Researchers have solved at least part of the puzzle as to how anesthesia blocks pain during surgery.
They’ve discovered that anesthetic drugs bind to and interfere with certain proteins that nerve cells need to transmit signals involved in the perception of pain.
The discovery should help scientists better understand the workings of anesthetics used in surgical procedures for more than 150 years.
“It could help to design new and more specific anesthetics or allow us to lower the anesthetic concentration needed for anesthesia,” says Roger Johns, professor of anesthesiology and critical care medicine at Johns Hopkins University. “Anesthetics at higher concentrations can have dangerous side effects.”
For more than a decade, Johns and colleagues have been studying postsynaptic density protein-95, or PSD95—a scaffolding protein that helps assemble the proteins needed for neurons—nerve cells—to communicate with each other.
Previous research revealed that blocking PSD95 prevents development of certain kinds of chronic pain and reduces the amount of anesthesia required to induce its numbing effects.
In the new study, investigators show that inhalational anesthetics bind to certain sites on PSD95 and prevent excitatory neurons from transmitting signals. These protein sites appear to be important for the effectiveness of general anesthesia.
Newborns and infants
The findings may also provide clues to the cause of neurotoxicity and long-term cognitive issues reported in some newborns and infants. There has been concern in recent years that anesthesia in infants and newborns may lead to cognitive problems and impaired learning, Johns says.
“The data in rodents, primates, and humans all point in this direction, and the Food and Drug Administration has just elevated its level of concern about this issue,” says Johns, senior author of the study that is published in the journal Anesthesiology.
“We hypothesized,” he says, “that because PSD95 is also involved in neuronal synapse formation—or making the proper connections between neurons as the brain is forming—during fetal and infant brain development, the ability of anesthetics to block the action of PSD scaffolding proteins, as shown in our new study, could also be preventing correct neuronal synapse development, leading to the long-term learning and memory deficits observed.”
The research was supported by the National Institutes of Health.
Source: Johns Hopkins University