The role of serotonin receptors in spasticity after spinal cord injury
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 immed...
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ndltd-LACETR-oai-collectionscanada.gc.ca-AEU.10048-11902012-03-21T22:50:08ZBennett, David (Rehabilitation Medicine)Murray, Katherine2010-06-25T18:49:05Z2010-06-25T18:49:05Z2010-06-25T18:49:05Zhttp://hdl.handle.net/10048/1190Brainstem 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.2695788 bytesapplication/pdfen_USMurray KC et al 2010. Nature Medicine. June 2010; 16(6): 694-700Spinal cord injurySpasticitySerotoninConstitutive activitysensory afferent transmissionThe role of serotonin receptors in spasticity after spinal cord injuryThesisDoctor of PhilosophyDoctoralCentre for NeuroscienceUniversity of Alberta2010-11 |
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Spinal cord injury Spasticity Serotonin Constitutive activity sensory afferent transmission |
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Spinal cord injury Spasticity Serotonin Constitutive activity sensory afferent transmission Murray, Katherine The role of serotonin receptors in spasticity after spinal cord injury |
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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. |
author2 |
Bennett, David (Rehabilitation Medicine) |
author_facet |
Bennett, David (Rehabilitation Medicine) Murray, Katherine |
author |
Murray, Katherine |
author_sort |
Murray, Katherine |
title |
The role of serotonin receptors in spasticity after spinal cord injury |
title_short |
The role of serotonin receptors in spasticity after spinal cord injury |
title_full |
The role of serotonin receptors in spasticity after spinal cord injury |
title_fullStr |
The role of serotonin receptors in spasticity after spinal cord injury |
title_full_unstemmed |
The role of serotonin receptors in spasticity after spinal cord injury |
title_sort |
role of serotonin receptors in spasticity after spinal cord injury |
publishDate |
2010 |
url |
http://hdl.handle.net/10048/1190 |
work_keys_str_mv |
AT murraykatherine theroleofserotoninreceptorsinspasticityafterspinalcordinjury AT murraykatherine roleofserotoninreceptorsinspasticityafterspinalcordinjury |
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1716390608983031808 |