New insights: chronic pain and its synaptic basis

According to a study published March 13 in the online, open-access journal PLoS Biology, researchers have discovered a novel obstruction in the pain pathway. This finding could be used to treat individuals suffering from chronic pain. Pain plays a vital role in protecting our bodies from harm. The body's skin, bones, deep tissues and viscera contain little receivers called nodiceptors that pick up harmful stimuli, which are converted into electrical signals that are transmitted to a person's brain via the spinal cord. When these nerves are persistently activated, for instance after an injury or inflammation, the information flow into the spinal cord is significantly amplified, which is known as 'synaptic long-term potentiation (LTP)'. Originally found in lower organisms, LTP is a significant biological property that evolution has conserved in humans. Led by Rohini Kuner (Heidelberg University, Germany) and Ceng Luo (Fourth Military Medical University, China), the team used genetic, physiological, biochemical, as well as behavioral tools available in mice in order to get a clearer picture of how LTP works in the context of pain signaling. After examining how LTP works at the synaptic connection between spinal cord neurons and peripheral pain sensors, the team discovered that in order for pain amplification to occur, presynaptic events that unravel in the spinal endings of pain-sensing nerves are needed. Luo, explains: "Our results indicate that an enzyme termed cGMP-activated Kinase 1 (PKG-I) is a key player in this important process." The researchers found that eliminating PKG-1 specifically from the presynaptic neurons in this pathway, destroyed LTP and changed pain-related memory and behavior. Worldwide, chronic pain is a leading cause of poor quality of life. According to recent demographic studies, 1 in every 6 Europeans experience chronic pain. Kuner, said: "Our observation that genetically silencing PKG-I, or blocking its activation, in pain-sensing nerves markedly reduced chronic inflammatory pain paves the way for potential new therapeutic approaches."