Our sensation of pain is determined by the way in which noxious stimuli are encoded by peripheral sensory nerves and then deciphered by the brain. When a stimulus like pressure or heat is strong enough to cause harm, the tiny tips of specialized sensory pain neurons generate an electrical impulse which is transmitted by the neurons from the periphery to the spinal cord and brain. Although  this is well understood in principle, scientists have long been puzzled why we can experience the same stimulus as moderate or intense pain, depending on the context in which the stimulus occurs, for example in healthy or diseased tissue. This puzzle has now been solved by elegant experiments by the Binshtok laboratory, which were published in the prestigious journal “Neuron”. The researchers developed sophisticated new imaging tools, enabling them to observe and record for the first time, how a noxious stimulus is encoded and translated to an electrical signal by a single nerve tip, one thousand times smaller than a human hair, and how this encoding changes in disease.  

Their new techniques allowed them to record the activity of peripheral pain neurons in living animals under carefully controlled conditions, showing how a stimulus evokes an electrical impulse a short distance away from the nerve fiber tip, on its way to the brain, where it is translates to the pain sensation. They discovered that the same stimulus can evoke either stronger or weaker signaling in the sensory nerve tip, which is translated to either low or high intensity pain. For example, in healthy tissue, a carefully calibrated noxious stimulus evokes an electrical signal (action potential) at some distance from the terminal tip, but when the tissue is inflamed, action potentials are generated much closer to the terminal tip, resulting in a more potent outcome. The findings suggests that the change in the place that the action potential begins can encode how the pain is experienced, and it helps to explain why pain sensitivity increases during inflammation, such that even a light touch near a sore can produce severe pain.  These findings are crucial for understanding how peripheral pain neurons process information in health and disease, and will allow scientists to develop new, more effective and specific pain treatments.