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

Abstract

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.

Delayed Applications of L1 and Chondroitinase ABC Promote Recovery after Spinal Cord Injury

“…At the same time, pain behaviors like over-grooming and licking or biting of the hind paws characteristic of spinal cord-injured BALB/C, but not C57BL/6 mice, the strain used here (Kerr and David, 2007), were not observed in either control or L1-and/or Chase-treated animals. These observations suggest that our treatments did not lead to exaggerated abnormal changes in sensation like allodynia or hyperalgesia (Hoschouer et al, 2010).…”

Decreased Spinothalamic and Dorsal Column Medial Lemniscus-Mediated Function Is Associated with Neuropathic Pain after Spinal Cord Injury

“…Similarly, Siddall and colleagues 22 found that more damage to the central and dorsal regions of the spinal cord was significantly related to increased allodynia in rats. A study by Hoschouer et al 23 showed that thermal sensitivity was increased in the hind paws irrespective of injury severity, and that severe spinal contusion in mice, with <2% white matter sparing within the STT area of the spinal cord, was associated with shorter latencies of response to light mechanical stimulation (i.e., mechanical allodynia). Other studies have proposed a complex relationship between these two pathways and suggest that nociceptive activity is dependent upon the convergence of afferent input from both the STT and DCML pathways.…”

Sensory Stimulation Prior to Spinal Cord Injury Induces Post-Injury Dysesthesia in Mice

“…Interestingly, autotomy occurs in the neuroma (complete peripheral nerve transection) model, where transmission of pain that would be caused by the self-directed behavior is eliminated (Minert et al, 2007). Similarly, OG in the present study occurs in areas denervated by the SCI (Hoschouer et al, 2009). If the mechanism of induction of self-directed behavior is similar between peripheral nerve models and our SCI model, we would expect the high incidence of OG to be due to a combination of repeated afferent stimulation, followed by an afferent barrage or cytokine release within the injured spinal cord as a result of the contusion injury.…”

“…Sensory testing on the trunk is rapid, efficient, and relevant (Hoschouer et al, 2009). However, we show here that extensive sensory testing prior to mid-thoracic contusion injury increases overgrooming, indicative of aberrant sensation.…”