Reducing Maladaptive Sensory Neuronal Growth to Target Below-Level Pain Following Spinal Cord Injury
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Date
2015-04-28
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Conner, Blaire
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Abstract
Chronic neuropathic pain is a common, debilitating consequence of spinal cord injury (SCI). Up to 94% of the SCI population suffers from SCI pain, with over half reporting it as their worst medical problem. Modern day methods of SCI pain management are ineffective. Recent evidence suggests that this pain is due, in part, to aberrant outgrowth of sensory neurons at and below the level of injury. We have previously shown that SCI results in phosphorylation (inhibition) of glycogen synthase kinase-3β (GSK-3β), a key regulator of neuronal growth. The purpose of this study was to characterize the time-dependent nature of SCI-induced sensory neuron outgrowth below the level of injury, and to establish an optimal timeframe for application of a GSK-3β activator, in an effort to block SCI-induced sprouting and the development of below-level pain. Long-Evans rats received a dorsal horn injection of quisqualic acid (SCI) or saline (sham operated control) and were sacrificed 1, 3, 14 and 22 days following surgery. At the designated time points, DRGs ipsilateral to the site of injection were disassociated, cultured and analyzed for neurite outgrowth and length. In the second experimental approach, rats received intrathecal delivery of the GSK-3β activator (LY294002) the first 3 days after injury and were sacrificed 14 days following surgery. Time course studies show a graded increase in below-level growth responses following SCI. Intrathecal administration of LY294002, initiated at the time of injury, significantly reduced below-level DRG neurite outgrowth 14 days post-SCI. Additionally, LY294002 treatment prevented the development of below-level hyperalgesia. Based on these results GSK-3β may be involved in the modulation of abnormal sensory growth responses following SCI, and might constitute a new therapeutic target to prevent below-level SCI pain.
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Physical Therapy Department
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Conner, Blaire. (2015). Reducing Maladaptive Sensory Neuronal Growth to Target Below-Level Pain Following Spinal Cord Injury. Unpublished manuscript, Honors College, East Carolina University, Greenville N.C.