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  • http://hdl.handle.net/10402/era.24981
  • Electrophysiological Signature of Neuropathic Pain
  • Chen, Yishen
  • English
  • pain
    CCI
    axotomy
    electrophysiology
    AMPAR
  • Jan 6, 2012 3:46 PM
  • Thesis
  • English
  • Adobe PDF
  • 4013717 bytes
  • Neuropathic pain afflicts 1.5-3% of the general population. It can be initiated by traumatic nerve injuries or diseases such as diabetic or post-herpetic neuropathy. Neuropathic pain is often initiated by abnormal spontaneous activity in sensory neurons and this provokes increased excitability of neurons in the dorsal horn of the spinal cord in a process known as “central sensitization”. However, different types of peripheral nerve injury may send different signals to the spinal cord. Therefore, electrophysiological and pharmacological methods were used to examine the properties of interneurons in substantia gelatinosa of rat spinal dorsal horn in two common neuropathic pain models: sciatic nerve axotomy and chronic constriction injury (CCI). Axotomy increased synaptic excitation of putative excitatory neurons and decreased synaptic excitation of putative inhibitory neurons. Axotomy produced similar but weaker changes than CCI in electrophysiological properties of substantia gelatinosa neurons. Axotomy reduced the functional expression of voltage gated Ca2+ channels and reduced expression presynaptic Ca2+ permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors on primary afferent terminals but CCI did not. Whereas CCI decreased the proportion of Ca2+ permeable AMPA receptors on the cell bodies of tonic firing putative inhibitory neurons, axotomy did not. Whereas CCI increased the proportion of Ca2+ permeable AMPA receptors in delay firing putative excitatory neurons, axotomy did not. The changes in excitatory synaptic transmission produced by both axotomy and CCI likely contribute to the central sensitization that underlies the generation of neuropathic pain. The tendency for CCI to generate more profound changes in the dorsal horn than axotomy may relate to the stronger inflammatory response it produces and the probability that axotomy interrupts peripheral trophic support of presynaptic Ca2+ permeable AMPA receptors.
  • Chen, Yishen (2009). J. Physiology http://jn.physiology.org/cgi/content/abstract/102/6/3203
  • Doctoral
  • Doctor of Philosophy
  • Department of Pharmacology
  • Spring 2012
  • Smith, Peter A (Department of Pharmacology and Center for Neuroscience)
  • Greer, John (Department of Physiology)
    Tse, Fred (Department of Pharmacology)
    Funk, Greg (Department of Physiology)
    Kerr, Brad (Department of Anesthesiology and Pain Medicine)
    Callister, Robert (Department of Anatomy, University of Newcastle)