Effects of Zolmitriptan on Sensory 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.
Spinal Cord Injuries
|Official Title:||Phase 2: Effects of Zolmitriptan on Sensory Afferent Transmission After Spinal Cord Injury|
- Change in H-reflex amplitude from baseline [ Time Frame: Pre baseline, 30, 60, 90 and 120 minutes ] [ Designated as safety issue: No ]H-reflexes in the soleus muscle will be evoked by stimulation of the posterior tibial nerve. The response will recorded before drug intake, and every 30 minutes after drug intake up to 2 hours to determine the change in the response as a result of drug intake.
- Change in Cutaneomuscular Reflex Responses from baseline [ Time Frame: Pre baseline, 30, 60, 90, 120 minutes ] [ Designated as safety issue: No ]Tibialis anterior reflex responses will be recorded after medial arch stimulation of the foot. Recordings will be taken to provide a pre-drug baseline and then every 30 minutes after drug intake up to 2 hrs to determine the change in these reflex responses after drug intake.
- Change in Blood pressure [ Time Frame: Pre and 60min, 120min post drug ] [ Designated as safety issue: No ]Blood pressure will be measured to determine the safety of the drug during the study.
- Change in Heart rate [ Time Frame: Predrug, 60min and 120min after drug ] [ Designated as safety issue: No ]Heart rate will be monitored before drug intake and 60 and 120 min after drug intake so as to monitor vital signs.
|Study Start Date:||January 2012|
|Study Completion Date:||November 2012|
|Primary Completion Date:||May 2012 (Final data collection date for primary outcome measure)|
Uninjured control subjects
Uninjured, control subjects who are not taking any of the contraindicated drugs.
Spinal-cord injured subjects
Patients who have suffered a spinal cord injury (>1year ago).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01587170
|University of Alberta|
|Edmonton, Alberta, Canada|
|Principal Investigator:||Monica A Gorassini, PhD||University of Alberta|
|Principal Investigator:||Ming Chan, MD, PhD||University of Alberta|