November 16, 2006
The transmission of unpleasant sensory signals, or nociception, once was conceived of as strictly a linear process. The signal originated at the site of the injury, was relayed to the spinal cord, then shuttled to the brain, where it was perceived as unpleasant. But recent advances in human biology show that nociception is a far more dynamic process that often involves multiple routes, or pathways, to the spinal cord and brain. Each pathway integrates a convergence of molecular signals, then relays them to the brain. A major challenge for pain researchers has been defining the myriad nociceptive routes, and, in the October 22 issue of the journal Nature Medicine, NIDCR scientists, grantees, and colleagues report a completely new pathway involved in the pain process. The pathway’s relevance to pain processing was suggested by the finding in rats that its activity increased dramatically with three different kinds of painful nerve injury. This finding was reinforced by the group’s discovery that people born with a certain variant of GCH1 gene, which participates in this pathway, are less sensitive to acute pain and less likely to develop chronic pain following a certain type of back surgery. The GCH1 gene encodes an enzyme called GTP cyclohydrolase, which is involved in folate and biopterin biosynthesis. These data suggest that inhibiting this enzyme might help to prevent or control chronic pain.