109: Blocking Nerve Growth Factor Attenuates Nociceptive Behaviors in A Mouse Model of Fibrous Dysplasia

Topic: Basic Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, , , , , , Pharmacological interventions, Transgenic models, Behavioral studies, , ,

Background and Aims: Fibrous dysplasia (FD) is a rare bone disease in which bone tissue is replaced by a woven fibro-osseus tissue, the pathological mechanism of which is somatic gain-of-function GNAS mutation1. Many patients with FD experience pain and identify pain relief as a high research priority2,3. Previous work4 has suggested that pain-related pro-inflammatory cytokines and growth factors, including nerve growth factor (NGF), are unregulated in FD. Therefore, the aim of this study is to identify the effects of the anti-NGF antibody tanezumab on pain-like behaviors in a mouse model of FD.

Methods: A doxycycline inducible transgenic mouse model expressing the GNAS mutation was used5. The mice were housed in Digital Ventilated Cages (DVCs) where their activities are automatically tracked. The effect of tanezumab (10 mg/kg) or vehicle injection was evaluated after 48 hours by Blackbox and Vertical climbing. The Blackbox rodent imaging platform measures footprint pressure and tracks body posture to enable automated behavior identification. For this assessment, mice were individually placed in dark chambers and recorded for 5 minutes. Voluntary climbing behavior was assessed by placing each mouse on a vertically oriented cylindrical mesh grid and recording for 12 minutes.

Results: Significant behavioral deficits were observed in FD mice compared to control mice in DVC, Blackbox and Vertical climbing assays. Locomotion activity was significantly improved in FD mice treated with tanezumab (10mg/kg, n=9) compared with the FD-vehicle group (n=9) in DVC assay (p=0.0028) following the first injection of tanezumab. At Day 9, the FD-tanezumab group showed significant improvements over the FD-vehicle group in both footprint pressure from Blackbox assay (p=0.0379) and standing time from Vertical climbing assay (p=0.0494).

Conclusions: In conclusion, three different novel behavioral assays revealed a significant difference on pain-like behaviors between the control and the FD mice after doxycycline induction. Additionally, this study demonstrated blocking NGF could attenuate the pain-like behaviors of the FD mice suggesting NGF as a contributor to pain in FD.

References: 1. Golden E, Heijden H van der, Ren B, et al. Phenotyping Pain in Patients With Fibrous Dysplasia/McCune-Albright Syndrome. J Clin Endocrinol Metab 2024;109(3):771–782.
2. Majoor BCJ, Andela CD, Bruggemann J, et al. Determinants of impaired quality of life in patients with fibrous dysplasia. Orphanet Journal of Rare Diseases 2017;12(1):80.
3. Kelly MH, Brillante B, Collins MT. Pain in fibrous dysplasia of bone: age-related changes and the anatomical distribution of skeletal lesions. Osteoporos Int 2008;19(1):57–63.
4. Hopkins C, De Castro LF, Benthin J, et al. Pain in fibrous dysplasia: identifying nociceptive mechanisms in a preclinical model. Journal of Bone and Mineral Research 2025;zjaf039.
5. Zhao X, Deng P, Iglesias-Bartolome R, et al. Expression of an active Gαs mutant in skeletal stem cells is sufficient and necessary for fibrous dysplasia initiation and maintenance. Proceedings of the National Academy of Sciences 2018;115(3):E428–E437.

Presenting Author: Yingyu Tang
Submitting Author: Yingyu Tang

Senior Author: Anne-Marie Heegaard

IASP 2026 Global Year theme of Neuropathic Pain: No

• Andrea Søeberg: BSc - Department of Drug design and Pharmacology, Faculty of Health and Medical Science, University of Copenhagen, Denmark
• Chrysanthi Bozini: BSc - Department of Drug design and Pharmacology, Faculty of Health and Medical Science, University of Copenhagen, Denmark
• Chelsea Hopkins: PhD - School of Psychology and Neuroscience, University of Glasgow, Scotland, UK
• Morten Egebjerg Malmberg: Msc - Department of Veterinary and Animal Sciences, Faculty of Health and Medical Science, University of Copenhagen, Denmark
• Pravallika Manjappa: PhD - AstraZeneca, UK
• Sara Hestehave: PhD - Department of Veterinary and Animal Sciences, Faculty of Health and Medical Science, University of Copenhagen, Denmark
• Anne-Marie Heegaard: PhD, MD - Department of Drug design and Pharmacology, Faculty of Health and Medical Science, University of Copenhagen, Denmark