Allowing the viewing of animated cartoons by pediatric surgical patients is a very effective method to alleviate preoperative anxiety. Our study suggests that this intervention is an inexpensive, easy to administer, and comprehensive method for anxiety reduction in the pediatric surgical population.

Perioperative intravenous administration of magnesium sulfate did not increase CSF magnesium concentration and had no effects on postoperative pain. However, an inverse relation between cumulative postoperative analgesic consumption and the CSF magnesium concentration was observed. These results suggest that perioperative intravenous magnesium infusion may not be useful for preventing postoperative pain.

T-type Ca2ϩ channels are believed to play an important role in pain perception, and anesthetic steroids such as alphaxalone and allopregnanolone, which have a 5␣-configuration at the steroid A, B ring fusion, are known to inhibit T-type Ca 2ϩ channels and cause analgesia in a thermal nociceptive model (Soc Neurosci Abstr 29:657.9, 2003). To define further the structure-activity relationships for steroid analgesia, we synthesized and examined a series of 5␤-reduced steroids for their ability to induce thermal antinociception in rats when injected locally into the peripheral receptive fields of the nociceptors and studied their effects on T-type Ca 2ϩ channel function in vitro. We found that most of the steroids completely blocked T-type Ca 2ϩ currents in vitro with IC 50 values at a holding potential of Ϫ90 mV ranging from 2.8 to 40 M. T current blockade exhibited mild voltage-dependence, suggesting that 5␤-reduced neuroactive steroids stabilize inactive states of the channel. For the most potent steroids, we found that other voltage-gated currents were not significantly affected at concentrations that produce nearly maximal blockade of T currents. All tested compounds induced dose-dependent analgesia in thermal nociceptive testing; the most potent effect (ED 50 , 30 ng/100 l) obtained with a compound [(3␤,5␤,17␤)-3-hydroxyandrostane-17-carbonitrile] that was also the most effective blocker of T currents. Compared with previously studied 5␣-reduced steroids, these 5␤-reduced steroids are more efficacious blockers of neuronal T-type Ca 2ϩ channels and are potentially useful as new experimental reagents for understanding the role of neuronal T-type Ca 2ϩ channels in peripheral pain pathways.

Cardiac sodium channels (Na(v)1.5) comprise a pore-forming alpha-subunit and auxiliary beta-subunits that modulate channel function. In the heart, beta1 is expressed throughout the atria and ventricles, whilst beta3 is present only in the ventricles and Purkinje fibers. In view of this expression pattern, we determined the effects of beta3 and beta1 co-expression alone, and in combination, on Na(v)1.5 stably expressed in Chinese hamster ovary cells. The current/voltage relationship was shifted -5 mV with either beta1 or beta3 co-expression alone and -10 mV with co-expression of both beta1 and beta3. In addition, beta3 and beta1/beta3 co-expression accelerated macroscopic current decay. There were significant hyperpolarizing shifts in equilibrium gating relationships with co-expression of beta1 and beta3 alone and in combination. Co-expression of beta1/beta3 together resulted in a greater hyperpolarizing shift in channel availability, and an increase in the slopes of equilibrium gating relationships. Co-expression of beta3 and beta1/beta3, but not beta1, slowed recovery from inactivation at -90 mV. Development of inactivation at -70 and -50 mV was accelerated by beta-subunit co-expression alone and in combination. beta-Subunit co-expression also reduced the late Na current measured at 200 ms. In conclusion, beta-subunits modulate Na(v)1.5 gating with important differences between co-expression of beta1 and beta3 alone and beta1/beta3 together.

Electrical excitability in neurons depends on the expression and activity of voltage-gated sodium channels in the neuronal plasma membrane. The ion-conducting alpha-subunit of the channel is associated with auxiliary beta-subunits of which there are four known types. In the present study, we describe the first detailed structure/function analysis of the beta3-subunit. We correlate the effect of point mutations and deletions in beta3 with the functional properties of the sodium channel and its membrane-targeting behaviour. We show that the extracellular domain influences sodium channel gating properties, but is not required for the delivery of beta3 to the plasma membrane when expressed with the alpha-subunit. In contrast, the intracellular domain is essential for correct subunit targeting. Our results reveal the crucial importance of the Cys21-Cys96 disulphide bond in maintaining the functionally correct beta3 structure and establish a role for a second putative disulphide bond (Cys2-Cys24) in modulating channel inactivation kinetics. Surprisingly, our results imply that the wild-type beta3 molecule can traverse the secretory pathway independently of the alpha-subunit.