Neurobiology of Pain最新文献

{"title":"Cerebral peak alpha frequency: Associations with chronic pain onset and pain modulation","authors":"Felicitas A. Huber ,&nbsp;Parker A. Kell ,&nbsp;Joanna O. Shadlow ,&nbsp;Jamie L. Rhudy","doi":"10.1016/j.ynpai.2025.100180","DOIUrl":"10.1016/j.ynpai.2025.100180","url":null,"abstract":"<div><div>Chronic pain is highly prevalent in the U.S. and leads to myriad negative sequalae and suffering. One way to address chronic pain is to identify who is at risk and intervene prior to symptom onset. Research suggests resting peak alpha frequency (PAF), the speed of alpha oscillations at rest, is slower in healthy individuals with greater pain sensitivity and in chronic pain patients. Thus, slower PAF may denote chronic pain vulnerability. Other research has shown that individuals at higher risk of chronic pain exhibit disrupted pain modulation, i.e., less efficient pain inhibition and increased pain facilitation. Currently, the ability of PAF to predict chronic pain and its relation to pain modulation is under-researched. This investigation aimed to address this gap by characterizing associations between PAF, onset of chronic pain, and pain modulation. Using archival data from three independent studies, this investigation assessed whether slower PAF is associated with prospectively-determined chronic pain onset, decreased pain inhibition (i.e., impaired conditioned pain modulation, impaired erotica-induced pain inhibition), and increased pain facilitation (i.e., increased temporal summation of pain, augmented mutilation-induced pain facilitation). Results show that slower PAF was associated with greater facilitation of spinal (i.e., nociceptive flexion reflex) and supraspinal (i.e., N2 potential) nociception in response to unpleasant pictures (i.e., human injury images). This suggests that slower PAF is associated with threat-enhanced spinal and supraspinal nociception and may be relevant for chronic pain conditions with disrupted threat systems. Slower PAF was not associated with any other pain outcome, including prospectively determined chronic pain onset. However, chronic pain onset could only be assessed in one study with a mixed eyes open/eyes closed recording, limiting the significance of this finding.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100180"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143548952","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}

{"title":"Patient phenotyping for molecular profiling of neck and low back pain – Study protocol","authors":"Michele Curatolo ,&nbsp;Cathryn Payne ,&nbsp;Abby P. Chiu ,&nbsp;Nguyen T. Tran ,&nbsp;Natalie Yap ,&nbsp;Christoph P. Hofstetter ,&nbsp;Joseph B. Lesnak ,&nbsp;Asta Arendt-Tranholm ,&nbsp;Theodore J. Price ,&nbsp;Jeffrey G. Jarvik ,&nbsp;Judith A. Turner","doi":"10.1016/j.ynpai.2025.100186","DOIUrl":"10.1016/j.ynpai.2025.100186","url":null,"abstract":"<div><h3>Background</h3><div>Chronic neck and low back pain are highly prevalent, leading causes of disability, and associated with long-term opioid use. The development of effective therapeutics is hampered by the limited understanding of the molecular mechanisms underlying these conditions. The Human Nociceptor and Spinal Cord Molecular Signature Center is a consortium within the NIH PRECISION Human Pain Network. The Center aims to fundamentally advance the understanding of the molecular neurobiology and neuroimmunology underlying human neck and low back pain, thereby enabling the discovery of therapeutic targets. We are pursuing this aim by applying bulk, single cell and spatial transcriptomics to tissues recovered from patients with neck and low back pain undergoing C1-2 and lumbar arthrodesis. The C2 dorsal root ganglion, facet joints, muscles, fascia, and intervertebral discs are harvested; control tissues are obtained from organ donors. A critical advantage of human research is the study of molecular neurobiological mechanisms in the context of the phenotypic complexity of chronic pain. The aim of this article is to summarize the rationale and methods used in our project to phenotype patients.</div></div><div><h3>Methods</h3><div>Phenotyping domains include pain-related characteristics such as pain intensity, duration, and location; physical function; psychosocial function; neuropathic components assessed by self-report and quantitative sensory testing; somatosensory functions such as mechanical pain sensitivity and temporal summation; and radiological findings.</div></div><div><h3>Conclusion</h3><div>We anticipate that comprehensive phenotyping will greatly facilitate the identification of phenotype-specific transcriptional signatures associated with chronic neck and low back pain, revealing new neurobiological and/or neuro-immunological mechanisms of painful diseases.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100186"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144124077","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}

{"title":"Unveiling the peripheral nerve hallmarks of chemotherapy-induced neuropathy: insights from paclitaxel treatment in a murine model","authors":"Maria Maiarù ,&nbsp;Andrea Petrini ,&nbsp;Federica De Angelis ,&nbsp;Francesca Nazio ,&nbsp;Sara Marinelli","doi":"10.1016/j.ynpai.2025.100200","DOIUrl":"10.1016/j.ynpai.2025.100200","url":null,"abstract":"<div><div>Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and debilitating side effect of anticancer drugs like paclitaxel, significantly reducing the quality of life for cancer patients. Paclitaxel-induced peripheral neuropathy (PIPN) is primarily characterized by sensory disturbances such as mechanical allodynia and thermal hyperalgesia. Despite its prevalence, the mechanisms driving PIPN are not fully understood, and current treatment options remain limited. This study explores the impact of varying doses of paclitaxel on neuropathic pain, nerve structural changes, and metabolic alterations in a mouse model. Behavioural assessments demonstrated that paclitaxel induced dose-dependent mechanical allodynia and thermal hyperalgesia, with prolonged symptoms at higher doses. Furthermore, sciatic nerve dysfunction was observed, while metabolic tests revealed significant disruptions in glucose and triglyceride levels, suggesting a link between metabolic imbalances and neuropathy. Histological and molecular analyses identified increased TRPV1 and CGRP expression in skin nerve fibers, accompanied by Schwann cell dysfunction, characterized by myelin disorganization, decreased levels of myelin proteins (P0, MBP), and elevated LC3 levels, pointing to autophagy involvement. Moreover, infiltration of macrophages and mast cells into sciatic nerves indicated an innate immune response. These results emphasize the complex nature of PIPN, which involves sensory nerve sensitization, Schwann cell damage, and metabolic dysregulation. Elucidating these pathways could inform the development of more effective therapies aimed at preventing or alleviating the impact of CIPN.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100200"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145332498","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}

{"title":"Left nucleus accumbens volume is associated with poor sleep in hip osteoarthritis","authors":"Natalia Egorova-Brumley ,&nbsp;Luiza Bonfim Pacheco ,&nbsp;Gabby Knox ,&nbsp;Leila Nategh ,&nbsp;Fiona Dobson ,&nbsp;Michelle Hall","doi":"10.1016/j.ynpai.2025.100203","DOIUrl":"10.1016/j.ynpai.2025.100203","url":null,"abstract":"<div><h3>Objective</h3><div>Reduction in the volume of the nucleus accumbens (NAc) has emerged as a promising signature of chronic pain transition, including in osteoarthritis (OA). Yet, less is known about the factors that could influence these changes in the mesolimbic system. Given that poor sleep is common in OA, and recent studies of sleep disturbance on pain perception in animals and healthy populations have specifically implicated the NAc, we hypothesised that the left NAc volume in hip OA would be associated with sleep quality and quantity. Furthermore, we explored how sex interacts with this relationship.</div></div><div><h3>Methods</h3><div>Cross-sectional study in participants with hip OA (n = 34; aged 60+/-12 years, 67 % females) who reported moderate pain were recruited.</div></div><div><h3>Results</h3><div>A one-sample <em>t</em>-test showed that the left NAc volumes were significantly lower than normative values (t = -2.7368, df = 33, p-value = 0.009). In a model (F(4, 29) = 6.642, p &lt; 0.001, R2 = 0.4781) including the total intracranial volume (TIV), sex and age, the left NAc volume was significantly predicted by sleep quality (t = -3.416, p = 0.002) assessed with Pittsburgh Sleep Quality Index (PSQI). Sleep efficiency (t = 2.362, p = 0.025) but not hours spent in bed (p &gt; 0.05) was also a significant predictor. With models exploring sleep*sex interactions, only sleep efficiency demonstrated an interaction, suggesting that the left NAc volume is lower in females with worse sleep efficiency (t = -2.086, p = 0.046, albeit not significant when corrected for multiple comparisons, pFDR = 0.138.)</div></div><div><h3>Conclusions</h3><div>Our results suggest that the reduction of the NAc volumes as a candidate biomarker of pain might be influenced by sleep. This exploratory finding in a chronic hip OA population is consistent with the results previously only reported in animal and experimental pain/sleep studies in healthy participants.</div></div><div><h3>Significance</h3><div>The left NAc as a candidate biomarker of chronic pain is sensitive to the effects of sleep quality, especially in females with OA.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100203"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571069","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}

{"title":"Enhanced trafficking of an inherited erythromelalgia NaV1.7 mutant channel at a physiological temperature","authors":"Malgorzata A. Mis ,&nbsp;Sidharth Tyagi ,&nbsp;Elizabeth J. Akin ,&nbsp;Mohammad-Reza Ghovanloo ,&nbsp;Peng Zhao ,&nbsp;Fadia Dib-Hajj ,&nbsp;Andrew D. Randall ,&nbsp;Stephen G. Waxman ,&nbsp;Sulayman D. Dib-Hajj","doi":"10.1016/j.ynpai.2025.100188","DOIUrl":"10.1016/j.ynpai.2025.100188","url":null,"abstract":"<div><div>Gain-of-function mutations which enhance activation of Na_V1.7, a widely expressed sodium channel in nociceptors, cause human pain disorders including inherited erythromelalgia (IEM). IEM is characterized by attacks of burning pain in distal extremities triggered by warmth, with cooling of affected limbs providing temporary relief. We investigated the behaviour of the IEM-linked L858F mutant Na_V1.7 channel at physiological normal skin temperature (NST, 33–35 °C) in IB4-negative DRG sensory neurons known to include thermosensors. Using voltage-clamp recordings at NST we found that the Na_V1.7-L858F mutant channel shows the characteristic hyperpolarizing shift in activation as has been previously found in recordings at room temperature, and that the current density of the L858F channels is significantly larger than that of WT channels. Using a live-cell optical pulse-chase imaging methodology at NST we observed that accelerated forward-trafficking significantly increases membrane insertion of mutant channels in IB4^- neurons. Current-clamp recordings at NST show increased firing of IB4^- neurons that express the L858F mutant channel, consistent with increased trafficking of the channel at this physiological temperature. Our findings identify enhanced trafficking and membrane insertion of the L858F mutant channels at normal skin temperature in IB4^- neurons as an additional mechanism underlying IEM-related neuronal hyperexcitability.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100188"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144322280","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}

{"title":"Glutamate levels in the cingulate cortex are associated with objective markers of pain sensitivity by way of pre-stimulus alpha band oscillations","authors":"Paulina S. Scheuren ,&nbsp;Oscar Ortiz ,&nbsp;Lukas D. Linde ,&nbsp;Cassandra M. Choles ,&nbsp;Erin L. MacMillan ,&nbsp;John L.K. Kramer","doi":"10.1016/j.ynpai.2025.100204","DOIUrl":"10.1016/j.ynpai.2025.100204","url":null,"abstract":"<div><div>Pain varies substantially from one individual to the next. Understanding the role of brain function in variations to pain, both in health and disease, represents an important steppingstone towards individualized pain management. This study aimed to investigate the association between glutamate levels and pain sensitivity, and whether this is mediated by alpha band oscillations. Fifty-one healthy individuals were recruited for this study. Laser evoked potentials (LEPs) and pain ratings were recorded in response to 20 stimuli applied at 4 different intensities (2.75, 3, 3.25, 3.5 J) to the right volar forearm. Brain alpha band oscillations (7–13 Hz) were extracted from the pre-stimulus timeframe (−1000 ms to −100 ms). Single-voxel magnetic resonance spectroscopy data were collected to estimate regional differences in glutamate levels across the anterior (ACC) and posterior cingulate cortex (PCC) using a 3 T scanner. Cluster analysis of LEPs revealed two clusters (high vs. low N2P2 amplitudes). Glutamate levels were reduced in the PCC versus ACC in the ‘low LEP’ (t = 3.6, p &lt; 0.001), but not ‘high LEP’ cluster (t = 1.08, p = 0.285). Causal mediation analysis revealed that the effect of ACC:PCC glutamate ratio on LEP peak-to-peak amplitudes was mediated via pre-stimulus alpha band oscillations (β_indirect = −25.6(−63.9, −2.4), p = 0.034]. This study indicates that glutamate levels across the cingulate cortexshape subsequent brain responses to noxious input, and that this is mediated by pre-stimulus alpha band oscillations. Both brain metabolites and oscillations thus likely play a vital role in individual variabilities in experimental pain.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100204"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145623295","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}

{"title":"The RNA-binding protein CELF4 is a negative regulator of sensory neuron excitability and mechanical and heat behavioral sensitivity","authors":"Madison G. Mueth ,&nbsp;Peter Neufeld ,&nbsp;Merilla Michael ,&nbsp;Aidan McGrath-Conwell ,&nbsp;Eliza Grlickova-Duzevik ,&nbsp;Tamara King ,&nbsp;Christoph Straub ,&nbsp;Benjamin J. Harrison","doi":"10.1016/j.ynpai.2025.100184","DOIUrl":"10.1016/j.ynpai.2025.100184","url":null,"abstract":"<div><div>RNA-binding proteins (RBPs) regulate gene function by controlling RNA processing, transport, stability, and translation. Recent mechanistic and pre-clinical studies demonstrate that nociceptive sensitivity and plasticity are regulated by RNA-protein interactions. Investigating RBP function in sensory neurons may reveal new strategies to modulate nociceptor excitability and/or sensitivity and improve our understanding of mechanisms that contribute to pain chronification. We previously identified the RBP CUG triplet repeat binding protein (<u>C</u>UGBP) embryonic lethal abnormal vision (<u>E</u>lav)-<u>l</u>ike <u>f</u>amily member <u>4</u> (CELF4) as co-expressed with nociceptive markers in mouse, rat, and macaque dorsal root ganglia (DRG). In the central nervous system, CELF4 limits the translation of synaptic mRNAs, and loss of CELF4 results in hyperexcitability of excitatory neurons and spontaneous seizures. To elucidate the function of CELF4 in sensory neurons, we employed conditional knockout (KO) mouse models, with <em>Celf4</em> deleted selectively in populations of adult DRG neurons. Using patch-clamp electrophysiology in acutely dissociated neurons, we observed a striking reduction in rheobase and hyperexcitability of capsaicin-sensitive adult <em>Celf4</em> KO DRG neurons compared to controls. Behavioral assessments revealed that these mice display robust mechanical and thermal hypersensitivity and an exaggerated evoked hypersensitivity response to intraplantar capsaicin and nerve growth factor. These studies reveal that the translational regulator CELF4 is a powerful negative regulator of sensory neuron excitability and sensory thresholds to heat and mechanical stimuli resulting in thermal and mechanical hypersensitivity in uninjured mice and exacerbating hypersensitivity in injured mice. These findings elucidate a novel mechanism for modulating sensory neuron excitability with high specificity to putative nociceptors.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100184"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143928805","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}

{"title":"Circulating microRNAs differentiate nociceptive and nociplastic pain: An exploratory study","authors":"Hiroyuki Nishie ,&nbsp;Hideki Nakatsuka ,&nbsp;Kazunori Iwasa ,&nbsp;Yuka Sakuta ,&nbsp;Yuichiro Toda ,&nbsp;Shigeru Mitani ,&nbsp;Takeshi Nagasaka","doi":"10.1016/j.ynpai.2025.100191","DOIUrl":"10.1016/j.ynpai.2025.100191","url":null,"abstract":"<div><h3>Background</h3><div>Nociceptive and nociplastic pain arise from distinct biological mechanisms, yet their differentiation remains clinically challenging. Circulating microRNAs (miRNAs) are promising candidates for objective, mechanism-based pain classification.</div></div><div><h3>Objective</h3><div>To explore whether specific circulating miRNAs can differentiate nociceptive pain in patients with hip osteoarthritis (HO) from nociplastic pain in patients with chronic primary pain (CPP), and to assess their relationship with clinical and psychological outcomes.</div></div><div><h3>Methods</h3><div>In this exploratory, single-center study, plasma samples were collected from patients with HO (n = 13), CPP (n = 11), and healthy controls (n = 7). Microarray screening identified candidate miRNAs, which were validated via real-time PCR. Pain intensity (NRS), disability (PDAS), quality of life (EQ-5D), and psychological factors (PCS, PSEQ, TSK-11, PHQ-9) were assessed. Classification accuracy was evaluated using decision tree modeling and ROC analysis.</div></div><div><h3>Results</h3><div><em>Let-7a</em>, <em>miR-26a</em>, and <em>miR-16</em> showed distinct expression profiles and contributed to a predictive model with strong performance (<em>R²</em> = 0.677; AUC &gt; 0.94). <em>Let-7a</em> expression was associated with structural joint changes in HO but not subjective pain ratings. <em>MiR-26a</em> correlated with cognitive-affective pain traits in CPP, and <em>miR-16</em> decreased following CBT, suggesting a role in treatment-related neuroplasticity. <em>MiR-126</em> and <em>miR-146a</em> were linked to reductions in pain intensity post-surgery in the HO group. QOL improved in HO, while psychological factors remained prominent in CPP.</div></div><div><h3>Conclusions</h3><div>This pilot study suggests that circulating miRNAs may aid in differentiating nociceptive and nociplastic pain mechanisms and tracking treatment effects. While preliminary, these findings support the potential utility of miRNA-based biomarkers in precision pain diagnostics and personalized management strategies.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100191"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144587520","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}

{"title":"R and S enantiomers of CBD3063, a CaV2.2 N-type calcium channel modulator, alleviate capsaicin-induced inflammatory pain","authors":"Santiago Loya-López ,&nbsp;Erick J. Rodríguez-Palma ,&nbsp;Aida Calderón-Rivera ,&nbsp;Kimberly Gomez ,&nbsp;Samantha Perez-Miller ,&nbsp;Rajesh Khanna","doi":"10.1016/j.ynpai.2025.100185","DOIUrl":"10.1016/j.ynpai.2025.100185","url":null,"abstract":"<div><div>N-type voltage-gated calcium channels (Ca_V2.2) play a pivotal role in pain signaling, rendering them promising targets for pain treatment. However, direct blockers of Ca_V2.2 have demonstrated limited efficacy due to adverse side effects and inadequate blood–brain barrier penetration. In previous work, we developed CBD3063, a small molecule peptidomimetic that disrupts the Ca_V2.2-CRMP2 (collapsin response mediator protein 2) interaction, resulting in a reduction of Ca_V2.2 currents and pain relief without side effects. In this study, we investigated the individual contributions of the (R) and (S) enantiomers of CBD3063 to its pharmacological effects. Whole-cell patch-clamp recordings from mouse dorsal root ganglion (DRG) sensory neurons indicated that the (S) and (R) enantiomers reduced Ca_V2.2 currents. Furthermore, racemic CBD3063 and the (S) enantiomer exhibited antinociceptive effects in the capsaicin-induced model of inflammatory pain. These findings suggest that the (S) and (R) enantiomers contribute to the therapeutic effects of CBD3063.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100185"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144071751","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}

{"title":"FL/FLT3 signaling enhances mechanical pain hypersensitivity through Interleukin-1 beta (IL-1β) in male mice","authors":"Corinne Sonrier ,&nbsp;Chamroen Sar ,&nbsp;Ivo Melo ,&nbsp;Lucie Dioufoulet ,&nbsp;Gabriel V. Lucena-Silva ,&nbsp;Sylvie Mallié ,&nbsp;Juliette Bertin ,&nbsp;Jean-Philippe Leyris ,&nbsp;Fabrice Ango ,&nbsp;Thiago M. Cunha ,&nbsp;Hamid Moha ou Maati ,&nbsp;Jean Valmier ,&nbsp;Cyril Rivat ,&nbsp;Ilana Méchaly","doi":"10.1016/j.ynpai.2025.100202","DOIUrl":"10.1016/j.ynpai.2025.100202","url":null,"abstract":"<div><div>Fms-like tyrosine kinase 3 (FLT3) plays a critical role in chronic pain through its ligand FL, a cytokine that triggers mechanical pain hypersensitivity. However, the underlying molecular mechanisms remain unclear. Here, we investigate the potential interplay between FL and IL-1β a key cytokine in DRG neurons sensitization and mechanical hyperalgesia through both <em>in vitro</em> and <em>in vivo</em> approaches. ELISA assays reveal that intrathecal FL administration significantly increases IL-1β protein levels in both the DRG and dorsal spinal cord of mice, by four hours post-injection. Using video microscopy and [Ca²⁺] ₁ fluorescence imaging in primary DRG neuron cultures, we demonstrate that FL potentiation of TRPV1 receptor responses to capsaicin is partially mediated by IL-1β signalling, as evidenced by a significant reduction in this potentiation in the presence of the IL-1 receptor antagonist, IL-1Ra. Furthermore, FLT3-driven acute mechanical pain hypersensitivity <em>in vivo</em> is reduced both by prior administration of IL-1Ra and in IL-1 receptor knockout mice. Importantly, IL-1β-induced mechanical pain hypersensitivity remains independent of FLT3 signalling as shown in <em>Flt3</em> knockout mice. Collectively our findings expand the understanding of neuro-immune interactions by demonstrating a potential functional link between FL/FLT3 and IL-1β/IL-1R signalling in nociceptive processing.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100202"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145473642","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}