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Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats

Authors

  • Young Seob Gwak,

    Corresponding author
    1. Department of Physiology, Brain Research Institute, and BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
    2. Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas
    • Department of Neurosciences and Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1043
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  • Jonghoon Kang,

    1. Virginia Bioinformatics Institute, Virginia Tech, Blacksburg, Virginia
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  • Joong Woo Leem,

    1. Department of Physiology, Brain Research Institute, and BK21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
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  • Claire E. Hulsebosch

    1. Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, Galveston, Texas
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Abstract

In this study, we examined whether a competitive AMPA receptor antagonist, NBQX, attenuates mechanical allodynia and hyperexcitability of spinal neurons in remote, caudal regions in persistent central neuropathic pain following spinal cord injury in rats. Spinal cord injury was produced by unilateral T13 transverse spinal hemisection, from dorsal to ventral, in male Sprague Dawley rats (200–250 g). Mechanical thresholds were measured behaviorally, and the excitability of wide-dynamic-range (WDR) dorsal horn neurons in the lumbar cord (L4–L5) was measured to assess central neuropathicpain. On postoperation day (POD) 28 after spinalhemisection, mechanical thresholds were significantly decreased in both injured (ipsilateral) and noninjured (contralateral) hindpaws compared with preinjury and sham control, respectively (P < 0.05). Intrathecal administration of NBQX (0.25, 0.5, 1 mM) significantly reversed the decreased mechanical thresholds in both hindpaws, dose dependently (P < 0.05). The excitability of WDR neurons was significantly enhanced on both sides of the lumbar dorsal horn 28 days following spinal hemisection (P < 0.05). The hyperexcitability of WDR neurons was attenuated by topical administration of NBQX (0.125, 0.25, 0.5, 1 mM), dose dependently (P < 0.05). Regression analysis indicated that at least three molecules of NBQX bond per receptor complex, and are needed to achieve inhibition of WDR hyperexcitability. In conclusion, our study demonstrates that the AMPA receptor plays an important role in behaviors related to the maintenance of central neuropathic pain below the level of spinal cord injury. © 2007 Wiley-Liss, Inc.

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