Muscle paralysis after spinal cord injury is partly caused by a loss of brainstem-derived serotonin (5-HT), which normally maintains motoneuron excitability by regulating crucial persistent calcium currents. Here we examine how over time motoneurons compensate for lost 5-HT to regain excitability. We find that, months after a spinal transection in rats, changes in post-transcriptional editing of 5-HT2C receptor mRNA lead to increased expression of 5-HT2C receptor isoforms that are spontaneously active (constitutively active) without 5-HT. Such constitutive receptor activity restores large persistent calcium currents in motoneurons in the absence of 5-HT. We show that this helps motoneurons recover their ability to produce sustained muscle contractions and ultimately enables recovery of motor functions such as locomotion. However, without regulation from the brain, these sustained contractions can also cause debilitating muscle spasms. Accordingly, blocking constitutively active 5-HT2C receptors with SB206553 or cyproheptadine, in both rats and humans, largely eliminates these calcium currents and muscle spasms, providing a new rationale for antispastic drug therapy.

In animals with mild lung injury, spontaneous breathing was beneficial to lung recruitment; however, in animals with severe lung injury, spontaneous breathing could worsen lung injury, and muscle paralysis might be more protective for injured lungs by preventing injuriously high transpulmonary pressure and high driving pressure.

The incidence of hypotension developed in the 1.0-l HES group was significantly lower than that in the LR and 0.5-l HES groups, showing that greater volume expansion results in less hypotension. This result indicates that the augmentation of blood volume with preloading, regardless of the fluid used, must be large enough to result in a significant increase in cardiac output for effective prevention of hypotension.

Our findings suggest that vision can influence pathologic pain, and preliminarily suggest that prism adaptation has a direction-specific and reproducible effect on not only pathologic pain but also other CRPS pathologic features. Thus, prism adaptation may be a viable cognitive treatment for CRPS.

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