title: APP/SOD1 overexpressing mice present reduced neuropathic pain sensitivity.
abstract: There are controversies regarding pain expression in mentally disabled people, including Down syndrome patients. The aim of this study was to examine neuropathic pain-related behavior and peripheral nerve regeneration in mouse model of Down syndrome. Sciatic nerves of double transgenic mice, overexpressing both amyloid precursor protein (APP) and Cu/Zn superoxide dismutase (SOD1) genes, and FVB/N wild type mice were transected and immediately resutured. Evaluation of autotomy and functional recovery was carried out during 4-week follow-up. We found markedly less severe autotomy in transgenic animals, although the onset of autotomy was significantly delayed in control mice. Interestingly, neuroma formation at the injury site was significantly more prominent in transgenic animals. Sciatic function index outcome was better in transgenic mice than in wild-type group. Histological evaluation revealed no statistically significant differences in the number of GAP-43-positive growth cones and macrophages in the distal stump of the transected nerve between groups. However, in transgenic animals, the regenerating axons were arranged more chaotically. The number of Schwann cells in the distal stump of the transected nerves was significantly lower in transgenic mice. The number of surviving motoneurons was markedly decreased in transgenic group. We measured also the atrophy of denervated muscles and found it decreased in APP/SOD1 overexpressing mice. Taken together, in this model of Down syndrome, we observed increased neuroma formation and decreased autotomy after peripheral nerve injury. Our findings suggest that APP/SOD1 overexpressing mice are less sensitive for neuropathic pain associated with neuroma.
authors: Department of Child Neurology, The Children's Memorial Health Institute, Warsaw, Poland. k.kotulska@czd.pl
authors: Katarzyna
authors: K
authors: Kotulska
authors: Magdalena
authors: M
authors: Larysz-Brysz
authors: Marie
authors: M
authors: LePecheur
authors: Wiesław
authors: W
authors: Marcol
authors: Edyta
authors: E
authors: Olakowska
authors: Joanna
authors: J
authors: Lewin-Kowalik
authors: Jacqueline
authors: J
authors: London