Acute pain is an essential sensory input that protects individuals from harmful environmental stimuli such as heat, extreme cold, chemical irritants, and mechanical tissue damage (803, 956). Nociception alerts us to internal threats such as infections, broken bones, and torn tendons. Without the ability to feel acute pain, there would be little stopping an individual from continuing to engage in harmful behavior. In clinical practice pain is among the most prevalent symptoms. About 20-30% of Europeans suffer at least one prolonged/chronic pain period in their life. 50-70% of them cannot be helped sufficiently due to the lack of effective drugs. In addition, currently available pain therapeutics show side effects such as nausea, dizziness, obstipation, bleeding, increased risk of arteriosclerosis, and/or drug addiction. As most of these adverse reactions limit the therapeutic use dramatically, the development of novel therapeutic drugs is urgently needed. Further, the predictability which drug is alleviating pain for which patient is low. This reflects a lack of mechanistical understanding and of mechanism-based diagnostics.