Effects of Zolmitriptan on Sensory Transmission After Spinal Cord Injury

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.

Inclusion Criteria:

• Patients must have suffered a trauma to the spinal cord at least 1 year prior. In addition, subjects must exhibit some degree of spasticity as determined by having an Ashworth Spasticity Score greater than 1 in the ankle or knee.

Exclusion Criteria:

• If patients have damage to the nervous system other than to the spinal cord
• Pregnant women
• Elderly Patients (> 65 years)
• Alcoholic Patients
• History of ischemic cardiac, cerebrovascular or peripheral vascular syndromes
• Valvular heart disease or cardiac arrhythmias
• Other significant underlying cardiovascular disease (atherosclerotic disease, congenital heart disease)
• Uncontrolled or severe hypertension
• Hemiplegic, basilar or ophthalmologic migraine
• Hypersensitivity to Zolmitriptan or any component of the formulation
• History of Autonomic Dysreflexia
• Patients taking:
• Ergot-containing drugs
• Other 5HT1 Agonists
• MAO Inhibitors
• Cimetidine and other 1A2 Inhibitors
• Propranolol
• Selective Serotonin and Norepinephrine Reuptake Inhibitors
• Acetaminophen
• Metoclopramide
• Xylometazoline
• Oral Contraceptives