Neuroscientists have long sought to explain how recovery from an acute injury can sometimes give rise to chronic pain—and not always in the area of injury. Now, a team at the Department of Neural and Pain Sciences at the University of Maryland, Baltimore, led by Dr. Ronald Dubner, a member of TMJA’s Scientific Advisory Board, has found some intriguing clues to this mystery. They used a rat model of nerve injury, based on constricting one of the branches of the trigeminal nerve that supplies sensation to the face. Constricting the maxillary branch of the nerve results in tissue injury in the midface region followed by long-lasting hypersensitivity to pain in the area (called primary hyperalgesia). What is interesting is that the injury also induces a long-lasting hypersensitivity to pain in a nearby area of skin served by the mandibular branch of the nerve (called secondary hyperalgesia or extraterritorial hypersensitivity). Over a period of weeks, the investigators recorded the activities of nerve cells from the site of injury. And they used nerve cell and chemical transmitter blocking agents applied in the injured zone or in the brain to see how that affected pain sensitivity.
They concluded that pain signals into the brain from the local injury accounted for both the primary and secondary hyperalgesia observed in the first few days after injury. But then the brain took over to maintain secondary hyperalgesia. They found that brain cells and circuits initially activated by the pain signals from the injury now were excited and functioning in a pathway descending from the brain to maintain the secondary hyperalgesia in the zone outside the original injury. This process, described as “central nervous system modulation” is strong evidence that peripheral injury can lead to fundamental long-term changes in brain circuitry that increase sensitivity to pain. Because of the switch to central nervous system processing, there is increased sensitivity that persists at sites where there is no injury, even though the signals coming from the site of the injury have been blocked.
New classes of pain medications could emerge from the discovery. The report is the latest in a trend of scientific discoveries in animal and human studies of co-morbidity, the experience of pain in one part of the body that is associated with pain in another, discoveries that underscore an expanded role for central nervous system pathways that signal pain.