NIDA-supported researchers Drs. George Wilcox and Carolyn Fairbanks at the University of Minnesota in Minneapolis and Dr. Robert Yezierski at the University of Miami have demonstrated that a recently discovered compound appears to alleviate chronic pain. The investigators, led by Dr. Wilcox, are studying agmatine, an amino-acid-like substance produced in the brain. They have found that in laboratory mice and rats, agmatine appears to relieve chronic pain caused by nerve damage and inflammation. (See "Acute vs. Chronic Pain," below.)

"Agmatine appears to selectively reduce the chronic pain resulting from nerve damage or inflammation, but not the acute pain caused by normal injury."

The research team injected either agmatine or saline solution into the spines of rodents that had pain associated with nerve damage due to chemically induced inflammation or surgically induced spinal cord injury. The researchers found that the animals treated with agmatine showed reduced sensitivity to this pain.

In this microscopic image of a mouse spinal cord, the long, thin strands show cellular processes or fibers containing agmatine. When administered from outside the body, agmatine appears to reduce the symptoms of chronic pain.

"Agmatine seems to interrupt the cascade of changes that occur in the nervous system after nerve damage," says Dr. Wilcox. Agmatine, thought to be a neurotransmitter like dopamine or serotonin-substances that act as chemical messengers between nerve cells-counters the effect of another brain chemical, glutamate. Glutamate, which is released in large quantities following injuries, promotes pain by damaging and destroying nerve cells.

"Agmatine is not a typical pain reliever," says Dr. Fairbanks. "It appears to selectively reduce the chronic pain resulting from nerve damage or inflammation, but not the acute pain caused by normal injury."

In the study with rodents, Dr. Wilcox notes, "the relief provided by agmatine appeared to be permanent, unlike the temporary relief provided by medications like morphine." Moreover, agmatine seemed to produce none of the serious side effects seen with morphine and related drugs, such as sedation, respiratory depression, and loss of coordination.

Agmatine still has to go through many stages of testing before scientists will know if it can be a safe and effective treatment for people. Meanwhile, these early findings with the compound are hopeful for chronic pain sufferers.

Fairbanks, C.A.; Schreiber, K.L.; Brewer, K.L.; Yu, C-G.; Stone, L.S.; Kitto, K.F.; Nguyen, H.O.; Grocholski, B.M.; Shoeman, D.W.; Kehl, L.J.; Regunathan, S.; Reis. D.J.; Yezierski, R.P.; and Wilcox, G.L. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury. Proceedings of the National Academy of Sciences 97(19):10584-10589, 2000. [Abstract]