Expression of c‑Fos in the spinal cord following nociceptive stimulation is considered to be a neurotoxic biomarker. In the present study, the immunoreactivity of c‑Fos in the spinal cord was compared between young adult (2‑3 years in dogs and 6 months in mice) and aged (10‑12 years in dogs and 24 months in mice) Beagle dogs and C57BL/6J mice. In addition, changes to neuronal distribution and damage to the spinal cord were also investigated. There were no significant differences in neuronal loss or degeneration of the spinal neurons observed in either the aged dogs or mice. Weak c‑Fos immunoreactivity was observed in the spinal neurons of the young adult animals; however, c‑Fos immunoreactivity was markedly increased in the nuclei of spinal neurons in the aged dogs and mice, as compared with that of the young adults. In conclusion, c‑Fos immunoreactivity was significantly increased without any accompanying neuronal loss in the aged spinal cord of mice and dogs, as compared with the spinal cords of the young adult animals.