A new NIH-funded study shows that a specific gene variant in humans affects both sensitivity to short-term (acute) pain in healthy volunteers and the risk of developing chronic pain after one kind of back surgery. Blocking increased activity of this gene after nerve injury or inflammation in animals prevented development of chronic pain.
The gene in this study, GCH1, codes for an enzyme called GTP cyclohydrolase. The study suggests that inhibiting GTP cyclohydrolase activity might help to prevent or treat chronic pain, which affects as many as 50 million people in the United States. Doctors also may be able to screen people for the gene variant to predict their risk of chronic post-surgical pain before they undergo surgery. The results appear in the October 22, 2006, advance online publication of Nature Medicine.*
"This is a completely new pathway that contributes to the development of pain," says Clifford J. Woolf, M.D., of Massachusetts General Hospital and Harvard Medical School in Boston, who led the research. "The study shows that we inherit the extent to which we feel pain, both under normal conditions and after damage to the nervous system."
Dr. Woolf carried out the study in collaboration with Mitchell B. Max, M.D., of the National Institute of Dental and Craniofacial Research (NIDCR) in Bethesda, Maryland, and colleagues at the National Institute on Alcoholism Abuse and Alcoholism (NIAAA) and elsewhere. Dr. Woolf's work was funded by the National Institute of Neurological Disorders and Stroke (NINDS). The research team also received funding from NIDCR, NIAAA, and other organizations.
The researchers originally identified GCH1 by preclinical screening for genes that undergo significant changes in expression after sciatic nerve injury. GCH1 is one of several genes that code for enzymes needed to produce a chemical called tetrahydrobiopterin (BH4). Previous studies have shown that BH4 is an essential ingredient in the process that produces dopamine and several other nerve-signaling chemicals (neurotransmitters). It also plays other important roles in the body. However, this study is the first to show that GCH1 and BH4 play a role in pain.