Nearly one third of Americans suffer from it, and as a nation we spend about $100 billion annually trying to get relief from it, says Daniela Salvemini, associate professor of pharmacological and physiological science at St. Louis University.

Salvemini has been studying pain for some time and her research, several years ago, led to the discovery that the production of a certain molecule plays an important role in the development of pain and inflammation. It's called peroxynitrite, and it's created when the body experiences all types of pain including acute inflammatory pain, arthritic pain and pain from nerve injury. Peroxynitrite is also produced, in the brain and spine, with prolonged use of opiates such as morphine.

The increase in peroxynitrite leads to the development of morphine-induced antinociceptive tolerance, which means that higher doses of the drug are needed to achieve adequate pain relief, Salvemini says. The higher doses lead to side effects such as constipation, nausea and respiratory depression.

"So the consensus is that chronic use of morphine causes pain and that this pain masks the pain-relieving effects of morphine. It appears to be key in the development of opiate tolerance," she says. "If we can specifically target peroxynitrite and eliminate it, we'll have remarkable improvement in treating chronic pain. And we'll also ameliorate tolerance to morphine and allow it to act properly without side effects."

Salvemini and Neumann have been looking for what she calls a "super potent molecule" to destroy peroxyinitrite and says they have a few that look promising.

Recently, the National Institutes of Health awarded Salvemini a $975,000 grant to study ways to rid the body of peroxynitrite. She and Bill Neumann, a chemist at Southern Illinois University-Edwardsville, have begun synthesizing and testing synthetic molecules that target peroxynitrite in rats.

"I don't think we'll have something that will be the one single answer," she says. "Pain is very complex, and we'll probably always need a combination."

They've found that when combined with non-steroidal drugs, such as ibuprofen, or opiates, such as morphine, the drugs are able to be more effective. The reasoning goes that this in turn should lead to fewer or no side effects from the drugs, because patients will need far lower doses.

Salvemini is confident that one day, a whole new class of painkillers will exist to use alone and in conjunction with traditional remedies for pain management.