Spinal Cord Injuries Clinical Trial
Official title:
Phase 2: Effects of Zolmitriptan on Sensory Afferent Transmission After Spinal Cord Injury
After spinal cord injury, patients develop a spastic syndrome that is characterized by
hyperactive reflexes, increased muscle tone, clonus and involuntary muscle spasms. The
neuronal mechanisms behind the development of spasticity remain largely unknown, though
animal experiments have shown that changes occur both at the level of the motoneuron and
sensory neurons. This project aims to examine the changes that occur in the modulation of
sensory afferent transmission after spinal cord injury, and how these changes can contribute
to the triggering and initiation of muscle spasms after chronic spinal cord injury in
humans.
It is known that after spinal cord injury, the majority of descending sources of monoamines,
such as serotonin (5HT), are abolished. Animal experiments have shown that 5HT receptors on
sensory neurons in the spinal cord are responsible for inhibiting sensory transmission. As a
result, after spinal cord injury these receptors are no longer activated below an injury,
resulting in the production of large, long excitatory responses in the motoneuron when
sensory are activated. This large sensory activation of the motoneuron can, in turn,
activate a long response in the motoneuron to produce an involuntary muscle spasm. The aim
of our study is to determine whether, similar to animal experiments, the 5HT1 receptors are
responsible for sensory inhibition in spinal cord injured subjects, and whether activating
these receptors (through the 5HT1 agonist Zolmitriptan) will restore the normal inhibition
of sensory transmission that is lost after injury, thereby resulting in a decrease in the
initiation of involuntary muscle spasms.
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