A transporter that silences one of the body’s natural pain killers may yield nonaddictive pain medicines and a better understanding of AIDS patients’ increased pain perception, researchers say.

Opioid peptides are natural pain relievers with receptors throughout the body, said Dr. Vadivel Ganapathy, chair of the MCG Department of Biochemistry and Molecular Biology. Studies have shown that opioid peptide levels increase, for instance, during childbirth.

Many potent pain killers, such as morphine and codeine, override this natural pain control system by directly activating opioid peptide receptors. While pain control is effective, it comes at a price: potential addiction, immune suppression and constipation.

Researchers want to know whether safer pain killers can be developed that augment the body’s natural painkilling ability by targeting the opioid peptide transport system that terminates paincontrol communication. “This has the potential for nonaddictive pain killers that are effective, but by a different mechanism,” said Dr. Ganapathy.

Many popular antidepressants work in a similar fashion to keep the body’s natural chemical messengers, called neurotransmitters, working longer by keeping them from being taken back up into the neuron by transport systems. Chemical messengers are supposed to have limited action, but depressed patients have insufficient levels of chemicals for adequate communication between neurons. Antidepressants provide more mileage from existing neurotransmitters.

The National Institute on Drug Abuse asked him to apply for the Cutting Edge Basic Research Grant—enabling quick review for funding of novel ideas— to pursue this hypothesis as well as the molecular analysis of the transporter.

The idea that a transport system is involved is itself a novel concept. Conventional wisdom has held that an enzyme hydrolyzes, or decomposes, opioid peptide. This is the case for at least one neurotransmitter— acetylcholine, implicated in Alzheimer’s disease—which is inactivated by an enzyme, rather than being transported back into the neuron like other neurotransmitters.

But when Dr. Ganapathy watched the activity of opioid peptides, he saw it actively taken back up into the neuronal cells.

Cloning the transporter and dissecting its molecular profile will ultimately provide a model for studying whether drugs block this reuptake. In fact, the National Institute on Drug Abuse will provide Dr. Ganapathy with a number of synthetic opioid peptides to see whether they are substrates, or blockers, of this transport system.

“We know this recognizes peptides. Therefore, any chemical compound that will block the transport function