Muscle Spasticity, Spinal Cord Injuries
Conditions
Brief summary
The main goal of this research is to understand the neuronal mechanisms that mediate the development of spasticity and motor dysfunction after spinal cord injury. The investigators examine how neurons and neuronal circuits in an injured nervous system adapt to produce the uncontrolled and unwanted muscle contractions that affect the majority (80%) of patients with spinal cord injury. One of the neurons that the investigators study is the motoneuron that excites the muscles of the limbs to produce movement. Previously, the investigators have shown that after spinal cord injury, the excessive and uncontrolled activity of motoneurons during muscle spasms is mediated, in large part, by the activation of calcium currents in the human motoneuron. In human patients the investigators have used recordings from single muscle fibres to estimate the contribution of these calcium currents in activating the motoneuron during muscle spasms. In this proposal, the investigators study why motoneurons recover these calcium currents and self-sustained activity after chronic spinal cord injury. Because the calcium currents require the presence of the monoamine serotonin (5HT) to activate, and this monoamine is greatly reduced after injury, the investigators examine if the calcium currents recover because the 5HT receptors become spontaneously active without the need for 5HT to bind to the receptor, which the investigators hypothesize to be one of the causes of spasticity after spinal cord injury. This research will pave the way to develop new pharmacological and rehabilitative therapies to both control spasticity after spinal cord injury and augment residual motor movements.
Interventions
None listed
Sponsors
University of Alberta
Eligibility
Sex/Gender
ALL
Age
17 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Patients must have suffered a trauma to the spinal cord at least 6 months ago or longer. In addition, subjects must exhibit some degree of spasticity as determined by having an Ashworth Spasticity Score, as assessed by a physical therapist, greater than 1.
Exclusion criteria
* If patients have damage to the nervous system other than to the spinal cord * Pregnant women * Elderly Patients and debilitated patients * Alcoholic Patients * Patients with: * Known or suspected allergy to the medication or its ingredients * Cardiovascular disease * Hypotension * Coronary artery disease * Reduced liver or kidney function * Comatose or depressed states due to CNS depressants * Blood dyscrasias * Bone marrow depression * History of seizures * Respiratory problems * Hypocalcemia * Monoamine oxidase inhibitor therapy * Angle-closure glaucoma * Stenosing peptic ulcer * Symptomatic prostatic hypertrophy * Bladder neck obstruction * Pyloroduodenal obstruction * History of bronchial asthma * Increased intraocular pressure * Hyperthyroidism * Cardiovascular disease * Hypertension * Patients taking: * Amphetamines * Antihistamines-second generation * Anticonvulsants * Anticholinergics * CNS depressants * Antidepressants * Hypotensive agents * Levodopa * Lithium
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cutaneomuscular Reflex Responses | Change after drug intake at baseline, 30minutes, 60minutes, 90minutes and 120minutes | Tibialis anterior reflex responses evoked by stimulation of the medial arch of the foot will be measured before and after drug administration. |
| Paired motor unit recordings | Change at baseline and 30, 60, 90 and 120min after drug intake | We obtain paired motor unit recordings to determine changes in neuronal excitability after drug intake in incomplete spinal-cord injured subjects only. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Blood pressure and Heart rate | Change at baseline and 30, 60, 90, 120 minutes after drug intake | We measure blood pressure and heart rate to determine the safety of the drug during the experiment and whether we can continue safely. |
Countries
Canada
Outcome results
None listed