Bone pain in fibrous dysplasia does not rely on aberrant sensory nerve sprouting or neuroma formation.

IF 5.9 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Biagio Palmisano, Chiara Tavanti, Giorgia Farinacci, Giorgio Gosti, Marco Leonetti, Samantha Donsante, Giuseppe Giannicola, Natasha Appelman-Dijkstra, Alessandro Corsi, Ernesto Ippolito, Mara Riminucci
{"title":"Bone pain in fibrous dysplasia does not rely on aberrant sensory nerve sprouting or neuroma formation.","authors":"Biagio Palmisano, Chiara Tavanti, Giorgia Farinacci, Giorgio Gosti, Marco Leonetti, Samantha Donsante, Giuseppe Giannicola, Natasha Appelman-Dijkstra, Alessandro Corsi, Ernesto Ippolito, Mara Riminucci","doi":"10.1093/jbmr/zjaf066","DOIUrl":null,"url":null,"abstract":"<p><p>Bone pain is a major symptom of many skeletal disorders. Fibrous dysplasia (FD) is a genetic disease with mono or polyostotic skeletal phenotype due to the post-zygotic occurrence of the causative Gsα mutation. Bone pain in FD often associates with skeletal deformities and fractures or nerve impingement by the pathological tissue. However, even in the absence of complications, FD patients often complain of a chronic pain that does not correlate with their disease burden. Multiple hypotheses have been made to explain this pain. However, its pathogenetic mechanisms remain, as yet, largely unexplored. In this study, we first demonstrate that the FD mouse model EF1α-GsαR201C develops behavioral impairments and altered response to nociceptive stimuli that, as in FD patients, do not correlate with their skeletal disease burden, thus providing a reliable model to study bone pain in FD. Then, we show that in EF1α-GsαR201C mice, the overall pattern of skeletal innervation is preserved and that within FD lesions, sensory fibers are variably and focally distributed, mainly at perivascular sites. Finally, we provide the first analysis of a series of human FD bone biopsies showing that, within the lesional tissue, sensory nerve fibers are few despite the rich vascular network and appear to be well-organized. These data show that, albeit sensory nerve fibers are found within FD lesions, bone pain in humans and functional impairment in mice are not associated to pathological sensory nerve sprouting or formation of neuromas in the Gsα-mutated skeleton.</p>","PeriodicalId":185,"journal":{"name":"Journal of Bone and Mineral Research","volume":" ","pages":"999-1014"},"PeriodicalIF":5.9000,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12308826/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Bone and Mineral Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jbmr/zjaf066","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

Abstract

Bone pain is a major symptom of many skeletal disorders. Fibrous dysplasia (FD) is a genetic disease with mono or polyostotic skeletal phenotype due to the post-zygotic occurrence of the causative Gsα mutation. Bone pain in FD often associates with skeletal deformities and fractures or nerve impingement by the pathological tissue. However, even in the absence of complications, FD patients often complain of a chronic pain that does not correlate with their disease burden. Multiple hypotheses have been made to explain this pain. However, its pathogenetic mechanisms remain, as yet, largely unexplored. In this study, we first demonstrate that the FD mouse model EF1α-GsαR201C develops behavioral impairments and altered response to nociceptive stimuli that, as in FD patients, do not correlate with their skeletal disease burden, thus providing a reliable model to study bone pain in FD. Then, we show that in EF1α-GsαR201C mice, the overall pattern of skeletal innervation is preserved and that within FD lesions, sensory fibers are variably and focally distributed, mainly at perivascular sites. Finally, we provide the first analysis of a series of human FD bone biopsies showing that, within the lesional tissue, sensory nerve fibers are few despite the rich vascular network and appear to be well-organized. These data show that, albeit sensory nerve fibers are found within FD lesions, bone pain in humans and functional impairment in mice are not associated to pathological sensory nerve sprouting or formation of neuromas in the Gsα-mutated skeleton.

纤维性发育不良的骨痛不依赖于异常的感觉神经萌芽或神经瘤的形成。
骨痛是许多骨骼疾病的主要症状。纤维发育不良(FD)是一种遗传性疾病,具有单骨或多骨表型,由于受精卵后发生的致病gsa α突变。FD的骨痛常与病理组织的骨骼畸形、骨折或神经撞击有关。然而,即使在没有并发症的情况下,FD患者也经常抱怨慢性疼痛,这与他们的疾病负担无关。人们提出了多种假设来解释这种疼痛。然而,它的发病机制仍然是,到目前为止,很大程度上未被探索。在这项研究中,我们首先证明FD小鼠模型EF1α-GsαR201C出现行为障碍和对伤害性刺激的反应改变,与FD患者一样,与他们的骨骼疾病负担无关,从而为FD研究骨骼疼痛提供了可靠的模型。然后,我们发现在EF1α-GsαR201C小鼠中,骨骼神经支配的整体模式被保留,并且在FD病变内,感觉纤维是可变和局部分布的,主要分布在血管周围。最后,我们提供了一系列人类FD骨活检的首次分析,表明在病变组织中,尽管血管网络丰富,但感觉神经纤维很少,并且看起来组织良好。这些数据表明,尽管在FD病变中发现了感觉神经纤维,但在gs α-突变的骨骼中,人类的骨痛和小鼠的功能损伤与病理性感觉神经萌芽或神经瘤的形成无关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Journal of Bone and Mineral Research
Journal of Bone and Mineral Research 医学-内分泌学与代谢
CiteScore
11.30
自引率
6.50%
发文量
257
审稿时长
2 months
期刊介绍: The Journal of Bone and Mineral Research (JBMR) publishes highly impactful original manuscripts, reviews, and special articles on basic, translational and clinical investigations relevant to the musculoskeletal system and mineral metabolism. Specifically, the journal is interested in original research on the biology and physiology of skeletal tissues, interdisciplinary research spanning the musculoskeletal and other systems, including but not limited to immunology, hematology, energy metabolism, cancer biology, and neurology, and systems biology topics using large scale “-omics” approaches. The journal welcomes clinical research on the pathophysiology, treatment and prevention of osteoporosis and fractures, as well as sarcopenia, disorders of bone and mineral metabolism, and rare or genetically determined bone diseases.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信