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.