Biagio Palmisano, Chiara Tavanti, Giorgia Farinacci, Giorgio Gosti, Marco Leonetti, Samantha Donsante, Giuseppe Giannicola, Natasha Appelman-Dijkstra, Alessandro Corsi, Ernesto Ippolito, Mara Riminucci
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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.
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.