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  • http://hdl.handle.net/10048/1190
  • The role of serotonin receptors in spasticity after spinal cord injury
  • Murray, Katherine
  • en_US
  • Spinal cord injury
    Spasticity
    Serotonin
    Constitutive activity
    sensory afferent transmission
  • Jun 25, 2010 6:49 PM
  • Thesis
  • en_US
  • Adobe PDF
  • 2695788 bytes
  • Brainstem derived serotonin (5-HT) normally facilitates spinal motoneuron excitability and inhibits sensory afferent transmission and associated spinal reflexes. Because the 5-HT innervation of the spinal cord is almost exclusively derived from brainstem neurons, spinal cord injury leads to an immediate and dramatic loss of 5-HT and this in turn leads to the simultaneous loss of motoneuron excitability and increase (disinhibition) of sensory afferent transmission. This thesis examined how spinal cord 5-HT receptors adapt over the months after SCI (chronic injury) to compensate for the loss of 5-HT. We showed that after SCI 5-HT2B and 5-HT2C receptors become constitutively active (active in the absence of 5-HT) with chronic injury, and this leads to a recovery of motoneuron excitability and contributes to the recovery of locomotor function. Unfortunately, this also contributes to the development of muscle spasms when combined with the disinhibition of sensory afferent transmission. In contrast, 5-HT1 receptors that modulate sensory afferent transmission do not become constitutively active after chronic SCI, and this contributes to the continued disinhibition of sensory afferent transmission and associated hyperreflexia and muscle spasms after chronic SCI. However, exogenous application of 5-HT1B and 5-HT1F receptor agonists can restore inhibition over sensory afferent transmission and ultimately reduce muscle spasms. In summary, 5-HT2 receptors exhibit a remarkable adaptation to the loss of 5-HT with SCI, whereas 5-HT1 receptors do not. Understanding and promoting this natural plasticity may help in the development of better therapeutic interventions for treating SCI.
  • Doctoral
  • Doctor of Philosophy
  • Centre for Neuroscience
  • Fall 2010
  • Bennett, David (Rehabilitation Medicine)

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