Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


osu1261082175.pdf (4.57 MB)

ETD Abstract Container

Abstract Header

Evaluating Sensory Abnormalities in Mice after Spinal Cord Injury and the Anatomical Evidence for Likely Mechanisms

Hoschouer, Emily Laurel
http://rave.ohiolink.edu/etdc/view?acc_num=osu1261082175

Abstract Details

2010, Doctor of Philosophy, Ohio State University, Neuroscience.
Spinal cord injury (SCI) results in devastating losses in motor and sensory function. In addition to the loss of function, a large proportion of individuals with SCI also suffer from neuropathic pain, dysesthesias, and paresthesias, which have more detrimental impact on quality of life. Several animal models of neuropathic pain, including those specific to SCI, have been developed, leading to a much broader understanding of chronic pain mechanisms. However, the potential of transgenic mice to contribute to the understanding of the mechanisms of development of chronic pain after SCI remains largely untapped, in part due to the lack of sensory measures applicable to and characterized in spinal cord injured mice. The overarching goal of this research was to document practical assessments of mouse sensory dysfunction, including evoked and spontaneous dysfunctions, to characterize aberrant responses, and to evaluate the likely anatomical substrates of neuropathic pain. In the first set of experiments, we hypothesized that the L1 cell adhesion molecule would contribute to sensory fiber sprouting and therefore altered sensory responses after SCI. To test this, we compared sensory responses and histology in L1 knockout (KO) and wild-type (WT) littermates after SCI. We found that KO and WT mice developed hypersensitivity to thermal stimuli after SCI, but that KO mice recovered normal responsiveness by 4 weeks post-injury. Anatomically, L1 KO mice had diminished sprouting of small-diameter nociceptive fibers, and increased protein kinase C γ (PKCγ) expression in the dorsal horn of the lumbar spinal cord. These results suggest that L1 is necessary for the maintenance of thermal hyperalgesia, and that it acts through sprouting and PKCγ-related mechanisms. For the second set of experiments, we hypothesized that patterns of sensory dysfunction in mice after SCI would depend on lesion severity, testing modality, and body area tested. We found that in the hind paws, hypersensitivity to thermal stimuli developed independent of injury severity. In contrast, hind paw mechanical sensitivity decreased after mild, moderate, or complete transection injuries; but after severe contusion with limited axonal sparing, there was enhanced sensitivity to mechanical stimuli. On the dorsal trunk, mechanical and pin prick testing demonstrated diminished sensitivity at and below the injury level, while responses above the level of the injury were largely unchanged. In the next set of experiments, we tested the hypothesis that sensory stimulation prior to SCI could induce overgrooming, an indication of neuropathic pain or dysesthesia after SCI. We found that both mechanical and nociceptive stimulation were capable of producing pathological overgrooming when combined with SCI. Finally, we analyzed anatomical evidence of likely pain substrates after SCI. We hypothesized that small diameter afferent sprouting and PKCγ upregulation would correspond with the thermal hyper-responsiveness evident at all injury severities, while microglia and astrocytes would increase corresponding with mechanical allodynia, and would only be present in the lumbar spinal cord after the most severe injuries. We found that small-diameter afferent sprouting and increased microglial presence corresponded with mechanical sensitivity, while astrocyte activation and PKCγ upregulation had no relation to thermal hyper-responsiveness or mechanical sensitivity.
Lyn B. Jakeman (Advisor)
Christine Beattie (Committee Member)
Robert Stephens, Jr (Committee Member)
John Buford (Committee Member)
D. Michele Basso (Committee Member)
200 p.
Neurology
allodynia; hyperalgesia; neuropathic pain; sensory testing; mice; spinal cord injury

Recommended Citations

Citations

  • Hoschouer, E. L. (2010). Evaluating Sensory Abnormalities in Mice after Spinal Cord Injury and the Anatomical Evidence for Likely Mechanisms [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1261082175

    APA Style (7th edition)

  • Hoschouer, Emily. Evaluating Sensory Abnormalities in Mice after Spinal Cord Injury and the Anatomical Evidence for Likely Mechanisms. 2010. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1261082175.

    MLA Style (8th edition)

  • Hoschouer, Emily. "Evaluating Sensory Abnormalities in Mice after Spinal Cord Injury and the Anatomical Evidence for Likely Mechanisms." Doctoral dissertation, Ohio State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=osu1261082175

    Chicago Manual of Style (17th edition)

osu1261082175
1,025
© 2009, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.