Spinal cord injury leads to severe problems involving impaired motor, sensory and autonomic functions. After spinal injury there is an initial phase of hypo-reflexia followed by hyper-reflexia, often referred to as spasticity. Previous studies have suggested a relationship between the reappearance of endogenous plateau potentials in motor neurons and the development of spasticity after spinalization. To unravel the molecular mechanisms underlying the increased excitability of motor neurons and the return of plateau potentials below a spinal cord injury we investigated changes in gene expression in this cell population. We adopted a rat tail-spasticity model with a caudal spinal transection that causes a progressive development of spasticity from its onset after two to three weeks until two months post injury. Gene expression changes of fluorescently identified tail motor neurons were studied 21 and 60 days post injury. The motor neurons undergo substantial transcriptional regulation in response to injury. The patterns of differential expression show similarities at both time points, though there are 20 % more differentially expressed genes 60 days compared to 21 days post injury. The study identifies targets of regulation relating to both ion channels and receptors implicated in the endogenous expression of plateaux. The regulation of excitatory and inhibitory signal transduction indicates a shift in the balance towards increased excitability, where the glutamatergic NMDA receptor complex together with cholinergic system is up-regulated and the GABAA receptor system is down-regulated. The genes of the pore-forming proteins Cav1.3 and Nav1.6 were not up-regulated, while genes of proteins such as non-pore forming subunits and intracellular pathways known to modulate receptor and channel trafficking, kinetics and conductivity showed marked regulation. On the basis of the identified changes in global gene expression in motor neurons, the present investigation opens up for new potential targets for treatment of motor dysfunction following spinal cord injury.