Osteogenesis imperfecta (OI) is a congenital disorder caused most often by dominant mutations in the COL1A1 or COL1A2 genes that encode the alpha chains of type I collagen. Severe forms of OI are associated with skeletal deformities and frequent fractures. Skeletal pain can occur acutely after fracture, but also arises chronically without preceding fractures. In this study we assessed OI-associated pain in the Col1a1Jrt/+ mouse, a recently developed model of severe dominant OI. Similar to severe OI in humans, this mouse has significant skeletal abnormalities and develops spontaneous fractures, joint dislocations and vertebral deformities. In this model, we investigated behavioral measures of pain and functional impairment. Significant hypersensitivity to mechanical, heat and cold stimuli, assessed by von Frey filaments, radiant heat paw withdrawal and the acetone tests, respectively, were observed in OI compared to control wildtype littermates. OI mice also displayed reduced motor activity in the running wheel and open field assays. Immunocytochemical analysis revealed no changes between OI and WT mice in innervation of the glabrous skin of the hindpaw or in expression of the pain-related neuropeptide calcitonin gene-related protein in sensory neurons. In contrast, increased sensitivity to mechanical and cold stimulation strongly correlated with the extent of skeletal deformities in OI mice. Thus, we demonstrated that the Col1a1Jrt/+ mouse model of severe OI has hypersensitivity to mechanical and thermal stimuli, consistent with a state of chronic pain.
|Original language||English (US)|
|Number of pages||7|
|State||Published - Dec 1 2015|
Bibliographical noteFunding Information:
This study was supported by operating grants from the Canadian Institutes for Health Research (SVK ( MOP-77643 ), AR ( MOP-136903 , MOP-79411 ), LSS ( MOP-126046 )), The Shriners of North America (FR) and infrastructure and travel support from the Quebec Pain Research Network and the Quebec Network for Oral and Bone Health Research . DMA was supported by the Ministry of Higher Education, Egypt . CM is supported by a PhD studentship from the Louise and Alan Edwards Foundation . FR received support from the Chercheur-Boursier Clinicien program of the Fonds de Recherche du Québec . SVK holds the Canada Research Chair in Osteoclast Biology. The sponsor(s) had no role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the article for publication.
© 2015 Elsevier Inc.
- Collagen mutation
- Osteogenesis imperfecta
- Skeletal deformity