Aberrant sensory responses are dependent on lesion severity after spinal cord contusion injury in mice

Following spinal cord injury (SCI), individuals lose normal sensation and often develop debilitating neuropathic pain. Basic research has helped to elucidate many of the underlying mechanisms, but unanswered questions remain concerning how sensation changes after SCI and potential negative consequences of regenerative therapies. Mouse models provide an opportunity to explore these questions using genetic markers and manipulations. However, despite the increasing use of mice in pain and sensory research, the responses to sensory stimuli after SCI are poorly characterized in this species. This study evaluated behavioral responses to mechanical and nociceptive stimuli applied to the hindlimbs and the dorsal trunk in C57BL/6 mice after mid-thoracic SCI. Adult mice were subjected to laminectomy, contusion injuries of different severities, or complete transections to test the hypothesis that the patterns of sensory pathology depend on the extent of tissue damage at the injury site. In the hind paws, hyper-responsiveness to a heat stimulus developed independent of injury severity, while mechanical sensitivity decreased, except after the most severe contusion injuries sparing less than 2% of the white matter at the injury site, when enhanced sensitivity was observed. On the trunk, mechanical and pin prick testing revealed diminished sensitivity at and below the injury level, while responses above the level of the injury were unchanged. The contrast in injury severity threshold for thermal and mechanical hypersensitivity in the hind paws suggests that these responses have different underlying mechanisms. These results establish essential baseline information for murine studies of pain and changes in sensation after SCI.