“We previously showed that in neuropathic pain, the accumulation of TNF in the brain, specifically the hippocampus, causes the dysregulation of the normal analgesic response,” said Ignatowski. “We propose that enhanced levels of TNF in the brain inhibit the release of norepinephrine. Normally, norepinephrine would activate the descending inhibitory pain pathway that projects to the spinal cord, thereby alleviating pain. But when activation of this inhibitory pathway is lost, pain may transition to a chronic state.” The new method originated with the UB researchers’ discovery in 1999 of TNF, a novel therapeutic target, specifically in the brain. They previously demonstrated that peripheral nerve injury—injury to the nerves connecting the spinal cord to the rest of the body—boosts levels of this protein in the hippocampus, a part of the brain responsible for learning and memory, and which they have recently found to be involved in the experience of chronic pain. - scienceblog.com