It is common that after spinal cord injury patients develop a spastic syndrome that is characterized by hyperactive tendon jerks, increased muscle tone, clonus and involuntary flexor withdrawal and extensor spasms. These symptoms are very debilitating and distressing as they can interfere with residual motor function, produce pain and disrupt sleep. The neuronal mechanisms that produce muscle spasticity in the human remain largely unknown. However, recent studies from spinal cord injured rats have shown that the development of muscle spasticity is produced by a recovery of the excitability of motoneurons below the injury through the activation of dendritic persistent inward currents (PICs). These PICs produce sustained depolarizations of the cell (plateau potentials) and amplify and prolong the response of motoneurons to transient sensory inputs and ultimately generate exaggerated and sustained reflex responses characteristic of the spastic syndrome. Surprisingly, the redevelopment of motoneuron PICs occurs even though the levels of monoamines that facilitate PICs, such as serotonin and noradrenaline, are greatly diminished below the injury site. Through the use of paired motor unit analysis techniques in the human we have been able to distinguish intrinsically mediated plateaus on the motoneuron from synaptically mediated activation of the motoneuron. The goal of this proposal is to use this technique to determine if the recovered motoneuron PIC is different to the PIC before injury, if PIC recovery is dependent on residual levels of monoamines below the injury site and if the loss of monaminergic inhibition in the dorsal horn results in increased efficacy of spasm-triggering synaptic inputs to more readily activate motoneuron plateaus. Results from these studies will determine, for the first time, the extent to which synaptic inputs and their amplification and prolongation by active membrane properties in the motoneuron contributes to muscle spasms after spinal cord injury in the human. Once known, then rehabilitative and/or pharmacological interventions that target motoneuron transduction processes can be developed. ? ? ?
