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. 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 study shows that we inherit the extent to which we feel pain, both under normal conditions and after damage to the nervous system," says Clifford J. Woolf, M.D., of Massachusetts General Hospital and Harvard Medical School in Boston, who led the research.
The investigators tested the effects of GTP cyclohydrolase and a chemical called tetrahydrobiopterin (BH4), which is an essential ingredient in the process that produces dopamine and several other nerve-signaling chemicals (neurotransmitters), in several animal models of pain. They found that rats with neuropathic pain had greatly increased levels of GCH1 gene activity and BH4, and that injecting a GTP cyclohydrolase inhibitor called 2,4-diamino-6-hydroxypyrimidine (DAHP) alleviated hypersensitivity to pain in animal models of both neuropathic pain and inflammatory pain. In contrast, injecting BH4 greatly increased pain sensitivity.
Next, the researchers looked for GCH1 gene variations in people. They found that a specific variant of the gene, identified by combinations of one-base-pair changes in the DNA called single nucleotide polymorphisms or SNPs, protected against development of chronic post-surgical pain in people who had participated in a study of surgical diskectomy for back pain. About 28 percent of the people in the surgical study had at least one copy of the pain-protective variant of the gene. The researchers found that people with two copies of the protective version of GCH1 had the lowest risk of developing chronic pain, while those with just one copy had an intermediate risk and those with no copies of the variant had the highest risk.
MEDICA.de; Source: National Institute of Neurological Disorders and Stroke