Neurobiology of Pain最新文献

{"title":"ASIC1a-associated mechanical hypersensitivity in the GlaKO Fabry disease mouse model","authors":"Mayra Micaela Montes ,&nbsp;Libia Catalina Salinas Castellanos ,&nbsp;Georgina Oriana Mingolo Malnati ,&nbsp;Juan Santiago Guidobono ,&nbsp;Ariel Félix Gualtieri ,&nbsp;Mariela Lacave ,&nbsp;Romina De Lucca ,&nbsp;María Natalia Gobetto ,&nbsp;Pablo Gabriel Vetta ,&nbsp;Zaira Soledad Verónica Náguila ,&nbsp;Fernanda Toledo ,&nbsp;Osvaldo Daniel Uchitel ,&nbsp;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}

{"title":"A non-toxic analgesic elicits cell-specific genomic and epigenomic modulation by targeting the PAG brain region","authors":"Hernan A. Bazan ,&nbsp;Brian L. Giles ,&nbsp;Surjyadipta Bhattacharjee ,&nbsp;Scott Edwards ,&nbsp;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}

{"title":"Neuronal physiology of amygdala neurons in the context of injury and pain","authors":"Blesson K Paul,&nbsp;Maria Isabel Nunez-Ordaz,&nbsp;Joseph R. Samuel,&nbsp;Benedict J. Kolber","doi":"10.1016/j.ynpai.2025.100190","DOIUrl":"10.1016/j.ynpai.2025.100190","url":null,"abstract":"<div><div>The amygdala integrates polymodal information including nociceptive stimuli. It is implicated as a key node in regulating both sensory-discriminative and emotional-affective aspects of pain and central sensitization. While central sensitization mechanisms in persistent pain are not completely understood, studying the neuronal properties exhibited by the amygdala neurons within their functional context, in this case, nociception, is important. Such studies can shed light on the behavior-modulating potential of the amygdala. In the last twenty years, multiple laboratories have begun the process of dissecting the cell-type specific activity involved in amygdala function. This review surveys these electrophysiological properties of neurons from different amygdala nuclei, cell types and circuitry studied so far, in the context of nociception and injury. A population-level accounting of these cell types provides greater insight into identifying specific targets to develop interventions for pain-mediated affective conditions.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100190"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563031","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":"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":"2025-06-18","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":"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":"2025-05-22","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":"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":"2025-05-16","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":"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":"2025-05-08","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":"Humanized NaV1.8 rats overcome cross-species potency shifts in developing novel NaV1.8 inhibitors","authors":"Dillon S. McDevitt ,&nbsp;Joshua D. Vardigan ,&nbsp;Xiaoping Zhou ,&nbsp;Thomas W. Rosahl ,&nbsp;Heather Zhou ,&nbsp;Eric A. Price ,&nbsp;Michelle K. Clements ,&nbsp;Yuxing Li ,&nbsp;Nissi Varghese ,&nbsp;Alicja Krasowska-Zoladek ,&nbsp;Shawn J. Stachel ,&nbsp;Michael J. Breslin ,&nbsp;Christopher S. Burgey ,&nbsp;Richard L. Kraus ,&nbsp;Parul S. Pall ,&nbsp;Darrell A. Henze ,&nbsp;Vincent P. Santarelli","doi":"10.1016/j.ynpai.2025.100182","DOIUrl":"10.1016/j.ynpai.2025.100182","url":null,"abstract":"<div><div>Voltage-gated sodium channel isoform 1.8 (Na_V1.8) has emerged as a promising pharmaceutical target for the treatment of acute and chronic pain. However, highly selective and potent inhibitors for this channel have been difficult to develop and only recently have advanced to clinical testing. Our efforts to develop Na_V1.8 small molecule inhibitors yielded a series of molecules with favorable <em>in vitro</em> potency and selectivity against the human Na_V1.8 channel but exhibited dramatic rightward potency shifts against the rodent channel, severely limiting <em>in vivo</em> screening and candidate selection. In anticipation of supporting drug discovery efforts, a transgenic rat line expressing the human Na_V1.8 channel in lieu of the rodent channel was developed. Utilizing these humanized animals, the <em>in vitro</em> potency of our chemical matter in freshly isolated humanized rat DRG neurons was consistent with <em>in vitro</em> human potency values, enabling <em>in vivo</em> work to progress. We demonstrate capsaicin-induced nocifensive behaviors (CNB) as a moderate throughput <em>in vivo</em> screening assay, from which we demonstrate pharmacokinetic-pharmacodynamic (PK-PD) and <em>in vitro</em>-<em>in vivo</em> correlation (IVIVC) relationships. We identified MSD199 as a potent Na_V1.8 inhibitor with acute pain efficacy and assessed it in traditional inflammatory (Complete Freund’s Adjuvant) and neuropathic (spinal nerve ligation) behavioral chronic pain assays where it was shown to significantly reduce pain-related behaviors. Overall, we demonstrate the utility of humanized transgenic animals when cross-species potency shifts are observed within an otherwise promising chemical series.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100182"},"PeriodicalIF":0.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143682473","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":"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":"2025-02-28","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}