicholas Fallon , Bernhard Frank , India Morrison , Andrew Marshall

{"title":"White matter differences in motor and affective-motivational networks of pain-indifferent carriers of the R221W mutation","authors":"Arnas Tamasauskas , Irene Perini , Jan Minde , Simon S. Keller , Nicholas Fallon , Bernhard Frank , India Morrison , Andrew Marshall","doi":"10.1016/j.ynpai.2026.100211","DOIUrl":"10.1016/j.ynpai.2026.100211","url":null,"abstract":"<div><div>The R221W mutation on the nerve growth factor gene results in reduced peripheral C-nociceptor density and behavioural indifference to painful stimuli. While functional neuroimaging has revealed altered cortical and sub-cortical pain processing in R221W carriers, structural white matter changes remain unexplored and may suggest an anatomical basis of symptoms. Heterozygous R221W carriers’ (n = 11) and matched controls’ (n = 11) diffusion MRI data were compared using fixel-based analysis, and complimentary edge and node analyses using graph theory and network-based statistics. Whole-brain and region of interest (ROI) fixel-based analyses revealed significantly reduced fibre density and fibre-bundle cross-section in brainstem motor tracts of R221W carriers, encompassing the corticospinal pathways, corona radiata, external capsule, cerebellar peduncles, and pontine crossing (p < 0.05). Graph theory analysis of pain-processing ROIs demonstrated significantly reduced node degree and betweenness centrality in the Left Anterior Cingulate Cortex (ACC) of R221W carriers, indicating structural isolation of this affective-motivational hub. Network-based statistics identified significantly stronger connectivity between the Right Thalamus and Right ACC in R221W carriers, in contrast to weaker connectivity connecting the Right Thalamus to the Left ACC and Left Insula (p < 0.05). These findings indicate potentially reduced brainstem motor tract integrity and altered cortical network topology, specifically the structural isolation of the Left ACC. This, alongside potentially compensatory right-sided thalamo-cortical connectivity and preserved sensory afferent pathways, supports a model of R221W pain indifference as motor under-reactivity rather than sensory insensitivity.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"20 ","pages":"Article 100211"},"PeriodicalIF":0.0,"publicationDate":"2026-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147584836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Differential Cortico-Thalamic reorganization in Opioid-Induced hyperalgesia and neuropathic pain male rats 阿片类药物致痛觉过敏和神经性疼痛雄性大鼠皮质-丘脑的差异重组

Neurobiology of Pain Pub Date : 2026-01-01 Epub Date: 2025-12-25 DOI: 10.1016/j.ynpai.2025.100206

Aoling Cai , Qing Liu , Wenchang Zhou , Danhao Zheng , Wen Zhang , Xiaodong Liu , Mamatmusayeva Nilufar , Anne Manyande , Feng Gao , Jie Wang , Jun Fang , Xuebi Tian

{"title":"Differential Cortico-Thalamic reorganization in Opioid-Induced hyperalgesia and neuropathic pain male rats","authors":"Aoling Cai , Qing Liu , Wenchang Zhou , Danhao Zheng , Wen Zhang , Xiaodong Liu , Mamatmusayeva Nilufar , Anne Manyande , Feng Gao , Jie Wang , Jun Fang , Xuebi Tian","doi":"10.1016/j.ynpai.2025.100206","DOIUrl":"10.1016/j.ynpai.2025.100206","url":null,"abstract":"<div><div>Both opioid use and peripheral nerve injury can lead to hyperalgesia. Whereas in peripheral nerve injury, the central neuroplastic is secondary to sustained peripheral signaling, opioid-induced hyperalgesia (OIH) involves maladaptive alterations in both the peripheral and central nervous systems. However, the precise neurobiological mechanisms underlying these two distinct forms of hyperalgesia remain incompletely understood. In this study, OIH and spared nerve injury (SNI), a model of peripheral nerve injury, were established in male rats to investigate the similarities and differences in brain activity. Resting-state fMRI and mechanical stimulus task-state fMRI were employed to identify the differential brain regions between those two groups. Both resting-state fMRI and task-state fMRI revealed substantial differences in pain-related functional networks between these two models. Notably, OIH was characterized by a widespread reduction in whole-brain activity, whereas SNI primarily exhibited abnormal activation in specific pain-processing regions. Specifically, enhanced synchrony between the medial parietal association cortex (MPtA) and the ventral posterior thalamic nucleus (VP) was observed in the OIH model, but not in the SNI model. These abnormal changes were further confirmed through <em>in vivo</em> electrophysiological recordings. This study reveals a whole-brain activity responses to resting state and mechanical stimuli in both OIH and SNI models, while also identifying a special thalamo-parietal circuit involved in opioid-induced hyperalgesia. It provides new insights into the neural mechanisms between OIH and SNI, potentially guiding the new strategies for hyperalgesia therapy.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100206"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Females show enhanced susceptibility to develop nerve injury and constant joint pain compared to males in a mouse model of knee joint pain 在小鼠膝关节疼痛模型中，与雄性相比，雌性对神经损伤和持续关节疼痛的易感性增强

Neurobiology of Pain Pub Date : 2026-01-01 Epub Date: 2026-02-06 DOI: 10.1016/j.ynpai.2026.100209

Madison G. Mueth , Abigail Del Greco , Tyler Vesey , Sebastien Sannajust , Victoria Eaton , Peter Caradonna , Talia Lizotte , Kathleen A. Becker , Eliza Grlickova-Duzevik , Benjamin J. Harrison , Tamara King

{"title":"Females show enhanced susceptibility to develop nerve injury and constant joint pain compared to males in a mouse model of knee joint pain","authors":"Madison G. Mueth , Abigail Del Greco , Tyler Vesey , Sebastien Sannajust , Victoria Eaton , Peter Caradonna , Talia Lizotte , Kathleen A. Becker , Eliza Grlickova-Duzevik , Benjamin J. Harrison , Tamara King","doi":"10.1016/j.ynpai.2026.100209","DOIUrl":"10.1016/j.ynpai.2026.100209","url":null,"abstract":"<div><div>Arthritis is a leading cause of diminished quality of life from chronic pain and disability and is more severe in female patients. Arthritis pain is difficult to manage due to its heterogeneous nature. Patients report joint pain during use that dissipates with joint rest, however some patients also report constant joint pain that fails to abate with rest. A murine model of osteoarthritis knee joint pain was used to explore the hypothesis that constant joint pain is associated with increased nerve injury, and females develop constant pain and nerve injury at earlier stages of joint damage compared to males. Monosodium iodoacetate (MIA) was injected into the intra-articular space of the knee joint followed by analysis of weight asymmetry and analgesia-induced conditioned place preference (CPP) 2 weeks later. Knee joints and dorsal root ganglia (DRG) were collected following behavioral analyses to assess joint pathology, changes in innervation, and nerve injury. Females developed analgesia-induced CPP at a 5-fold lower concentration of MIA (16 mg/mL) compared to males (80 mg/mL), while males treated with 16 mg/mL MIA only developed weight asymmetry. Equivalent joint pathology and changes in innervation were observed in males and females treated with 16 mg/mL MIA despite differences in pain-like behaviors. Increased expression of activating transcription factor-3 (ATF3) mRNA, a marker of nerve injury, was only observed in DRG L2-L5 of females and males with analgesia-induced CPP. These observations indicate that females have increased susceptibility to arthritis associated nerve injury that likely contributes to sex differences in joint pain.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100209"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Peripheral immune response and axonal degeneration in the hind paw skin of mice with experimental autoimmune encephalomyelitis 实验性自身免疫性脑脊髓炎小鼠后爪皮肤外周免疫应答和轴突变性

Neurobiology of Pain Pub Date : 2026-01-01 Epub Date: 2025-12-31 DOI: 10.1016/j.ynpai.2025.100207

Andrea G. Klassen , Timothy N. Friedman , Gustavo Tenorio , Jason R. Plemel , Anna M.W. Taylor , Bradley J. Kerr

{"title":"Peripheral immune response and axonal degeneration in the hind paw skin of mice with experimental autoimmune encephalomyelitis","authors":"Andrea G. Klassen , Timothy N. Friedman , Gustavo Tenorio , Jason R. Plemel , Anna M.W. Taylor , Bradley J. Kerr","doi":"10.1016/j.ynpai.2025.100207","DOIUrl":"10.1016/j.ynpai.2025.100207","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is traditionally considered a central nervous system (CNS) disease characterized by chronic inflammation and demyelination in the brain and spinal cord, often resulting in debilitating neuropathic pain. While the primary mechanisms of pain in MS are attributed to central mechanisms, recent evidence suggests that peripheral nervous system (PNS) changes may also contribute. Peripheral neurons in the dorsal root ganglia (DRG), which relay sensory information to the CNS, can undergo inflammation-induced structural and functional changes that amplify pain sensitivity. In human MS and its animal model, experimental autoimmune encephalomyelitis (EAE), inflammation and neuronal injury have been observed in the DRG, yet the role of the PNS in MS pain remains underexplored. To investigate peripheral contributions to pain in EAE, we examined disease-induced changes in hind paw cutaneous tissue and found increased inflammation at disease onset that coincided with tactile hypersensitivity. Intraepidermal nerve fiber (IENF) loss was observed in both sexes at disease onset; however, a sex-specific difference in reinnervation emerged by four weeks post-immunization, with females exhibiting significant reinnervation while males did not. These findings identify sex-dependent patterns of peripheral innervation during EAE and raise the possibility that peripheral mechanisms may contribute differently across sexes.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100207"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Xpro®1595 alleviates neuropathic pain by targeting spinal dorsal horn ADAM17-mediated inflammation Xpro®1595通过靶向脊髓背角adam17介导的炎症减轻神经性疼痛。

Neurobiology of Pain Pub Date : 2026-01-01 Epub Date: 2026-02-12 DOI: 10.1016/j.ynpai.2026.100210

Li Li , Yidie Su , Ling-ling Sun , Wei-Wei Yao , Yan-Yan Sun

{"title":"Xpro®1595 alleviates neuropathic pain by targeting spinal dorsal horn ADAM17-mediated inflammation","authors":"Li Li , Yidie Su , Ling-ling Sun , Wei-Wei Yao , Yan-Yan Sun","doi":"10.1016/j.ynpai.2026.100210","DOIUrl":"10.1016/j.ynpai.2026.100210","url":null,"abstract":"<div><div>A disintegrin and metalloprotease 17 (ADAM17) mediates the shedding of key pro-inflammatory cytokines, yet its specific contribution to neuropathic pain remains elusive. Here, we investigated the role of ADAM17 in the rat spinal nerve ligation (SNL) model. Following nerve injury, ADAM17 expression was significantly upregulated in the spinal dorsal horn (SDH) and dorsal root ganglion (DRG). Specifically, ADAM17 colocalized with TRPV1 and IB4 positive afferents in the superficial SDH, and with IB4, CGRP, and TRPV1 positive neurons in the DRG. Intrathecal administration of exogenous ADAM17 to naive rats recapitulated neuropathic pain behaviors—inducing mechanical and thermal hypersensitivity—and significantly increased the levels of TNF-α, IL-1β, and IL-6 in the SDH. Conversely, therapeutic treatment with Xpro®1595 markedly attenuated SNL-induced pain behaviors. This analgesic effect correlated with the suppression of injury-induced ADAM17 upregulation and a consequent reduction in proinflammatory cytokines. These findings demonstrate that ADAM17 is a critical driver of the neuroinflammatory cascade in neuropathic pain. Moreover, our data suggest that the analgesic efficacy of Xpro®1595 is mediated, at least in part, by disrupting this ADAM17-dependent inflammatory feedback loop.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100210"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Context dependent roles of FGF13B-NaV1.7 interaction in pain signaling FGF13B-NaV1.7相互作用在疼痛信号传导中的上下文依赖作用

Neurobiology of Pain Pub Date : 2026-01-01 Epub Date: 2026-02-04 DOI: 10.1016/j.ynpai.2026.100208

Erick J. Rodríguez-Palma , Samantha Perez-Miller , Kimberly Gomez , Rajesh Khanna

{"title":"Context dependent roles of FGF13B-NaV1.7 interaction in pain signaling","authors":"Erick J. Rodríguez-Palma , Samantha Perez-Miller , Kimberly Gomez , Rajesh Khanna","doi":"10.1016/j.ynpai.2026.100208","DOIUrl":"10.1016/j.ynpai.2026.100208","url":null,"abstract":"<div><div>Voltage-gated sodium channels, such as Na<sub>V</sub>1.7, serve as pivotal regulators of sensory neuron excitability and nociception. While gain- and loss-of-function mutations in <em>SCN9A</em> cause inherited pain syndromes or congenital insensitivity to pain, the functional regulation of Na<sub>V</sub>1.7channels by intracellular protein partners remains incompletely defined. Among these, the fibroblast growth factor 13 isoform B (FGF13B) has emerged as a critical, yet controversial, modulator of Na<sub>V</sub>1.7. FGF13B binds the Na<sub>V</sub>1.7C-terminal domain, but reported consequences of this interaction appear conflicting, with studies describing both suppression and enhancement of channel function and nociceptor excitability. Here, we review recent genetic, electrophysiological, and pharmacology advances and propose that FGF13B functions as a context-dependent regulatory rheostat of Na<sub>V</sub>1.7 rather than as a unidirectional modulator. We highlight how the net functional outcome of this interaction depends on cellular and signaling context and discuss the therapeutic potential of targeting the FGF13B/Na<sub>V</sub>1.7complex in pain conditions.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"19 ","pages":"Article 100208"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NGF stimulation alters the transcriptome and surface TrkB expression in axons of dorsal root ganglion neurons. NGF刺激改变背根神经节神经元轴突的转录组和表面TrkB表达。

Neurobiology of Pain Pub Date : 2025-08-05 eCollection Date: 2025-07-01 DOI: 10.1016/j.ynpai.2025.100194

Maximilian Koch, Manas Kshirsagar, Ankita Rawat, Abdolhossein Zare, Felicitas Schlott, Thorsten Bischler, Panagiota Arampatzi, Michael Briese, Michael Sendtner

{"title":"NGF stimulation alters the transcriptome and surface TrkB expression in axons of dorsal root ganglion neurons.","authors":"Maximilian Koch, Manas Kshirsagar, Ankita Rawat, Abdolhossein Zare, Felicitas Schlott, Thorsten Bischler, Panagiota Arampatzi, Michael Briese, Michael Sendtner","doi":"10.1016/j.ynpai.2025.100194","DOIUrl":"10.1016/j.ynpai.2025.100194","url":null,"abstract":"<p><p>Nerve growth factor (NGF) is released after injury from macrophages and other cell types and induces an inflammatory response in neurons, characterized by local subcellular reactions and transcriptomic modulation. NGF-induced axonal transcriptome modulation may be crucial for pain initiation and maintenance. To explore these acute modulations, we cultured dorsal root ganglion neurons in microfluidic chambers and stimulated the axons with NGF. We found that axonal levels of the <i>Il7</i> transcript encoding interleukin-7 (IL-7) are increased after NGF stimulation, followed by IL-7 release from axons. In growth cones of sensory neurons, we also observed a reorganization of the ribosomal subunits 60S and 40S in response to NGF stimulation. In addition, a dynamic change in the spatio-temporal distribution of the Tropomyosin Kinase B (TrkB) receptor occurs at the plasma membrane of sensory neuron growth cones. TrkB is recruited from the endoplasmic reticulum (ER) leading to increased cell surface levels. De-novo synthesis of TrkB seems to be limited to somatic regions of sensory neurons. Thus, cytosolic mechanisms within distal regions of the sensory neurons may autonomously regulate signaling and translation in response to external NGF stimuli.</p>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"100194"},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12355597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ASIC1a-associated mechanical hypersensitivity in the GlaKO Fabry disease mouse model GlaKO法布里病小鼠模型中asic1a相关的机械超敏反应

Neurobiology of Pain Pub Date : 2025-07-01 Epub Date: 2025-06-26 DOI: 10.1016/j.ynpai.2025.100189

Mayra Micaela Montes , Libia Catalina Salinas Castellanos , Georgina Oriana Mingolo Malnati , Juan Santiago Guidobono , Ariel Félix Gualtieri , Mariela Lacave , Romina De Lucca , María Natalia Gobetto , Pablo Gabriel Vetta , Zaira Soledad Verónica Náguila , Fernanda Toledo , Osvaldo Daniel Uchitel , Carina Weissmann

{"title":"ASIC1a-associated mechanical hypersensitivity in the GlaKO Fabry disease mouse model","authors":"Mayra Micaela Montes , Libia Catalina Salinas Castellanos , Georgina Oriana Mingolo Malnati , Juan Santiago Guidobono , Ariel Félix Gualtieri , Mariela Lacave , Romina De Lucca , María Natalia Gobetto , Pablo Gabriel Vetta , Zaira Soledad Verónica Náguila , Fernanda Toledo , Osvaldo Daniel Uchitel , Carina Weissmann","doi":"10.1016/j.ynpai.2025.100189","DOIUrl":"10.1016/j.ynpai.2025.100189","url":null,"abstract":"<div><div>Different lines of evidence point to a role for Acid-sensing ion channel 1 (ASIC1) in pain perception, acting as sensors in both the central nervous system and peripheral tissues. While elevated ASIC1 protein expression has been documented in various pain conditions, our study focuses on its involvement in the context of Fabry disease (FD).</div><div>Using a mouse model of FD, we observed a significant increase in ASIC1 protein expression in pain-related areas including the anterior cingulate cortex (ACC), as well as the spinal cord (SC) and dorsal root ganglia (DRG) at the lumbar, thoracic, and cervical levels. This upregulation was accompanied by increased ASIC1a mRNA levels and ERK phosphorylation. Moreover, in FD mice, ASIC1 protein expression was found to be modulated by age and sex: it was higher in female mice than in males, and increased with age in both sexes.</div><div>These findings, together with our previous work showing unaltered ASIC1a mRNA levels but microRNA-mediated regulation of ASIC1a protein in the formalin-induced acute pain model, highlight distinct mechanisms of ASIC1a regulation in FD-associated versus acute pain. Additionally, our study revealed heightened mechanical sensitivity in FD mice that could be prevented using a channel blocker, further highlighting the involvement of ASIC1a channels in pain pathways associated with Fabry disease. Our findings suggest that ASIC1a channels may serve as promising therapeutic targets for pain management in Fabry disease.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100189"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The effect of depression on the peak alpha frequency as a biomarker of pain sensitivity 抑郁对作为疼痛敏感性生物标志物的α峰频率的影响

Neurobiology of Pain Pub Date : 2025-07-01 Epub Date: 2025-08-06 DOI: 10.1016/j.ynpai.2025.100193

Mingge Shi , Luiza Bonfim Pacheco , Natalia Egorova-Brumley

{"title":"The effect of depression on the peak alpha frequency as a biomarker of pain sensitivity","authors":"Mingge Shi , Luiza Bonfim Pacheco , Natalia Egorova-Brumley","doi":"10.1016/j.ynpai.2025.100193","DOIUrl":"10.1016/j.ynpai.2025.100193","url":null,"abstract":"<div><h3>Objective</h3><div>To assess how Peak Alpha Frequency (PAF) as a neurophysiological biomarker of pain sensitivity is influenced by conditions often comorbid with chronic pain, e.g., depression, and how methodological differences in deriving PAF, e.g., from Eyes-open (EO) vs. Eyes-closed (EC) EEG recordings affect this association.</div></div><div><h3>Methods</h3><div>We analyzed data from 47 participants (70 % female) aged 18–51 years (<em>M</em> = 25.0, <em>SD</em> = 6.50). Among them, all participants underwent EO EEG recording but only a subset of 25 participants underwent both EO and EC recording. Depression (Patient Health Quotient – 9 M = 4.49, SD = 3.96) and sensitivity to heat pain were measured.</div></div><div><h3>Results</h3><div>In EO, Spearman correlations showed no significant PAF-pain relationship (p = 0.530) but a positive correlation with depression (ρ = 0.348, p = 0.019). In EC, no significant correlations emerged, though a trend (p = 0.052) suggested depression might moderate PAF-pain links. Notably, the EO-EC PAF difference negatively correlated with depression (ρ = −0.54, p < 0.01).</div></div><div><h3>Conclusions</h3><div>PAF may be sensitive to depression, albeit in the opposite direction to pain, and therefore mask the association between PAF and pain in individuals with depression. Differences in EO vs. EC PAF, as well as the EO-EC difference warrant further study.</div></div><div><h3>Significance</h3><div>Depression affects PAF especially in the eyes-open recordings.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100193"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region 一种无毒镇痛药通过靶向PAG脑区引发细胞特异性基因组和表观基因组调节

Neurobiology of Pain Pub Date : 2025-07-01 Epub Date: 2025-07-20 DOI: 10.1016/j.ynpai.2025.100192

Hernan A. Bazan , Brian L. Giles , Surjyadipta Bhattacharjee , Scott Edwards , Nicolas G. Bazan

{"title":"A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region","authors":"Hernan A. Bazan , Brian L. Giles , Surjyadipta Bhattacharjee , Scott Edwards , Nicolas G. Bazan","doi":"10.1016/j.ynpai.2025.100192","DOIUrl":"10.1016/j.ynpai.2025.100192","url":null,"abstract":"<div><div>Acetaminophen (ApAP) is widely used for pain management, but overuse or overdose leads to hepatotoxicity, making it the leading cause of acute liver failure globally. There is an urgent need for safer pain medications, as other non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) are nephrotoxic. We have identified SRP-001 as a safer, non-hepatotoxic, novel analgesic that overcomes ApAP’s limitations by avoiding NAPQI formation and preserving hepatic tight junctions. Using coupled RNA and ATAC sequencing, from the periaqueductal gray (PAG) midbrain region, we compared the genetic and epigenetic signatures of SRP-001 and ApAP treatments following complete Freund’s adjuvant (CFA)-induced inflammatory pain against no treatment and vehicle controls. Our analysis revealed differential activity in three transcription factor families (SOX, SP/KLF, and AP-1) with cell-specific patterns and altered neuron-neuron interactions through neurexin-neuregulin signaling. SRP-001 and ApAP demonstrated similar genetic and epigenetic outcomes, indicating that SRP-001 is a favorable alternative due to its non-hepatotoxic properties while maintaining the same antinociceptive effects as ApAP.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100192"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144694667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0