Why time does not heal all wounds: Chronic Pain

Pain is simultaneously an angel and a tormentor! At the heart of an expanding and dynamic area in biomedical sciences lies the question about how normal ‘pain’, which is considered a protective body function in every day life, can change into a severely debilitating chronic disease that ruins the quality of life in a large fraction of the world’s population. What happens when a physiological pain reaction turns into a self-sustained activity of the nervous system? Which molecular cascades come into play, and importantly, can this knowledge be employed to reverse pathological pain?
I would like to discuss work showing that the spinal dorsal horn, the first venue where pain-sensing incoming afferents from the periphery communicate with the central nervous system, is an important seat of functional changes that can trigger and sustain pathological pain and then go on to discuss the molecular identity of key players and their precise orchestration at spinal synapses.
Pain being an area of immense medical relevance and extraordinary socioeconomic importance, I would like to review some of our work that has directly paved the way for drug discovery. Finally, I would like to turn the spotlight on the neocortex of the brain, which can be seen as a “final frontier” in pain research, and which remains the most complex, least studied of all avenues in the pain pathway. Here, I will discuss a promising strategy based upon combining an entire arsenal on the molecular biology and neurogenetics of pain with cutting-edge methods for interrogating neural circuits, such as optogenetics, in vivo imaging across scales and electrophysiology in awake behaving mice.