Neurobiology of Pain最新文献

{"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}

{"title":"Voluntary exercise prevents and eradicates anxiety-like behavior by influencing parvalbumin-positive neurons, perineuronal nets, and microglia activation in corticolimbic regions of neuropathic pain rats","authors":"Thu Nguyen Dang ,&nbsp;Cuong Nguyen Van ,&nbsp;Ryosuke Ochi ,&nbsp;Hiroki Kuwamura ,&nbsp;Tomoyuki Kurose ,&nbsp;Yoki Nakamura ,&nbsp;Kazue Hisaoka-Nakashima ,&nbsp;Norimitsu Morioka ,&nbsp;Hisao Nishijo ,&nbsp;Naoto Fujita ,&nbsp;Susumu Urakawa","doi":"10.1016/j.ynpai.2025.100181","DOIUrl":"10.1016/j.ynpai.2025.100181","url":null,"abstract":"<div><div>Anxiety-like behavior often emerges in the later stages of neuropathic pain, exacerbating the pain condition and potentially involving parvalbumin-positive (PV⁺) neurons. This study aimed to investigate the effects of voluntary exercise on neuropathic pain-induced anxiety and its relationship with PV⁺ neurons, perineuronal nets (PNNs, labeled with Wisteria floribunda agglutinin [WFA]), and microglia in the corticolimbic regions. Male Wistar rats with partial sciatic nerve ligation (PSL) were given access to running wheels either from 3 days (early voluntary exercise [EEx]) or from 4 weeks (late voluntary exercise [LEx]) postoperatively. Nociceptive behaviors were assessed using the von Frey and acetone tests, while anxiety-like behaviors were assessed using the open field and elevated plus maze tests. Brain sections were histologically analyzed using immunohistochemistry and immunofluorescence 8 weeks post-surgery. Both early and late exercise partially restored the paw withdrawal thresholds and the arousal response. PSL-EEx rats did not exhibit anxiety-like behaviors. PSL-LEx rats transiently showed anxiety-like behaviors, but these were eradicated by exercise. PSL altered PV⁺ neurons and PNNs in specific corticolimbic subregions. Notably, voluntary exercise restored the densities of PV⁺-strong WFA⁺ neurons in the basolateral amygdala, PV⁺-WFA^-, and PV⁺-WFA⁺ neurons in the anterior cingulate cortex, and PV⁺-WFA⁺ neurons in the hippocampal cornu ammonis 1. These changes correlated with reduced anxiety-like behaviors. Exercise modulated PSL-induced microglial activation and interacted differently with these neurons. These findings suggest that voluntary exercise prevents and eliminates chronic pain-induced anxiety through neuronal mechanisms other than analgesic effects, potentially involving PV⁺ neurons, PNNs, and microglia in the corticolimbic subregions.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"18 ","pages":"Article 100181"},"PeriodicalIF":0.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143601363","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":"The contribution of clock genes BMAL1 and PER2 in osteoarthritis-associated pain","authors":"Erick J. Rodríguez-Palma ,&nbsp;Santiago Loya-Lopez ,&nbsp;Kyle Allen ,&nbsp;Yenisel Cruz-Almeida ,&nbsp;Rajesh Khanna","doi":"10.1016/j.ynpai.2024.100177","DOIUrl":"10.1016/j.ynpai.2024.100177","url":null,"abstract":"<div><div>Joint pain is the primary symptom of osteoarthritis (OA) and the main motivator for patients to seek medical care. OA-related pain significantly restricts joint function and diminishes quality of life. Despite the availability of various pain-relieving medications for OA, current treatment strategies often fall short in delivering adequate pain relief. Furthermore, long-term use of pain medications for OA management is frequently linked with notable side effects and toxicities, suggesting the need to explore new potential targets to treat pain in OA patients. In this context, clock genes, particularly brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) and period circadian protein homolog 2 (PER2), known for their role in circadian rhythms, represent promising opportunities for pharmacological interventions due to their involvement in both the development and maintenance of OA pain. While BMAL1 and PER2 have been extensively studied in neuropathic and inflammatory pain, their specific contributions to OA pain remain less clear, demanding further investigation. This narrative review aims to synthesize the relationship between OA pain and the BMAL1 and PER2 signaling pathways, ultimately exploring the potential therapeutic role of clock genes in addressing this challenging condition.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"17 ","pages":"Article 100177"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030301","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":"Glial activation and nociceptive neuropeptide elevation associated with the development of chronic post-traumatic headache following repetitive blast exposure","authors":"Amirah Wright ,&nbsp;Susan F. Murphy ,&nbsp;Pamela J. VandeVord","doi":"10.1016/j.ynpai.2024.100178","DOIUrl":"10.1016/j.ynpai.2024.100178","url":null,"abstract":"<div><div>Chronic headaches and pain are prevalent in those who are exposure to blast events, yet there is a gap in fundamental data that identifies the pathological mechanism for the chronification of pain. Blast-related post-traumatic headaches (PTH) are understudied and chronic pain behaviors in preclinical models can be vital to help elucidate PTH mechanisms. The descending pain modulatory system controls pain perception and involves<!--> <!-->specific brain regions such as the cortex, thalamus, pons, and medulla. In this study, male rats were exposed to repeated blast events to induce traumatic brain injury (bTBI) and subsequently assessed for the development of PTH by testing for chronic pain behaviors and examining the neuropathology of the descending pain pathway. The results demonstrated that facial hypersensitivity developed as early as week two following bTBI and persisted throughout the study (12 weeks). Depressive-like behaviors were observed at 12 weeks following bTBI, and these behaviors were associated with neuropathologies such as microglia ramification and neuropeptide elevation (Calcitonin Gene-Related Peptide, CGRP; Substance P, SP). Overall, these findings support the hypothesis that bTBI causes the activation of microglia and elevation of neuropeptides, which contribute to the development of chronic PTH behaviors.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"17 ","pages":"Article 100178"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754688/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030299","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":"Critical reflections on medication overuse headache in patients with migraine: An unsolved riddle in nociception","authors":"Alberto Chiarugi ,&nbsp;Daniela Buonvicino","doi":"10.1016/j.ynpai.2025.100179","DOIUrl":"10.1016/j.ynpai.2025.100179","url":null,"abstract":"<div><div>Migraine chronification very frequently exposes patients to the inevitable risk of excessive symptomatic intake that, in turn, prompts development of medication overuse headache (MOH). The latter further compromises headache severity establishing a vicious cycle of symptomatic intake and relapsing head pain that critically worsens the overall clinical status of patients. A great deal of attention has been focused on MOH pathogenesis, and thanks to preclinical and clinical studies knowledge about this disorder is now remarkably advanced. Still, some open questions remain regarding issues related to the neurobiology and neurochemistry underpinning pain chronification in MOH patients, as well as the remedies capable of interrupting pronociceptive cephalic sensitization and drug overuse. Here, a critical reappraisal of these issues is provided in an attempt to gain deeper insight and promote debate on a pain disorder that still represents a conundrum in the field of nociception.</div></div>","PeriodicalId":52177,"journal":{"name":"Neurobiology of Pain","volume":"17 ","pages":"Article 100179"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427655","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}